bluuebunny/crossref_metadata_2025 huggingface dataset:
Leydig cell genes change their expression and association with polysomes in a stage-specific manner in the adult mouse testis†,‡
Authors: Jauregui Estela J , Mitchell Debra , Garza Savanna M , Topping Traci , Hogarth Cathryn A , Griswold Michael D
Published: February 2018

Spermatogenesis in mammals occurs in a very highly organized manner within the seminiferous epithelium regulated by different cell types in the testis. Testosterone produced by Leydig cells regulates blood–testis barrier formation, meiosis, spermiogenesis, and spermiation. However, it is unknown whether Leydig cell function changes with the different stages of the seminiferous epithelium. This study utilized the WIN 18,446 and retinoic acid (RA) treatment regime combined with the RiboTag mouse methodology to synchronize male germ cell development and allow for the in vivo mapping of the Leydig cell translatome across the different stages of one cycle of the seminiferous epithelium. Using microarrays analysis, we identified 11 Leydig cell-enriched genes that were expressed in stage-specific manner such as the glucocorticoid synthesis and transport genes, Cyp21a1 and Serpina6. In addition, there were nine Leydig cell transcripts that change their association with polysomes in correlation with the different stages of the spermatogenic cycle including Egr1. Interestingly, the signal intensity of EGR1 and CYP21 varied among Leydig cells in the adult asynchronous testis. However, testosterone levels across the different stages of germ cell development did not cycle. These data show, for the first time, that Leydig cell gene expression changes in a stage-specific manner during the cycle of the seminiferous epithelium and indicate that a heterogeneous Leydig cell population exists in the adult mouse testis.
Production, mortality, and infectivity of planktonic larval sea lice, Lepeophtheirus salmonis (Krøyer, 1837): current knowledge and implications for epidemiological modelling
Authors: Brooker A J , Skern-Mauritzen R , Bron J E
Published: February 2018

Current sea louse models attempt to estimate louse burdens on wild and cultured salmon by predicting the production and distribution of lice larvae and estimating the risk of transmission. While physical characteristics of water bodies and weather can be accurately modelled, many aspects of sea lice biology require further parameterization. The aims of this review are (i) to describe current knowledge regarding the production, mortality, and infectivity of planktonic sea lice larvae and (ii) to identify gaps in knowledge and suggest research approaches to filling them. Several major gaps are identified, and those likely to have the greatest impact on infection levels are (i) egg production, viability and hatching success, (ii) predation in plankton and (iii) copepodid infectivity profiles. A key problem identified in current parameter estimates is that they originate from a number of sources and have been determined using a variety of experimental approaches. This is a barrier to the provision of “best” or consensus estimates for use in modelling. Additional and more consistent data collection and experimentation will help to fill these gaps. Furthermore, coordinated international efforts are required to generate a more complete picture of sea louse infections across all regions experiencing problems with sea lice.
A passivity-based observer for neural mass models
Authors: Liu Xian , Sun Cheng-Xia , Gao Qing , Chen Zhi-Wang
Published: February 2018

This paper presents a novel approach of designing a stabilizing observer for neural mass models which can simulate distinct rhythms in electroencephalography (EEG). Due to the structure characteristics, neural mass models are expressed as Lurie systems. The stabilizing observer is designed by using the Lurie system theory and the passive theory. The observer matrices are constructed via solutions of some linear matrix inequality (LMI) conditions. Numerical simulations are used to demonstrate the efficiency of the results.
Modular Invariant Representations of the Superconformal Algebra
Authors: Sato Ryo
Published: February 2018

We compute the modular transformation formula of the characters for a certain family of (finitely or uncountably many) simple modules over the simple $\mathcal{N}=2$ vertex operator superalgebra of central charge $c_{p,p^{\prime }}=3\left (1-\frac{2p^{\prime }}{p}\right ),$ where (p, p′) is a pair of coprime positive integers such that p ≥ 2. When p′ = 1, the formula coincides with that of the $\mathcal{N}=2$ unitary minimal series found by F. Ravanini and S.-K. Yang. In addition, we study the properties of the corresponding “modular S-matrix”, which is no longer a matrix if p′≥ 2.
Fitness cost of mcr-1-mediated polymyxin resistance in Klebsiella pneumoniae
Authors: Nang Sue C , Morris Faye C , McDonald Michael J , Han Mei-Ling , Wang Jiping , Strugnell Richard A , Velkov Tony , Li Jian
Published: February 2018

Objectives

The discovery of mobile colistin resistance mcr-1, a plasmid-borne polymyxin resistance gene, highlights the potential for widespread resistance to the last-line polymyxins. In the present study, we investigated the impact of mcr-1 acquisition on polymyxin resistance and biological fitness in Klebsiella pneumoniae.

Methods

K. pneumoniae B5055 was used as the parental strain for the construction of strains carrying vector only (pBBR1MCS-5) and mcr-1 recombinant plasmids (pmcr-1). Plasmid stability was determined by serial passaging for 10 consecutive days in antibiotic-free LB broth, followed by patching on gentamicin-containing and antibiotic-free LB agar plates. Lipid A was analysed using LC–MS. The biological fitness was examined using an in vitro competition assay analysed with flow cytometry. The in vivo fitness cost of mcr-1 was evaluated in a neutropenic mouse thigh infection model.

