bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-semiotic resources providing maximal input in teaching science through English
Authors: Forey Gail , Polias John
Published: October 2016

This chapter addresses the role of multimodal semiotic systems in teaching science through English as a second language. We argue that pedagogical concerns should focus on language and other semiotic choices that teachers use to scaffold their students’ learning. Through an investigation of the inter-relationship of different semiotic systems (modalities), we are able to develop models of best practice that can help inform teachers. We consider two broad educational contexts: one that is becoming more prevalent, where it may happen that English is neither the primary language for the students nor for the teachers, as in Hong Kong, and one that is commonplace in places, such as Australia, where there is a large proportion of students with English as an additional language studying in a country where English is the predominant language. We use video data from two secondary science classrooms in these two contexts to analyse how the teachers provide multiple access points to meaning and how they scaffold the learners into the disciplinary literacy of science.
miRNAmeConverter: an R/bioconductor package for translating mature miRNA names to different miRBase versions
Authors: Haunsberger Stefan J , Connolly Niamh M C , Prehn Jochen H M
Published: October 2016

The miRBase database is the central and official repository for miRNAs and the current release is miRBase version 21.0. Name changes in different miRBase releases cause inconsistencies in miRNA names from version to version. When working with only a small number of miRNAs the translation can be done manually. However, with large sets of miRNAs, the necessary correction of such inconsistencies becomes burdensome and error-prone. We developed miRNAmeConverter, available as a Bioconductor R package and web interface that addresses the challenges associated with mature miRNA name inconsistencies. The main algorithm implemented enables high-throughput automatic translation of species-independent mature miRNA names to user selected miRBase versions. The web interface enables users less familiar with R to translate miRNA names given in form of a list or embedded in text and download of the results.

Availability and Implementation

The miRNAmeConverter R package is open source under the Artistic-2.0 license. It is freely available from Bioconductor (http://bioconductor.org/packages/miRNAmeConverter). The web interface is based on R Shiny and can be accessed under the URL http://www.systemsmedicineireland.ie/tools/mirna-name-converter/. The database that miRNAmeConverter depends on is provided by the annotation package miRBaseVersions.db and can be downloaded from Bioconductor (http://bioconductor.org/packages/miRBaseVersions.db). Minimum R version 3.3.0 is required.

Supplementary information

Supplementary data are available at Bioinformatics online.
Imputing gene expression to maximize platform compatibility
Authors: Zhou Weizhuang , Han Lichy , Altman Russ B
Published: October 2016

Microarray measurements of gene expression constitute a large fraction of publicly shared biological data, and are available in the Gene Expression Omnibus (GEO). Many studies use GEO data to shape hypotheses and improve statistical power. Within GEO, the Affymetrix HG-U133A and HG-U133 Plus 2.0 are the two most commonly used microarray platforms for human samples; the HG-U133 Plus 2.0 platform contains 54 220 probes and the HG-U133A array contains a proper subset (21 722 probes). When different platforms are involved, the subset of common genes is most easily compared. This approach results in the exclusion of substantial measured data and can limit downstream analysis. To predict the expression values for the genes unique to the HG-U133 Plus 2.0 platform, we constructed a series of gene expression inference models based on genes common to both platforms. Our model predicts gene expression values that are within the variability observed in controlled replicate studies and are highly correlated with measured data. Using six previously published studies, we also demonstrate the improved performance of the enlarged feature space generated by our model in downstream analysis.

Availability and Implementation

The gene inference model described in this paper is available as a R package (affyImpute), which can be downloaded at http://simtk.org/home/affyimpute.

Supplementary information

Supplementary data are available at Bioinformatics online.
Improved Clinical Efficacy with Wound Support Network Between Hospital and Home Care Service
Authors: Bergersen Tone Kristin , Storheim Elisabeth , Gundersen Stina , Kleven Linn , Johnson Maria , Sandvik Leiv , Kvaerner Kari Jorunn , Ørjasæter Nils-Otto
Published: October 2016

OBJECTIVE:

The aim of this study was to test the efficacy of a wound support network model between the primary home care service and the hospital. The impact on wound healing rate, cost benefit, and transfer of knowledge was investigated.

INTERVENTION:

The intervention group was exposed to a wound support network (n = 32), and the control group continued standard organization of treatment (n = 21).

DESIGN:

Nonrandomized controlled study; observations were made before (baseline) and after the implementation of the intervention (12 weeks).

PATIENTS:

Patients with chronic wounds (lasting >6 weeks and with wound area >1 cm2) in Oslo, Norway.

MAIN OUTCOME MEASURES:

Closure of the observation wound; wound size; total number of wounds; presence of eczema, edema, and pain; number of dressings per week; time spent per dressing; and number of control appointments at the hospital. The economic impact is calculated for the hospital and for the community of Oslo, Norway.

MAIN RESULTS:

The number of control appointments (t = 3.80, P < .001) was significantly decreased, and the number of completed treatments (P = .02) was significantly increased after 12 weeks in the intervention group compared with the control group. A significant improvement was evident in the intervention group in terms of eczema (P = .02), edema (P = .03), and closing of the observational wound (46.7% cases in the intervention group versus 25.0% in the control group).