Results

Increased polymyxin resistance was observed following acquisition of mcr-1 in K. pneumoniae B5055. The modification of lipid A with phosphoethanolamine following mcr-1 addition was demonstrated by lipid A profiling. The plasmid stability assay revealed the instability of the plasmid after acquiring mcr-1. Reduced in vitro biological fitness and in vivo growth were observed with the mcr-1-carrying K. pneumoniae strain.

Conclusions

Although mcr-1 confers a moderate level of polymyxin resistance, it is associated with a significant biological fitness cost in K. pneumoniae. This indicates that mcr-1-mediated resistance in K. pneumoniae could be attenuated by limiting the usage of polymyxins.
Susceptibility of Fourteen New Cucurbit Species to Gummy Stem Blight Caused byStagonosporopsis citrulliUnder Field Conditions
Authors: Rennberger Gabriel , Keinath Anthony P.
Published: February 2018

At least 24 species of cucurbits from 13 genera are known to be susceptible to gummy stem blight, caused by three species of Stagonosporopsis. Cankers that are formed on crowns and stems play an important role in the disease cycle and the survival of the pathogen. Fourteen cucurbit species of unknown susceptibility representing 12 genera, four taxonomic tribes, and four geographic origins were inoculated with Stagonosporopsis citrulli in Charleston, SC, in spring 2015, spring 2016, and fall 2016 to evaluate their level of susceptibility to gummy stem blight and the ability of the pathogen to reproduce on crown cankers. An additional species, Cucumis melo, was included as a reference due to its known high susceptibility. Data sets of area under the disease progress curve (AUDPC) for foliar severity and crown cankers, final percentage of diseased leaf area, final percentage of plants with cankers, final percentage of plants with fruiting bodies, and rates of increase in canker incidence were analyzed to evaluate susceptibility. Results were similar for datasets of AUDPC and final ratings but there were more differences for AUDPC. In all experiments, Apodanthera sagittifolia, Ecballium elaterium, and Kedrostis leloja were at least as susceptible to foliar blight as the reference C. melo. K. leloja was as susceptible to crown cankers as C. melo in all experiments and A. sagittifolia and E. elaterium were among the species most susceptible to crown cankers in two experiments. Coccinia grandis was highly resistant to gummy stem blight and had a few cankers only in fall 2016. Sicana odorifera and Zehneria pallidinervia also consistently grouped with the most resistant species. Incidence of crown cankers on Cucumis melo and K. leloja increased at the fastest rate of all species in all experiments and had, along with E. elaterium, the highest incidence of crowns with fruiting bodies. In general, the most susceptible species also were most suitable for reproduction of the pathogen and had the fastest disease progression. The tribes Benincaseae and Cucurbiteae had consistently lower levels of foliar blight than Bryonieae and Coniandreae. The tribe Benincaseae had a consistently lower AUDPC for canker incidence than Bryonieae and Coniandreae. The species originating from Europe (E. elaterium) was consistently most susceptible to both symptoms, while African species grouped with the least susceptible species in all experiments. To the best of our knowledge, this is the first report of susceptibility to gummy stem blight of 14 species and the first report of susceptibility of the cucurbit tribes Coniandreae and Gomphogyneae. This expands the host range of Stagonosporopsis citrulli to 37 species representing 21 genera and seven tribes in the family Cucurbitaceae. This study demonstrates the importance of crown cankers as reproductive sites for S. citrulli.
Postpartum depression in older women
Authors: Strelow Brittany , Fellows Nicole , Fink Stephanie R. , O'Laughlin Danielle J. , Radke Gladys , Stevens Joy , Tweedy Johanna M.
Published: February 2018

Postpartum depression, which affects 10% to 20% of women in the United States, can significantly harm the health and quality of life for mother, child, and family. This article reviews the risk factors, pathophysiology, clinical manifestations, diagnosis, and treatment of postpartum depression with specific focus on women of advanced maternal age.
The emerging spectrum of exposure-related bronchiolitis
Authors: Krefft Silpa D. , Cool Carlyne D. , Rose Cecile S.
Published: February 2018

Purpose of review

Exposure-related bronchiolitis is increasingly recognized as an important but challenging clinical diagnosis. Acute and chronic inhalational exposures are associated with variable clinical presentations and a spectrum of histopathologic abnormalities affecting the small airways. This review provides an overview of the histologic patterns and occupational settings for exposure-related bronchiolitis, along with recent advances in disease diagnosis and management.

Recent findings

The entire histopathologic spectrum of bronchiolitis (constrictive, obliterative, proliferative, lymphocytic, respiratory) has been reported in exposure-related bronchiolitis. Recent studies have shown that lung clearance index testing and impulse oscillometry are more sensitive than spirometry in detecting small airways abnormalities and may augment the diagnosis of occupational bronchiolitis. Prognosis in indolent occupational bronchiolitis appears more favorable than some other types of bronchiolitis but is variable depending on the extent of bronchiolar inflammation and the stage of disease at which exposure removal occurs.

No specific histopathologic pattern of bronchiolitis is pathognomonic for occupational bronchiolitis as one or more histologic patterns may be present. A high index of suspicion is needed for exposure and disease recognition. Recent advances that may aid in diagnosis include transbronchial cryobiopsy, lung clearance index testing, and impulse oscillometry, although further research is needed.
Comparing Functional Outcomes After Injury-Specific Fixation of Posterior Malleolar Fractures and Equivalent Ligamentous Injuries in Rotational Ankle Fractures
Authors: Levack Ashley E. , Warner Stephen J. , Gausden Elizabeth B. , Helfet David L. , Lorich Dean G.
Published: February 2018

Objectives:

To evaluate the effect of posterior bony versus ligamentous injury pattern on functional outcomes in operatively treated rotational ankle fractures.

Design:

Retrospective cohort analysis of prospective registry.

Setting:

Academic Level I trauma center.

Patients/Participants:

Operatively treated supination external rotation IV and pronation external rotation IV ankle fractures.

Intervention:

Lateral malleolus plate fixation with either posterior malleolus (PM) plate fixation or posterior inferior tibiofibular ligament (PITFL) repair.

Main Outcome Measurements:

Foot and ankle outcome scores at minimum 12 months postoperatively.

Results:

One hundred seventy-eight fractures were treated with injury-specific anatomic fixation of a PM fracture (n = 122) or torn PITFL (n = 56). The PM group was significantly older, contained more women, and had lower mean body mass index versus the PITFL group. There was a higher rate of medial malleolar fracture in the PM group; other fracture and baseline characteristics were similar between groups. Univariate and multivariable analysis revealed no difference in foot and ankle outcome scores for any of the 5 summary domains (symptoms, pain, activities of daily living, sports, or quality of life) at the time of most recent follow-up. The median length of follow-up was 16.3 and 12.8 months in the PM and PITFL groups, respectively.

Conclusions:

In our cohort of ankle fractures, we have demonstrated comparable outcomes in stage IV rotational ankle fractures with and without PM fractures, indicating that the presence of a PM fracture may not result in inferior outcomes compared with ligamentous equivalent injuries if these fractures are addressed in an injury-specific manner.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Pathoanatomy of the Tongue-Type Calcaneus Fracture: Assessment Using 2- and 3-Dimensional Computed Tomography
Authors: Mitchell Phillip M. , O'Neill David E. , Gallagher Bethany , Collinge Cory A.
Published: February 2018

Objective:

To define the pathoanatomy of the tongue-type calcaneus fracture and assess the appropriateness of percutaneous techniques in addressing all planes of deformity in this injury.

Design:

Retrospective cohort.

Setting:

ACS Level I trauma center.

Patients/Participants:

Fifty-six displaced Sanders 2B and 2C tongue-type calcaneus fractures identified from an initial cohort of 1118 calcaneus fractures treated over a 16-year period.

Main Outcome Measurements:

We reviewed cross-sectional imaging and documented the presence of a varus/valgus (coronal plane) or adduction/abduction (axial plane) position of the tongue fragment in relation to the intact posterior facet, with greater than 10 degrees of angulation being diagnostic of displacement.

Results:

When assessing for displacement and angulation in the coronal plane, 98% of tongue fragments were either in a position of valgus (77%) or neutral (21%), with a mean valgus angulation of 17.3 degrees. In the axial plane, 98% of tongue pieces were in a position of adduction (64%) or neutral (34%), with an average angulation into adduction of 15.0 degrees. Sanders 2B fractures were more likely to be in a position of valgus and adduction than those of 2C fractures.

Discussion:

The tongue-type calcaneus fracture most often displaces into a position of plantarflexion, valgus, and adduction. Knowledge of this deformity may aid in achieving successful closed reduction when using the Essex-Lopresti maneuver or other less invasive techniques.
High Rate of Union for Aseptic Distal Tibial Nonunions in Adults Treated With Slow Gradual Compression via Circular External Fixation
Authors: Cunningham Bryce A. , O'Connor Daniel P. , Brinker Mark R.
Published: February 2018

Objective:

To evaluate the healing rate of aseptic nonunions of the distal third of the tibia treated with Ilizarov slow gradual compression and deformity correction.

Design:

Retrospective cohort study.

Setting:

Tertiary referral center.

Patients/Participants:

Ninety-four consecutive adult patients with 94 distal third tibial aseptic nonunions.

Intervention:

Ilizarov external fixation and slow gradual compression; most patients also underwent bone grafting, deformity correction, or both before the initiation of compression.

Main Outcome Measurements:

Rate of bony union.

Results:

Eighty-seven of 94 cases (92.6%) healed after slow gradual compression across the nonunion site with a circular external fixator. Four of the 7 patients who failed treatment healed after additional operative treatment, and the remaining 3 refused further care.

Conclusions:

Circular external fixation with slow gradual compression was successful in treating aseptic nonunions of the distal third of the tibia in 92.6% of cases. Careful selection of patients for this treatment method can lead to a high success rate with a relatively low rate of major complications.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Growth Friendly Surgery and Serial Cast Correction in the Treatment of Early-onset Scoliosis for Patients With Prader-Willi Syndrome
Authors: Oore Jonathan , Connell Braydon , Yaszay Burt , Samdani Amer , Hilaire Tricia St. , Flynn Tara , El-Hawary Ron
Published: February 2018

Background:

Prader-Willi syndrome (PWS) patients can present with scoliosis which can be treated with serial cast correction (SCC) or with growth friendly surgery (GFS). This study’s purpose was to describe the results of SCC as well as GFS for PWS patients with early-onset scoliosis (EOS).