CONCLUSIONS:

A wound support network between the primary home care service and the hospital is cost-effective, improves clinical efficacy of the home care services’ work, and reduces the need for consultations at the hospital.
Genetic association studies in osteoarthritis: is it fairytale?
Authors: Warner Sophie C. , Valdes Ana M.
Published: October 2016

Purpose of review

Osteoarthritis is a common complex disorder with a strong genetic component. Other identified risk factors such as increasing age and overweight do not fully explain the risk of osteoarthritis. Here, we highlight the main findings from genetic association studies on osteoarthritis to date.

Recent findings

Currently, genetic association studies have identified 21 independent susceptibility loci for osteoarthritis. Studies have focused on hip, knee and hand osteoarthritis, as well as posttotal joint replacement and minimum joint space width, a proxy for cartilage thickness. Four distinct loci have recently been identified in a genome-wide association scan on minimum joint space width. The role of mitochondrial DNA variants has been the focus of a recent meta-analysis. Findings have previously been mixed, however, this study suggests a plausible involvement of mitochondrial DNA in the progression of radiographic knee osteoarthritis.

Identifying genetic locations of interest provides a framework upon which to base future studies, for example replication analysis and functional work. Genetic association studies have shaped and will continue to shape research in this field. Improving the understanding of osteoarthritis could improve the diagnosis and treatment of the disease and improve quality of life for many individuals.
Dysfunction of Nucleus Accumbens Is Associated With Psychiatric Problems in Patients With Chronic Low Back Pain
Authors: Kaneko Hideaki , Zhang Shuo , Sekiguchi Miho , Nikaido Takuya , Makita Koshi , Kurata Jiro , Konno Shin-ichi
Published: October 2016

Study Design.

A cross-sectional study.

Objective.

The aim of this study was to evaluate activity of the nucleus accumbens (NAc) in response to lumbar mechanical stimulation in patients with chronic low back pain (cLBP) using functional magnetic resonance imaging (fMRI).

Summary of Background Data.

Although a modified activity of the NAc was characterized in cLBP patients, its pathological significance has yet to be determined. We hypothesized that NAc activation in response to pain might differ depending on the extent of psychiatric problems, which might be associated with the affective/motivational background of chronic pain.

Methods.

Twenty-one patients with cLBP (four men, 17 women) were recruited. Subjects were divided into two groups on the basis of scores on the patient version of the Brief Scale for Psychiatric problems in Orthopaedic Patients (BS-POP) scores: ≥17 (High Score, HiS group) and <17 (non-High Score, non-HiS group). Each subject was placed in the prone position on a 3-Tesla magnetic resonance imaging (MRI) scanner and stimulated by mechanical stimulation on the left lower back. Three blocks of 30-second pain stimulus calibrated at either 3 or 5 on an 11-grade numerical rating scale (NRS) were applied with intervening 30-second rest conditions during whole-brain echo-planar imaging. Functional images were analyzed using a multisubject general linear model with Bonferroni multiple comparisons.

Results.

Subjects in the HiS group had more intense daily pain and lower quality of life than those in the non-HiS group (P < 0.05). Catastrophic thinking in relation to pain experience did not differ between the groups. Activation at the NAc was smaller in the HiS group than in the non-HiS group (P < 0.001).

Conclusion.

The presence of psychiatric problems was associated with attenuated activity of the NAc in cLBP patients. Dysfunction of the NAc might potentially be involved in the affective/motivational factors in the chronification of LBP.

Level of Evidence. N/A
Painful Cervical Facet Joint Injury Is Accompanied by Changes in the Number of Excitatory and Inhibitory Synapses in the Superficial Dorsal Horn That Differentially Relate to Local Tissue Injury Severity
Authors: Ita Meagan E. , Crosby Nathan D. , Bulka Ben A. , Winkelstein Beth A.
Published: October 2016

Study Design.

Immunohistochemistry labeled pre- and postsynaptic structural markers to quantify excitatory and inhibitory synapses in the spinal superficial dorsal horn at 14 days after painful facet joint injury in the rat.

Objective.

The objective of this study was to investigate the relationship between pain and synapse density in the spinal cord after facet injury.

Summary of Background Data.

Neck pain is a major contributor to disability and often becomes chronic. The cervical facet joints are susceptible to loading-induced painful injury, initiating spinal central sensitization responses. Although excitatory synapse plasticity has been reported in the superficial dorsal horn early after painful facet injury, whether excitatory and/or inhibitory synapse density is altered at a time when pain is maintained is unknown.

Methods.

Rats underwent either a painful C6/C7 facet joint distraction or sham surgery. Mechanical hyperalgesia was measured and immunohistochemistry techniques for synapse quantification were used to quantify excitatory and inhibitory synapse densities in the superficial dorsal horn at day 14. Logarithmic correlation analyses evaluated whether the severity of facet injury correlated with either behavioral or synaptic outcomes.

Results.

Facet joint injury induces pain that is sustained until day 14 (P <0.001) and both significantly greater excitatory synapse density (P = 0.042) and lower inhibitory synapse density (P = 0.0029) in the superficial dorsal horn at day 14. Injury severity is significantly correlated with pain at days 1 (P = 0.0011) and 14 (P = 0.0002), but only with inhibitory, not excitatory, synapse density (P = 0.0025) at day 14.

Conclusion.

This study demonstrates a role for structural plasticity in both excitatory and inhibitory synapses in the maintenance of facet-mediated joint pain, and that altered inhibitory, but not excitatory, synapse density correlates to the severity of painful joint injury. Understanding the functional consequences of this spinal structural plasticity is critical to elucidate mechanisms of chronic joint pain.

Level of Evidence: N /A
ULTRASOUND MEASUREMENTS OF THE DISTANCE BETWEEN LIMBUS AND RETINAL BREAK IN EYES WITH MEDIA OPACITIES
Authors: Vaiano Agostino S. , Coronado Quitllet Elisabet , Zinzanella Gaetano , De Benedetti Giacomo , Caramello Guido
Published: October 2016

Purpose:

To assess the reproducibility and accuracy of ultrasound (US) measurements in determining the distance between corneoscleral limbus and retinal break and its relation with the distance measured by indirect ophthalmoscopy, in patients undergoing a laser retinopexy procedure.

Methods:

Forty-four patients with a single retinal break, scheduled for laser a retinopexy procedure (26 phakic patients and 18 pseudophakic patients), underwent 5 repeated measurements by high-resolution US and 3 measurements (at the time of the laser procedure, 1 and 3 months) by indirect ophthalmoscopy with scleral indentation of the corneoscleral limbus-retinal break distance with a caliper.

Results:

In the phakic patients group, measurements ranged from 8.75 mm to 14.45 mm (12.56 ± 1.24, mean ± SD) and from 9.5 mm to 15 mm (12.35 ± 1.32) with US and indirect ophthalmoscopy, respectively. In the pseudophakic patients group, measurements ranged from 9.04 mm to 13.95 mm (11.88 ± 1.33) and from 8.5 mm to 13.2 mm (11.93 ± 0.99) with US and indirect ophthalmoscopy, respectively. The correlation coefficient was greater than 0.97. Measurement variability was very small. In phakic eyes, it was 0.13 ± 0.08 mm and 0.13 ± 0.07 mm with US and indirect ophthalmoscopy, respectively. In pseudophakic eyes, it was 0.12 ± 0.05 mm and 0.14 ± 0.05 mm with US and indirect ophthalmoscopy, respectively. US and indirect ophthalmoscopy measurements were not statistically different (Student's t-test, P = 1.71). The analysis of the variance among phakic and pseudophakic patients confirmed that measurements of the two groups do not differ significantly (Fisher's exact test, P = 0.16). The univariate analysis showed no significant difference in both US and indirect ophthalmoscopy measurements (ANOVA, P = 0.09) and between the two types of measurements and patient groups (ANOVA, P = 0.38).

Conclusion:

This study suggests relevant accuracy and reliability of US readings and provides the possibility of using this technique for localizing tears in eyes with media opacities by identifying the meridian and corneoscleral limbus-retinal break distance.
Efficacy and Safety of Adjunctive Aripiprazole in Schizophrenia
Authors: Zheng Wei , Zheng Ying-Jun , Li Xian-Bin , Tang Yi-Lang , Wang Chuan-Yue , Xiang Ying-Qiang , de Leon Jose
Published: October 2016

This meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of adding aripiprazole to other antipsychotics in schizophrenia. A systematic computer search identified 55 RCTs including 4457 patients who were randomized to aripiprazole (14.0 ± 7.0 mg/d) versus placebo (18 RCTs) or open antipsychotic treatment (37 RCTs). Aripiprazole significantly outperformed the comparison interventions based on psychiatric scales: (1) total score in 43 RCTs (N = 3351) with a standardized mean difference (SMD) of −0.48 (95% confidence interval [CI], −0.68 to −0.28; P < 0.00001; I
2 = 88%), (2) negative symptom score in 30 RCTs (N = 2294) with an SMD of −0.61(95% CI, −0.91 to −0.31; P < 0.00001; I
2 = 91%), and (3) general psychopathology score in 13 RCTs (N = 1138) with a weighted mean difference (WMD) of −4.02 (95% CI, −7.23 to −0.81; P = 0.01; I
2 = 99%), but not in positive symptoms in 29 RCTs (N = 2223) with a SMD of −0.01 (95% CI, 0.26 to 0.25; P = 0.95; I
2 = 88%). Differences in total score based on psychiatric scales may be explained by the use of an antipsychotic for comparison rather than placebo in 31 RCTs with a nonblind design. Aripiprazole outperformed the comparison interventions for body weight in 9 RCTs (N = 505) with a WMD of −5.08 kg (95% CI, −7.14 to −3.02; P < 0.00001; I
2 = 35%) and for body mass index (BMI) in 14 RCTs (N = 809) with a WMD of −1.78 (CI: −2.25 to −1.31; P < 0.00001; I
2 = 54%). The BMI meta-regression analysis indicated aripiprazole's association with lower BMI was stronger in females. Adjunctive aripiprazole appears safe but better RCTs are needed to demonstrate efficacy. Chinese journals and scientific societies should encourage the publication of high-quality RCTs and require registration in a centralized Chinese database.
An Open-Label Pilot Study of Duloxetine in Patients With Irritable Bowel Syndrome and Comorbid Major Depressive Disorder
Authors: Lewis-Fernández Roberto , Lam Peter , Lucak Susan , Galfalvy Hanga , Jackson Elizabeth , Fried Jane , Rosario Melissa , de la Cruz Ana Alicia , Sánchez-Lacay Arturo , Díaz Samantha , Schneier Franklin
Published: October 2016