Methods:

PWS patients were identified from 2 international multicenter EOS databases. Scoliosis, kyphosis, spine height (T1-S1), right/left hemithoracic heights/widths (RHTH, LHTH, RHTW, LHTW) were measured pretreatment, postoperation, and at 2-year follow-up. Complications were recorded.

Results:

Overall, 23 patients with 2-year follow-up were identified. Pretreatment; patients treated with SCC (n=10) had mean age of 1.8±0.6 years; body mass index (BMI), 16±1.5 kg/m2; scoliosis, 45±18 degrees; kyphosis, 56±9 degrees; T1-S1, 22.4±2.4 cm; RHTH, 8.0±2.0 cm; LHTH, 8.5±1.7 cm; RHTW, 6.6±1.3 cm; and LHTW, 8.0±1.0 cm. Patients treated with GFS (n=13) had mean age of 5.8±2.6 years; BMI, 21±5.4 kg/m2; scoliosis, 76±14 degrees; kyphosis, 59±25 degrees; T1-S1, 24.1±3.6 cm; RHTH, 10.0±1.6 cm; LHTH, 10.6±1.6 cm; RHTW, 9.4±2.5 cm; and LHTW, 8.1±2.8 cm. At 2-year follow-up, patients treated with SCC had mean scoliosis 37±11 degrees (18% correction, P=0.06); kyphosis, 42±6 degrees (NS); T1-S1, 26.4±2.1 cm (P<0.01); RHTH, 9.0±1.1 cm (13%; P=0.30); LHTH, 10.0±1.5 cm (18%, P<0.01); RHTW, 7.4±1.1 cm (12%, P<0.01); and LHTW, 8.0±1.0 cm (0%, P=0.34). At 2-year follow-up, patients treated with GFS had mean scoliosis 42±13 degrees (45% correction, P<0.000001); kyphosis, 53±13 degrees (10%, P=0.19); T1-S1, 31.5±5.4 cm (P<0.00001); RHTH, 12.0±2.4 cm (20%; P<0.01); LHTH, 12.0±1.7 cm (13%; P<0.01); RHTW, 9.8±1.3 cm (4%; P=0.27); and LHTW, 7.9±2.3 cm (3%;P=0.11). As an entire group, patients with a BMI>17 kg/m² had more device-related than disease-related complications (P=0.09). Patients treated with SCC had 0.9 complications per patient. Patients treated with GFS had 2.2 complications per patient [≤5 y more often had ≥2 complications (P=0.05)].

Conclusions:

At 2-year follow-up, SCC and GFS were both effective in treating EOS in PWS patients. Patients treated with SCC had significant improvements in spine height and LHTH. Patients treated with GFS had significant improvements in scoliosis magnitude, spine height, RHTH, and LHTH.

Level of Evidence:

Level IV—therapeutic study.
The Association Between Acute Respiratory Distress Syndrome Hospital Case Volume and Mortality in a U.S. Cohort, 2002–2011*
Authors: Ike John D. , Kempker Jordan A. , Kramer Michael R. , Martin Greg S.
Published: February 2018

Objectives:

This study examines the relationships between hospitals’ annual acute respiratory distress syndrome case volume with hospitals’ acute respiratory distress syndrome case fatality rates and individuals’ odds of acute respiratory distress syndrome hospital mortality.

Design:

Retrospective cohort study.

Setting:

The U.S. Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample, 2002–2011.

Patients:

Acute respiratory distress syndrome discharges defined by the presence of an acute respiratory distress syndrome International Classification of Diseases, 9th revision, Clinical Modification diagnosis code (518.82 or 518.5) and a mechanical ventilation procedure code (96.70, 96.71 or 96.72) on the discharge diagnosis and procedure lists. If the procedure code 96.71 was on the discharge record (mechanical ventilation < 96 hr duration), the patient also needed to be classified as deceased.

Interventions:

None.

Measurements and Main Results:

We analyzed 2,686 hospitals and 117,204 cases of acute respiratory distress syndrome. Average annual hospital acute respiratory distress syndrome in-hospital mortality was 47%. Acute respiratory distress syndrome case volume was categorized as low (1–9), medium (10–49), and high (50–423 cases per year). In a hospital-level Poisson regression adjusting for hospital characteristics, when compared with low-volume acute respiratory distress syndrome hospitals, high- and medium-volume acute respiratory distress syndrome hospitals had lower annual acute respiratory distress syndrome case fatality (rate ratio, 0.75; 99% CI, 0.71–0.79 and rate ratio, 0.86; 99% CI, 0.82–0.90, respectively; p ≤ 0.001 for both). In an individual-level, multivariable model adjusting for hospital and individual characteristics, high and medium acute respiratory distress syndrome volume hospitals were associated with lower odds of acute respiratory distress syndrome mortality compared with low-volume hospitals (odds ratio, 0.85 [99% CI, 0.74–0.99]; p = 0.006 and odds ratio, 0.89 [99% CI 0.79–1.00]; p = 0.01, respectively).

Conclusions:

In this cohort, at both an individual- and hospital-level, higher acute respiratory distress syndrome hospital case volume is associated with lower acute respiratory distress syndrome hospital mortality.
Cerebral Autoregulation in the Prediction of Delayed Cerebral Ischemia and Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients*
Authors: Gaasch Max , Schiefecker Alois J. , Kofler Mario , Beer Ronny , Rass Verena , Pfausler Bettina , Thomé Claudius , Schmutzhard Erich , Helbok Raimund
Published: February 2018

Objectives:

Pressure reactivity index and oxygen reactivity index are used to assess cerebral autoregulation after acute brain injury. The value of autoregulation indices in the prediction of delayed cerebral ischemia and outcome in patients with subarachnoid hemorrhage is still inconclusive. In this study, we aimed to focus on the predictive value of the first 72 hours commonly referred to as “early brain injury” in comparison to the overall monitoring period.

Design:

Retrospective observational cohort study.

Setting:

Neurocritical care unit at a tertiary academic medical center.

Patients:

Forty-three consecutive poor-grade patients with nontraumatic subarachnoid hemorrhage admitted between 2012 and 2016 undergoing continuous high-frequency monitoring.

Interventions:

High-frequency monitoring includes arterial blood pressure, intracranial pressure, and brain tissue oxygen tension. Pressure reactivity index and oxygen reactivity index were evaluated as moving correlation coefficient between mean arterial pressure/intracranial pressure and cerebral perfusion pressure/brain tissue oxygen tension, respectively.

Measurements and Main Results:

Median autoregulation monitoring time was 188 ± 91 hours per patient. Initial pressure reactivity index was 0.31 ± 0.02 and decreased significantly to 0.01 ± 0.01 (p < 0.001) 3 days after admission with a second peak 10 days after admission (0.18 ± 0.14; p = 0.001). Admission oxygen reactivity index was high, 0.25 ± 0.03, and decreased to a minimum of 0.11 ± 0.02 eight days after admission (p = 0.008). Patients with delayed cerebral ischemia had significantly higher overall mean pressure reactivity index values (p < 0.04), which were more pronounced during the first 72 hours, reflecting early brain injury (p < 0.02). High pressure reactivity index during the first 72 hours was associated with poor functional outcome (p < 0.001). No association between oxygen reactivity index and delayed cerebral ischemia or clinical outcome was observed (p = 0.8/0.78).

Conclusions:

High initial pressure reactivity index, presumably reflecting early brain injury, but not oxygen reactivity index, was associated with delayed cerebral ischemia and worse clinical outcome in poor-grade subarachnoid hemorrhage patients. Our data indicate that autoregulation indices should be interpreted cautiously when used in these patients and that timing is crucial when autoregulation indices are evaluated as predictor for delayed cerebral ischemia and outcome.
HMGN2: An Antitumor Effector Molecule of γδT Cells
Authors: Chen Jiao , Fan Yaping , Cui Bomiao , Li Xiaoying , Yu Yu , Du Yue , Chen Qianming , Feng Yun , Zhang Ping
Published: February 2018

γδT cells function in the regulation of T-cell activation in cancer and have been identified as a novel target for cancer immunotherapy. Activated γδT cells release a series of cytotoxic molecules-including granulysin, perforin, Fas/Fas ligand (Fas-L), and granzymes A and B-to kill target cells. Our previous research has shown that high mobility group nucleosomal-binding domain 2 (HMGN2), which is expressed at a high level in activated CD8+T cells, is an antitumor effector molecule of CD8+T cells. In the present study, we examined the expression and antitumor effects of HMGN2 in γδT cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors with a PBMC separation column. PMBCs were stimulated with isopentenyl pyrophosphate (IPP) and interleukin-2 (IL-2) for 10 days for activation and expansion. Activated γδT cells were isolated from IPP-pretreated PBMCs with a Moflo XDP flow cytometry sorter. The expression of HMGN2 in γδT cells was detected by flow cytometry and enzyme-linked immunosorbent assay. The cytotoxic effects of γδT cells and HMGN2 were analyzed by carboxyfluorescein succinimidyl ester labeling. IPP combined with IL-2 induced significant activation and expansion of γδT cells in vitro. HMGN2 was constitutively expressed in γδT cells. IPP-activated γδT cells expressed a high level of HMGN2 that could be detected intracellularly and in the supernatant. Moreover, supernatants of purified γδT cells were sufficient to kill tumor cells and could be blocked with anti-human HMGN2 antibody. This study suggests that HMGN2 is an antitumor effector molecule of γδT cells.
The Risk of Diarrhea and Colitis in Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis
Authors: Tandon Parul , Bourassa-Blanchette Samuel , Bishay Kirles , Parlow Simon , Laurie Scott A. , McCurdy Jeffrey D.
Published: February 2018

Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti–programmed death-1 (PD-1) or anti–cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis. Pooled incidence and weighted relative risk estimates with 95% confidence intervals (CI) were estimated using random effects model. Eighteen studies were included: 6 studies (1537 patients) with PD-1 inhibitors and 15 studies (3116 patients) with CTLA-4 inhibitors. The incidence of all-grade diarrhea was 13.7% (95% CI, 10.1%–17.2%) for anti-PD-1 and 35.4% (95% CI, 30.4%–40.5%) for anti-CTLA-4. The incidence of all-grade colitis was 1.6% (95% CI, 0.7%–2.4%) for anti-PD-1, and 8.8% (95% CI, 6.1%–11.5%) for anti-CTLA-4. When PD-1 inhibitors were compared directly with CTLA-4 inhibitors, the relative risk of all-grade diarrhea was 0.58 (95% CI, 0.43–0.77), and the relative risk of all-grade colitis was 0.16 (95% CI, 0.05–0.51). The rate of therapy discontinuation was numerically higher for anti-CTLA-4 therapy compared with anti-PD-1 therapy. Finally, 2 studies compared combination immunotherapy with anti-CTLA-4 therapy alone. The relative risk of developing all-grade diarrhea and colitis with combination therapy was 1.31 (95% CI, 1.09–1.57) and 1.21 (95% CI, 0.73–1.99), respectively. Diarrhea and colitis are frequent toxicities associated with checkpoint inhibitors, and seem to be most common with CTLA-4 inhibitors.
“Meniscus Sign” to Identify the Lenticule Edge in Small-Incision Lenticule Extraction
Authors: Titiyal Jeewan S. , Kaur Manpreet , Brar Anand S. , Falera Ruchita
Published: February 2018