Major depressive disorder (MDD) and irritable bowel syndrome (IBS) frequently co-occur, yet treating their comorbid presentation is challenging. Low-dose tricyclic antidepressants are efficacious for IBS, but higher doses to treat depressive symptoms present tolerability problems, whereas selective serotonin reuptake inhibitors are more tolerable but show inconsistent efficacy for IBS. If efficacious, serotonin-norepinephrine reuptake inhibitors like duloxetine would provide a useful alternative. We explored efficacy, tolerability, and time to onset of action of duloxetine in comorbid IBS-MDD in an open-label, 12-week trial. Repeated-measures mixed-effects regression analysis with the intent-to-treat sample assessed rate of change of the clinician-administered Gastrointestinal Symptoms Rating Scale, Montgomery-Åsberg Depression Rating Scale, and other clinician-administered and self-report scales. Seventeen Hispanic adults with current MDD and comorbid IBS meeting Rome III criteria entered the study. Medical and laboratory assessment ruled out alarm symptoms and signs inconsistent with IBS. Duloxetine led to significant improvement in Gastrointestinal Symptoms Rating Scale and Montgomery-Åsberg Depression Rating Scale scores and 71.4% and 64.3% intent-to-treat response rates for IBS and MDD, respectively. Abdominal pain severity decreased by 56%. Contrary to expectation of rapid analgesic effects, based on duloxetine studies for neuropathic pain, both IBS and MDD symptoms improved gradually; differences in slopes of improvement were nonsignificant. Duloxetine was moderately well tolerated at a mean endpoint dose of 60 mg/d. Study limitations include the lack of placebo control, modest sample size, single ethnic group, and high attrition rate. Duloxetine efficacy for comorbid IBS-MDD should be studied under placebo-controlled conditions with larger and more diverse samples.
Dihydroxyphenylglycol as a Biomarker of Norepinephrine Transporter Inhibition by Atomoxetine
Authors: Bieck Peter R. , Leibowitz Mark , Lachno D. Richard , Ledent Edouard , Padich Robert , Jhee Stan
Published: October 2016

To assess the primary metabolite of norepinephrine, 3,4-dihydroxyphenylglycol (DHPG), as a sensitive biomarker for norepinephrine transporter (NET) function and the relationship of DHPG measured peripherally and centrally, NET was antagonized with 80 mg/d atomoxetine for 18 days. Twelve healthy subjects were treated with atomoxetine in an open-label, multiple-dose exploratory study. Plasma atomoxetine reached steady state by day 6, and the pharmacokinetic results demonstrated availability of atomoxetine to the central nervous system. The cerebrospinal fluid (CSF)/plasma ratios of atomoxetine based on area under concentration-time curve from 0 to 12 hours postdose (AUC0–12), maximum concentration (Cmax), and predose were 0.3%, 0.2%, and 11%, respectively. Plasma from atomoxetine-treated subjects (ex vivo) significantly inhibited radioligand binding to human NET (P < 0.001) only 1 hour after dosing. Plasma DHPG and DHPG/norepinephrine (ratio) during repeated posture tests were reduced significantly (P < 0.001) on day 5 and stayed significantly reduced up to 1 day after treatment. In CSF, both DHPG and the ratio were significantly reduced (P < 0.001) on day 18. Urine results showed significant decreases for both DHPG and the ratio (P = 0.010 to P < 0.001). Brain-derived neurotrophic factor in CSF was lesser than the limits of detection. The findings suggest that NET blockade can be assessed with DHPG concentration or with the ratio in plasma, CSF, and urine. The data suggest that DHPG is a useful biomarker to proactively assess the pharmacological activity of compounds intended to inhibit NET activity within the brain. The study shows that CSF is a medium for early identification and quantification of biomarkers useful in assessing novel neuroscience targets.
MRI Evidence of Neuropathic Changes in Former College Football Players
Authors: Adler Caleb M. , DelBello Melissa P. , Weber Wade , Williams Miranda , Duran Luis Rodrigo Patino , Fleck David , Boespflug Erin , Eliassen James , Strakowski Stephen M. , Divine Jon
Published: October 2016

Objective:

To examine effects of participating in collegiate football on neural health several years after retirement. We hypothesized that relative cortical thinning and loss of white matter integrity would be observed in former players.

Design:

Former NCAA Division I football players were compared with demographically similar track-and-field athletes with regard to cortical thickness and white matter integrity.

Setting:

Participants participated in MRI scans at the Center for Imaging Research at the University of Cincinnati.

Participants:

Eleven former football players and 10 demographically similar track-and-field athletes.

Main Outcome Measures:

Normalized cortical thickness was compared between groups using 2-tailed Student t test. As a secondary analysis, Spearman correlation coefficient was calculated between cortical thickness and number of concussions. Fractional anisotropy for regions-of-interest placed in frontal white matter tracts and internal capsule were compared between groups using 2-tailed Student t test.

Results:

Football players showed significantly lower cortical thickness within portions of both the frontal and temporal cortex. Affected frontal regions included left frontal pole and right superior frontal gyrus. Affected temporal regions included portions of the superior temporal gyrus, left inferior temporal gyrus, and right middle and superior temporal gyri. Cortical thickness inversely correlated with number of reported concussions over most of these regions. In addition, fractional anisotropy was lower in the right internal capsule of former football players, relative to controls.

Conclusions:

These findings suggest that at least some consequences of high-level collegiate football play persist even after the cessation of regular head blows. Longer-term studies are warranted to examine potential cognitive and functional implications of sustained cortical atrophy.
Cochlear Implantation in the Elderly: Does Age Matter?
Authors: Rohloff Katharina , Koopmann Mario , Weiß Daniel , Rudack Claudia , Savvas Eleftherios
Published: October 2016

Objective:

To compare the outcome of hearing rehabilitation in younger versus older adult cochlear implant recipients. Analysis of surgical and postoperative complications, as well as the number of auditory therapy sessions in the two age groups.

Study Design:

Individual retrospective cohort study.

Methods:

A cohort of 145 postlingually deafened adults was evaluated in this study. The patients were divided into two age groups based on the age at implantation: Group I, 18 to 69 years; and Group II, 70 and older. Postoperative hearing performance was measured based on the German Freiburg monosyllabic word test (FM) and the Oldenburg sentence test (OLSA).

Results:

Postoperative hearing evaluation results in both groups plateaued and remained constant after 12 months of implantation. The results remained constant at the 2 and 3-year time intervals. There was a significant difference in complications arising after cochlear implantation. Group II showed more cases of vertigo and dysgeusia. The number of auditory therapy sessions in both groups was similar.

Conclusion:

Cochlear implantation in the elderly is highly effective; the postoperative hearing performance is at the same level as younger adult recipients. Complex hearing tasks, such as hearing in background noise, requires an equally long time for comprehension. The recovery period of vestibular dysfunction after surgery may be longer in the elderly. Auditory therapy rehabilitation is not more time consuming in the elderly compared with the younger counterparts.
Clinical significance of the Scheuer histological staging system for primary biliary cholangitis in Japanese patients
Authors: Namisaki Tadashi , Moriya Kei , Kitade Mitsuteru , Kawaratani Hideto , Takeda Kosuke , Okura Yasushi , Takaya Hiroaki , Nishimura Norihisa , Seki Kenichiro , Kaji Kosuke , Sato Shinya , Sawada Yasuhiko , Yamao Junichi , Mitoro Akira , Uejima Masakazu , Mashitani Tsuyoshi , Shimozato Naotaka , Nakanishi Keisuke , Furukawa Masanori , Saikawa Soichiro , Kubo Takuya , Yoshiji Hitoshi
Published: October 2016

Background

Inadequate response to ursodeoxycholic acid (UDCA) is associated with unfavorable outcomes in patients with primary biliary cholangitis (PBC). We aimed to identify surrogate markers for predicting long-term prognosis and biochemical response to UDCA in patients with PBC.

Patients and methods

In this single-center, retrospective study, 99 patients with PBC were classified into responders (n=53) and nonresponders (n=46) based on reductions in the γ-glutamyl transpeptidase levels at 1 year after initiating UDCA therapy (Nara criteria). We assessed whether the criteria for patentability by different countries are useful in predicting the prognosis of PBC. The accuracy of Scheuer and Nakanuma staging systems in predicting prognosis and treatment response was compared.

Results

Nara definition had comparable utility to the Paris-II definition for selecting patients in whom UDCA monotherapy can be safely continued. Patients at Scheuer stage 1 had a significantly better prognosis than those at Scheuer stages 3 or 4 (P<0.05 and 0.0001, respectively). Patients at Nakanuma stage 4 had decreased survival compared with those at stage 1 (P<0.05). The proportion of responders to nonresponders was significantly higher in stages 1–3 PBC than in stage 4 PBC, according to both staging systems (P<0.05 for both). All patients with Scheuer stage 4 PBC were nonresponders, whereas only 28.6% (2/7) of those with Nakanuma stage 4 PBC were responders.

Conclusion

The Scheuer staging system had greater utility in predicting long-term prognosis and UDCA response than the Nakanuma staging system.
Truths and controversies concerning the role of miRNAs in atherosclerosis and lipid metabolism
Authors: Baldán Ángel , Fernández-Hernando Carlos
Published: October 2016

Purpose of review

Better tools are sorely needed for both the prevention and treatment of cardiovascular diseases, which account for more than one-third of the deaths in Western countries. MicroRNAs typically regulate the expression of several mRNAs involved in the same biological process. Therapeutic manipulation of miRNAs could restore the expression of multiple players within the same physiologic pathway, and ideally offer better curative outcomes than conventional approaches that target only one single player within the pathway. This review summarizes available studies on the prospective value of targeting miRNAs to prevent dyslipidemia and atherogenesis.

Recent findings

Silencing the expression of miRNAs that target key genes involved in lipoprotein metabolism in vivo with antisense oligonucleotides results in the expected de-repression of target mRNAs in liver and atherosclerotic plaques. However, the consequences of long-term antimiRNA treatment on both circulating lipoproteins and athero-protection are yet to be established.