Purpose:

To describe our technique of lenticule edge identification in small-incision lenticule extraction using the “meniscus sign” to prevent lenticule misdissection.

Methods:

Femtosecond laser application for small-incision lenticule extraction was performed. A “double ring” was visible, signifying the edge of the cap cut (outer ring) and lenticule cut (inner ring). The anterior and posterior lamellar planes were delineated in 2 different directions. During creation of the posterior lamellar channel, the lenticule edge was slightly pushed away from the surgeon to create a gap between the inner ring (diameter of the lenticule cut) and the lenticule edge. The lenticule edge assumed a frilled wavy appearance, and the meniscus sign was observed as a gap between the lenticule edge and the inner ring. The meniscus-shaped gap served as a landmark to identify the lenticule edge, and the relationship between the frilled lenticule edge and surgical instruments further acted as a guide to identify the correct plane of dissection.

Results:

This technique was successfully undertaken in 50 eyes of 25 patients. The meniscus sign was observed in all cases, and no case had cap lenticular adhesions.

Conclusions:

The meniscus sign helps to identify the lenticule edge and correct dissection planes and provides a visual landmark during the entire surgical procedure.
The Relationship Between Difficulties in Daily Living and Suicidal Ideation Among Older Adults
Authors: Zhang Li , Sun Long , Zhou Chengchao , Ge Dandan , Qian Yangyang
Published: February 2018

To date, few studies have examined the association between difficulties in activities of daily living (ADL) and suicidal ideation (SI) among the seniors in China. This study aims to explore this association among older adults in China. A total of 3313 older people (60+) were included in this study, and questionnaires were administered by face-to-face interview. In total, 4.2% of the participants reported SI. The mean score of ADL among older adults with SI (21.06 ± 10.92) was much higher than that in those without SI (16.13 ± 5.60). Multivariate analyses showed that some specific domains of ADL including using transport, medical care, and household activities were associated with SI even after we controlled the psychological conditions. An association was observed between difficulties in daily living and SI among older adults in China. Psychological interventions should be taken to prevent potential risk of suicide targeting the seniors with certain disabilities.
Low-grade Endometrioid Stromal Sarcoma of the Paratestis
Authors: Agaimy Abbas , Moskalev Evgeny A. , Weisser Wera , Bach Thorsten , Haller Florian , Hartmann Arndt
Published: February 2018

Tumors with Müllerian-like serous or mucinous phenotypes originating in the testis and its adnexa are rare neoplasms that have been increasingly recognized in recent years. Cystadenomas with or without ovarian-type stroma, borderline tumors, and adenocarcinomas are the main documented types. Although a handful cases of putative endometrioid adenocarcinomas have been reported, to our knowledge no case of endometrial stromal-type neoplasm has ever been reported in the literature. A 59-year-old man presented with a 2 cm left intrascrotal mass that was found on sonographic examination to arise from the epididymal tail with prominent vascularization. He was otherwise healthy without significant clinical history, endocrinopathy, or external hormone therapy. His testicular tumor markers (beta-HCG, AFP) were normal. Histologic examination of the resection showed a multinodular tumor closely associated with the epididymis and composed of monotonous rounded to ovoid cells with scanty cytoplasm and prominent spiral-like arterioles and capillaries. Mitotic activity was high. No other tumor component was seen. Immunohistochemistry revealed strong and diffuse expression of vimentin, CD10, estrogen receptor, and progesterone receptor. Molecular examination (performed on paraffin-embedded tumor tissue using a 517 gene fusion next-generation sequencing assay) showed a JAZF1/SUZ12 translocation, which was then confirmed by fluorescence in situ hybridization (FISH). These findings are consistent with a low-grade endometrioid stromal sarcoma originating in the paratestis. This report represents a novel addition to the growing spectrum of Müllerian-analog testicular adnexal neoplasms.
Beneficial Effects of Adrenal Androgen Supplement in Bleeding Cirrhotic Rats
Authors: Huang Hui-Chun , Hsu Shao-Jung , Chang Ching-Chih , Tsai Ming-Hung , Lee Fa-Yauh , Hou Ming-Chih , Lee Shou-Dong
Published: February 2018