A number of studies have demonstrated the efficacy of miRNA mimics and inhibitors as novel therapeutic tools for treating dyslipidemia and cardiovascular diseases. Nevertheless, concerns over unanticipated side-effects related to de-repression of additional targets should not be overlooked for miRNA-based therapies.
The Use of Routine Blood Cultures in Pediatric Appendicitis
Authors: Thompson Graham Cameron , Morrison Ellen , Ross Marshall , Liu Helena , Vanderkooi Otto G. , Eccles Robin
Published: October 2016

Objectives

To determine the proportion of true-positive blood culture results in children presenting to the ED with suspected appendicitis. To describe the current practice of obtaining blood cultures in children with suspected appendicitis.

Methods

We performed a 2-year retrospective health record review of all children aged 2 through 17 years investigated for suspected appendicitis at a tertiary Pediatric Emergency Department. Subjects were identified by searching (a) institutional records for ICD-10-CA coding, (b) diagnostic imaging records of ultrasounds for appendicitis, and (c) surgical database records for nonincidental appendectomies. Abstracted demographic and clinical data were matched to regional laboratory services data to describe the performance and result of blood cultures.

Results

Overall, 1315 children investigated for appendicitis were reviewed. Seven hundred fifty (57.0%) were girls, the average age was 11.7 years (SD, 4.0). Blood cultures were obtained in 288 (21.9%) of 1315 patients. Of the 11 (3.8%) cultures that were positive, only 1 (0.35%) was a true positive. Young age, high triage acuity, and presence of fever were associated with the acquisition of cultures (P < 0.001 for all). The proportion of children undergoing appendectomy and the negative appendectomy rate was similar between those with and without blood culture (P = 0.10 and P = 0.96, respectively).

Conclusions

True-positive blood cultures are very rare in children presenting to the ED with suspected appendicitis. Given the potential for false-positive cultures and the social/economic implications of initial testing/retesting of false positives, the use of routine blood cultures for children with suspected appendicitis is not supported.
Ex Situ Perfusion of Human Limb Allografts for 24 Hours
Authors: Werner Nicole L. , Alghanem Fares , Rakestraw Stephanie L. , Sarver Dylan C. , Nicely Bruce , Pietroski Richard E. , Lange Paul , Rudich Steven M. , Mendias Christopher L. , Rojas-Pena Alvaro , Magee John C. , Bartlett Robert H. , Ozer Kagan
Published: October 2016

Background

Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion.

Methods

Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL.

Results

Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury.

Conclusions

Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.
Atmospheric transport of trace elements and nutrients to the oceans
Authors: Jickells T. D. , Baker A. R. , Chance R.
Published: October 2016

This paper reviews atmospheric inputs of trace elements and nutrients to the oceans in the context of the GEOTRACES programme and provides new data from two Atlantic GEOTRACES cruises. We consider the deposition of nitrogen to the oceans, which is now dominated by anthropogenic emissions, the deposition of mineral dust and related trace elements, and the deposition of other trace elements which have a mixture of anthropogenic and dust sources. We then consider the solubility (as a surrogate for bioavailability) of the various elements. We consider briefly the sources, atmospheric transport and transformations of these elements and how this results in strong spatial deposition gradients. Solubility of the trace elements also varies systematically between elements, reflecting their sources and cycling, and for some trace elements there are also systematic gradients in solubility related to dust loading. Together, these effects create strong spatial gradients in the inputs of bioavailable trace elements to the oceans, and we are only just beginning to understand how these affect ocean biogeochemistry.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
Quantifying He fluxes from the mantle using multi-tracer data assimilation
Authors: Schlitzer Reiner
Published: October 2016

A global, coarse-resolution ocean model previously fitted to geostrophic shear estimates and to data of 10 hydrographic parameters and tracers has been used to simulate the
3
He and
4
He distributions resulting from the release of mantle helium from mid-ocean ridges. The model is in very good agreement with
14
C and chlorofluorocarbon data and has realistic global ocean overturning strength as well as water mass formation and transport rates. It is found that previously published global mantle
3
He fluxes are too high by a factor of about 2. In the model, optimal agreement of modelled δ
3
He with data is achieved for a global flux of 450 ± 50 mol
3
He yr
−1
. The formulation of He source strengths proportional to ridge spreading rates appears compatible with data. A model/data misfit analysis shows significant and large-scale δ
3
He underestimation in the southwestern Pacific centred over the Lau Backarc Basin (approx. 179° W/20° S). These misfits disappear in a set-up with 30 of the 450 mol yr
−1
global total
3
He flux released in the Lau Basin over a depth range between 1250 and 2500 m. Such He flux contributions are missing in present mantle He source compilations. Hydrothermal fluxes of other trace elements and isotopes (TEI) can be calculated from He fluxes on the basis of TEI : He ratios measured close to the sources.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
Diagnosing oceanic nutrient deficiency
Authors: Moore C. Mark
Published: October 2016