Critical illness is accompanied by hypothalamic-pituitary-adrenal axis activation, but adrenal insufficiency characterized by inadequate glucocorticoid synthesis is common in critically ill cirrhotic patients, the “hepato-adrenal syndrome.” Adrenal cortex also synthesizes androgen (dehydroepiandrosterone, DHEA). DHEA maintains microcirculation by enhancing vascular endothelial nitric oxide synthase (eNOS) activity. In critical patients of other disease entities, a shift of adrenal steroidogenesis away from androgens toward glucocorticoid has been noted, arousing interests in androgen replacement in critical settings. Nevertheless, this has not been surveyed in cirrhosis with hemorrhage. In this study, liver cirrhosis was induced with common bile duct ligation (BDL) in Spraque-Dawley rats. Sham rats were controls. DHEA or vehicle was injected at the beginning of hemorrhage-transfused procedure, followed by terlipressin injection. Hemodynamic parameters were measured. Then abdominal aorta, superior mesenteric arteries (SMA) and splenorenal shunt (prominent portosystemic collateral vessel in rodents) eNOS and inducible NOS protein expressions were evaluated. In bleeding BDL groups without terlipressin injection, adrenocorticotropic hormone (ACTH) stimulation test was performed to evaluate the DHEA response. The results showed that DHEA significantly elevated mean arterial pressure, cardiac output, and stroke volume of bleeding cirrhotic rats treated with terlipressin and reduced systemic vascular resistance without affecting SMA flow, resistance, and portal pressure. DHEA upregulated abdominal aorta and SMA eNOS expressions. ACTH did not stimulate DHEA synthesis in bleeding BDL rats. In conclusion, androgen deficiency exists in bleeding cirrhotic rats. DHEA augments terlipressin-induced amelioration of shock without influencing splanchnic hemodynamics, possibly rendering it a feasible adjunct to vasoconstrictors in variceal hemorrhage.
Plasmodium–Salmonella Coinfection Induces Intense Inflammatory Response, Oxidative Stress, and Liver Damage: A Mice Model Study for Therapeutic Strategy
Authors: Patel Dinesh K. , Mittal Sandeep , Tiwari Nimisha , Maurya Anil K. , Singh Dhirendra , Pandey Alok K. , Pal Anirban
Published: February 2018

Impairment of host immune response in malaria favors bacteremia caused by typhoidal or nontyphoidal serovars of Salmonella enterica. Ofloxacin and Artesunate are the drugs that are clinically proven for treating typhoid and malaria, respectively. The study evaluates the host responses upon treatment with antibiotic (Ofloxacin) and antimalarial (Artesunate) in a standardized mice model harboring coinfection. BALB/c mice (18–22 g) were simultaneously coinfected with Plasmodium yoelii nigeriensis (Pyn) and S. enterica serovar Typhimurium (STm) and then treated with Ofloxacin or/and Artesunate from day 4 to day 7. The bacterial burden, liver function enzymes, oxidative stress, m-RNA expression of Toll-like receptors (TLR-2 and TLR-4), Th1/Th2 cytokines, hemeoxygenase-1, and NFкB were assessed. Ofloxacin treatment failed to counter the bacterial proliferation in Pyn-STm coinfected mice. However, upon controlling parasitemia with antimalarial, the efficacy of Ofloxacin could be regained. Elevated bacterial burden with malaria induces the expression of TLR-2 and TLR-4 triggering intense inflammatory response (NFκB, Th1/Th2 cytokines) in coinfected mice. This results in critical liver damage (ALT, AST, and ALP), oxidative stress (lipid peroxidation, total GSH, catalase, and super oxide dismutase), and hemeoxygenase-1 (HO-1). The study concludes that malaria infection aggravates the secondary infection of Salmonella serovars and the control of septicemia is critical in recovery of the coinfected subject.
Outcomes With Overlapping Surgery at a Large Academic Medical Center
Authors: Ponce Brent A. , Wills Bradley W. , Hudson Parke W. , Huntley Samuel R. , Starnes Austin C. , Watson Shawna L. , Rue Loring W. , Perez Jorge L. , McGwin Gerald
Published: February 2018

Objective:

The aim of the study was to evaluate the efficiency and safety of overlapping surgery (OS) at a training institution by comparing it with nonoverlapping surgery (NO) with respect to operative time, mortality, readmissions, and complications.

Background:

OS is the practice of an attending physician providing supervision to 2 surgeries that are scheduled at overlapping times. Recent media and government attention have raised concerns about this practice and the need for informed patient consent.

Methods:

A population-based, retrospective, cohort study was conducted using data on operative procedures from January 1, 2014 to December 31, 2015 at a large tertiary academic center. Patients who had undergone surgery by attending surgeons who performed ≥10% of their cases overlapping were selected. Thirty-day mortality, readmission within 30 days, and 7 patient safety indicators (PSIs) were recorded.

Results:

A total of 26,260 cases met our criteria for analysis for surgical time and 15,106 cases for outcomes. OS patients had an average case length of 2.18 hours compared with 1.64 hours among NO patients (P < 0.0001), a decreased risk of mortality [relative risk (RR) 0.42, 95% confidence interval (CI), 0.34–0.52, P < 0.0001), a decreased risk of readmission (RR 0.92, 95% CI, 0.86–0.98, P = 0.0148), and a decreased risk of experiencing any PSI (RR 0.67, 95% CI, 0.55–0.83, P = 0.0002).

Conclusions:

The present study confirms prior reports and addresses gaps in the literature regarding OS, such as the effect of resident involvement and the individual effect of OS in 13 different surgical specialties. The findings highlight the need for additional investigation and suggest that the practice of OS does not expose patients to increased risk of negative outcomes.
The effect of product line endpoint prices on vertical extensions
Authors: Pontes Nicolas Gonçalves
Published: February 2018

Purpose

Literature in brand extensions has relied greatly on categorization theory and on prototypical models of categorization to explain the affect transfer from a parent brand to its extensions. Drawing on the range theory exemplar models of categorization, this paper aims to show the effects of parent brand endpoint prices on consumer judgments of vertical line extensions.