The supply of a range of nutrient elements to surface waters is an important driver of oceanic production and the subsequent linked cycling of the nutrients and carbon. Relative deficiencies of different nutrients with respect to biological requirements, within both surface and internal water masses, can be both a key indicator and driver of the potential for these nutrients to become limiting for the production of new organic material in the upper ocean. The availability of high-quality, full-depth and global-scale datasets on the concentrations of a wide range of both macro- and micro-nutrients produced through the international GEOTRACES programme provides the potential for estimation of multi-element deficiencies at unprecedented scales. Resultant coherent large-scale patterns in diagnosed deficiency can be linked to the interacting physical–chemical–biological processes which drive upper ocean nutrient biogeochemistry. Calculations of ranked deficiencies across multiple elements further highlight important remaining uncertainties in the stoichiometric plasticity of nutrient ratios within oceanic microbial systems and caveats with regards to linkages to upper ocean nutrient limitation.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
The oceanic budgets of nickel and zinc isotopes: the importance of sulfidic environments as illustrated by the Black Sea
Authors: Vance Derek , Little Susan H. , Archer Corey , Cameron Vyllinniskii , Andersen Morten B. , Rijkenberg Micha J. A. , Lyons Timothy W.
Published: October 2016

Isotopic data collected to date as part of the GEOTRACES and other programmes show that the oceanic dissolved pool is isotopically heavy relative to the inputs for zinc (Zn) and nickel (Ni). All Zn sinks measured until recently, and the only output yet measured for Ni, are isotopically heavier than the dissolved pool. This would require either a non-steady-state ocean or other unidentified sinks. Recently, isotopically light Zn has been measured in organic carbon-rich sediments from productive upwelling margins, providing a potential resolution of this issue, at least for Zn. However, the origin of the isotopically light sedimentary Zn signal is uncertain. Cellular uptake of isotopically light Zn followed by transfer to sediment does not appear to be a quantitatively important process. Here, we present Zn and Ni isotope data for the water column and sediments of the Black Sea. These data demonstrate that isotopically light Zn and Ni are extracted from the water column, probably through an equilibrium fractionation between different dissolved species followed by sequestration of light Zn and Ni in sulfide species to particulates and the sediment. We suggest that a similar, non-quantitative, process, operating in porewaters, explains the Zn data from organic carbon-rich sediments.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
An examination of the role of particles in oceanic mercury cycling
Authors: Lamborg Carl H. , Hammerschmidt Chad R. , Bowman Katlin L.
Published: October 2016

Recent models of global mercury (Hg) cycling have identified the downward flux of sinking particles in the ocean as a prominent Hg removal process from the ocean. At least one of these models estimates the amount of anthropogenic Hg in the ocean to be about 400 Mmol, with deep water formation and sinking fluxes representing the largest vectors by which pollutant Hg is able to penetrate the ocean interior. Using data from recent cruises to the Atlantic, we examined the dissolved and particulate partitioning of Hg in the oceanic water column as a cross-check on the hypothesis that sinking particle fluxes are important. Interestingly, these new data suggest particle-dissolved partitioning (
K
d
) that is approximately 20× greater than previous estimates, which thereby challenges certain assumptions about the scavenging and active partitioning of Hg in the ocean used in earlier models. For example, the new particle data suggest that regenerative scavenging is the most likely mechanism by which the association of Hg and particles occurs.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
Developing a test-bed for robust research governance of geoengineering: the contribution of ocean iron biogeochemistry
Authors: Boyd Philip W. , Bressac Matthieu
Published: October 2016

Geoengineering to mitigate climate change has long been proposed, but remains nebulous. Exploration of the feasibility of geoengineering first requires the development of research governance to move beyond the conceptual towards scientifically designed pilot studies. Fortuitously, 12 mesoscale (approx. 1000 km
2
) iron enrichments, funded to investigate how ocean iron biogeochemistry altered Earth's carbon cycle in the geological past, provide proxies to better understand the benefits and drawbacks of geoengineering. The utility of these iron enrichments in the geoengineering debate is enhanced by the GEOTRACES global survey. Here, we outline how GEOTRACES surveys and process studies can provide invaluable insights into geoengineering. Surveys inform key unknowns including the regional influence and magnitude of modes of iron supply, and stimulate iron biogeochemical modelling. These advances will enable quantification of interannual variability of iron supply to assess whether any future purposeful multi-year iron-fertilization meets the principle of ‘additionality’ (
sensu
Kyoto protocol). Process studies address issues including upscaling of geoengineering, and how differing iron-enrichment strategies could stimulate wide-ranging biogeochemical outcomes. In summary, the availability of databases on both mesoscale iron-enrichment studies and the GEOTRACES survey, along with modelling, policy initiatives and legislation have positioned the iron-enrichment approach as a robust multifaceted test-bed to assess proposed research into climate intervention.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
Humans and monkeys use different strategies to solve the same short-term memory tasks
Authors: Wittig John H. , Morgan Barak , Masseau Evan , Richmond Barry J.
Published: October 2016

The neural mechanisms underlying human working memory are often inferred from studies using old-world monkeys. Humans use working memory to selectively memorize important information. We recently reported that monkeys do not seem to use selective memorization under experimental conditions that are common in monkey research, but less common in human research. Here we compare the performance of humans and monkeys under the same experimental conditions. Humans selectively remember important images whereas monkeys largely rely on recency information from nonselective memorization. Working memory studies in old-world monkeys must be interpreted cautiously when making inferences about the mechanisms underlying human working memory.
Pectin Methylesterase Isoforms in Tomato (Lycopersicon esculentum) Tissues (Effects of Expression of a Pectin Methylesterase Antisense Gene)
Authors: Gaffe J. , Tieman D. M. , Handa A. K.
Published: October 2016

We have identified two major groups of pectin methylesterase (PME, EC 3.1.1.11) isoforms in various tissues of tomatoes (Lycopersicon esculentum). These two groups exhibited differential immuno-cross-reactivity with polyclonal antibodies raised against tomato fruit PME or flax callus PME and differences in their accumulation patterns in tissues of wild-type and transgenic tomato plants expressing a PME antisense gene. The group I isoforms with isoelectric points (pls) of 8.2, 8.4, and 8.5 are specific to fruit tissue, where they are the major forms of PME activity. The group II PME isoforms, with pl values of 9 and above, are observed in both vegetative and fruit tissues. The group I isoforms cross-react with polyclonal antibodies raised to a PME isoform purified from fruit, whereas the group II isoforms cross-react with antibodies to a PME purified from flax callus. Expression of a fruit-specific PME anti-sense gene impairs accumulation of the group I PME isoforms, with no apparent effect on the accumulation of the group II PME isoforms. The absence of any noticeable effects on growth and development of transgenic plants suggests that the group I PME isoforms are not involved in plant growth and development and may play a role under special circumstances such as cell separation during fruit ripening.
Water Deficit-Induced Changes in Concentrations in Proline and Some Other Amino Acids in the Phloem Sap of Alfalfa
Authors: Girousse C. , Bournoville R. , Bonnemain J. L.
Published: October 2016

Changes in amino acid composition of alfalfa (Medicago sativa L.) phloem sap were studies in response to a water deficit. Sap was collected by stylectomy. As the leaf water potential ([psi]) decreased from -0.4 to -2.0 MPa, there was significant increase of the total amino acid concentration, due to that of some amino acids: proline, valine, isoleucine, leucine, glutamic acid, aspartic acid, and threonine. Asparagine concentration, which is the main amino acid assayed in the phloem sap of alfalfa (it accounts for 70% of the total content), did not vary with the plant water status. The other amino acid concentrations remained stable as [psi] varied; in particular, [gamma]-amino butyric acid concentration remained unchanged, whereas it varied in response to wounding. The more striking change in the sieve tubes was the accumulation of proline, which was observed below a [psi] threshold value of about -0.9 MPa (concentration x60 for a decrease of [psi] from -0.9 to -2.0 MPa). The role of such changes in phloem sap amino acid concentration in osmotic adjustment of growing tissues is discussed.
Glycolytic Flux and Hexokinase Activities in Anoxic Maize Root Tips Acclimated by Hypoxic Pretreatment
Authors: Bouny J. M. , Saglio P. H.
Published: October 2016

Several enzyme activities were measured in extracts from acclimated and nonacclimated maize (Zea mays) root tips at pH 6.5 and 7.5, corresponding to cytoplasmic pH in anaerobiosis or aerobiosis, respectively, to determine what causes the decline of the glycolytic flux observed in anoxia in nonacclimated tips. We found that phosphorylation of hexoses by kinases was a major limiting step of glycolysis in anoxia. When fructose was substituted for glucose, glycolysis was slightly enhanced and survival improved, but neither matched that of acclimated tips. Decrease of kinase activities was not the result of proteolytic degradation but was more likely the result of inhibition by internal factors (low pH and low ATP). There was no evidence of induction during the hypoxic pretreatment of isoenzymes better adapted to the anoxic cellular environment. Maintenance of the glycolytic flux in acclimated tissues is explained by a combination of a rise in kinase activities and decreased inhibition resulting from a higher cytoplasmic pH and ATP content. The behavior of intact root tips is discussed in comparison with the behavior of excised root tips.
The Role of Magnesium, Pyrophosphate, and Their Complexes as Substrates and Activators of the Vacuolar H+-Pumping Inorganic Pyrophosphatase (Studies Using Ligand Protection from Covalent Inhibitors)
Authors: Gordon-Weeks R. , Steele S. H. , Leigh R. A.
Published: October 2016

Inhibitors preferentially and covalently reactive with cysteine, arginine, histidine, and carboxyl-containing residues were inhibitory to the plant vacuolar H+-transporting inorganic pyrophosphatase (H+-PPase) from Vigna radiata (mung bean) and Beta vulgaris (red beet), but hydrophobic compounds and those reactive with tyrosine and lysine were less effective. Inhibition by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, phenylglyoxal, and N-ethylmaleimide was decreased in the presence of Mg2+ or mixtures of Mg2+ and inorganic pyrophosphate (PPi) but not by PPi alone. None of these ligands affected inhibition by reagents reactive with histidine. The Mg2+ dependence of protection from 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide inhibition followed first-order kinetics and yielded a Km for free Mg2+ of 20 to 23 [mu]M. Protection from inhibition by N-ethylmaleimide and phenylglyoxal varied as a function of Mg2PPi concentration, suggesting that this is the substrate for the H+-PPase. Protection by Mg2PPi followed Michaelis-Menten kinetics with a Km of approximately 2 [mu]M. These results are consistent with the predictions of a kinetic model for the H+-PPase (R.A. Leigh, A.J. Pope, I.R. Jennings, D. Sanders [1992] Plant Physiol 100: 1698–1750), which identified free Mg2+ as an allosteric activator (Km = 25 [mu]M) and Mg2PPi as the substrate (Km = 2.5–5 [mu]M).