Design/methodology/approach

Three experiments have been conducted. Experiment 1 tests the hypothesis that consumers rely on the parent brand price range when making judgments of an upscale extension. Experiment 2 tests the hypothesis that the effect of price range on extension evaluation is mediated by perceived risks for upscale extensions but not downscale extensions. The final experiment shows a boundary condition to the product line range effect on upscale extensions.

Findings

This research shows that upscale extensions are judged more favorably in the context of a wide versus a narrow product line even when the highest endpoints in both product lines are equally close to the extension and that this effect is mediated by perceived consistency and perceived risk. The range effect disappears, however, when consumers have a broad focus in which attention shifts to category endpoint prices, making parent brand prices less diagnostic of upscale extension judgments.

Practical implications

Managers may display a wider range of products and/or reduce prices of low-end models to expand product line price width. In consequence, low-end products become more competitive in terms of price and at the same time improve favorability ratings of the new upscale product.

Originality/value

Vertical line extensions and product line pricing are important topics to both academics and practitioners. Nonetheless, this is the first research to demonstrate how product line price width can influence consumer perceptions of vertical line extensions.
Antecedents and outcomes of brand love: utilitarian and symbolic brand qualities
Authors: Bairrada Cristela Maia , Coelho Filipe , Coelho Arnaldo
Published: February 2018

Purpose

Brand love is associated with consumer behaviours that are key for organisational performance. However, research on the antecedents of brand love is sparse. The current research draws on the information processing model as well as on the experiential approaches to consumer behaviour to develop a model comprising a novel set of antecedents.

Design/methodology/approach

To test the research hypotheses, we resort to two samples, which implied the collection of usable 1,018 questionnaires. For hypotheses testing, we resort to structural equation modelling.

Findings

Both functional constructs as well as more symbolic/emotional ones are positively associated with brand love. In addition, constructs with a more functional nature tend to have an indirect effect on brand love, whereas constructs with a higher level of abstraction tend to mediate the effects of more specific brand qualities. Finally, brand love is related with important outcomes, including loyalty, word of mouth and willingness to pay a premium price.

Research/limitations implications

This research has a cross-sectional nature. Moreover, we rely on a single informant, but the procedural remedies as well as the statistical tests we conducted suggest that common method variance is not a concern.

Practical implications

The findings suggest that managers should emphasise both functional as well as emotional/symbolic aspects to strengthen the links between brands and consumers, which will be beneficial for both sides.

Originality/value

This study is the first to investigate the relationship between a number of symbolic and functional brand aspects and the development of brand love feelings.
Calculation and analysis of energy consumption of Chinese national rail transport
Authors: Liu Jiangwei
Published: February 2018

Purpose

The rail transport sector in China represents one of the largest consumers of energy today, and the primary purpose of this paper is to examine the causes of changes in energy consumption of Chinese national rail transport (ECCNRT).

Design/methodology/approach

For this study, reasonable indicators as factors that affected conversion volume (CV) and unit energy consumption (UEC) based on statistical data from 1990 to 2010 were selected. CV and UEC models were established by regression analysis and tested using real data of 2011-2014. The CV model indicates it has an exponential relationship with GDP. Besides, there is a quantitative relationship between UEC and the quantity of locomotives. The ECCNRT calculation model was proposed and ECCNRT model data were compared with the real data. Impacts of different factors on ECCNRT were analyzed with economic principles.

Findings

The analysis conducted shows that the calculation model can reflect variation of ECCNRT precisely, and ECCNRT has a quantitative relation with GDP and quantities of locomotives. GDP accounts for changes of ECCNRT 20.02 per cent, while those for quantity of diesel locomotives and electric locomotives are 26.87 and 53.11 per cent, respectively. The number of electric locomotives is the main factor that influences variation of ECCNRT.

Originality/value

Through regression analysis, this study discovered the inner quantitative relationship between the conversion volume (important index of Chinese national rail transport production) and GDP. In addition, this study establishes the ECCNRT model according to the Chinese national rail transport data, which can be used to calculate the amount of ECCNRT and conduct quantitative analysis for different impacts of various factors on ECCNRT’s changes.
Client orientation of central power generation companies
Authors: Fedosova Alina , Volkova Irina
Published: February 2018

Purpose

This paper aims to identify the effects of client orientation on the business models of central power generation companies.

Design/methodology/approach

Five major Russian wholesale electricity market players have been selected for the analysis conducted by applying the “business model canvas”. To identify the changes induced by client orientation, the progress of companies’ business models has been traced over six years, from 2009 to 2015.

Findings

Five major trends in business model changes because of client orientation have been identified: declaration of the movement toward client orientation and adoption of client service standards; emergence of business diversification in favour of engineering, construction, service, operation and maintenance of power-generating facilities; increase in vertical integration; increase in the diversity of communication channels with consumers; and increase in the diversity of customer relationships. The results have been compared with those obtained from international studies. The conclusions about international and local characters of the trends are presented.

Originality/value

The study contributes to the knowledge of the current and upcoming changes in the business of central power generation companies triggered by the advent of electricity prosumers. The results are valuable for both management decision makers and theorists.