bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary structure model of the naked segment 7 influenza A virus genomic RNA
Authors: Ruszkowska Agnieszka , Lenartowicz Elzbieta , Moss Walter N. , Kierzek Ryszard , Kierzek Elzbieta
Published: October 2016

The influenza A virus (IAV) genome comprises eight negative-sense viral (v)RNA segments. The seventh segment of the genome encodes two essential viral proteins and is specifically packaged alongside the other seven vRNAs. To gain insights into the possible roles of RNA structure both within and without virions, a secondary structure model of a naked (protein-free) segment 7 vRNA (vRNA7) has been determined using chemical mapping and thermodynamic energy minimization. The proposed structure model was validated using microarray mapping, RNase H cleavage and comparative sequence analysis. Additionally, the detailed structures of three vRNA7 fragment constructs — comprising independently folded subdomains — were determined. Much of the proposed vRNA7 structure is preserved between IAV strains, suggesting their importance in the influenza replication cycle. Possible structure rearrangements, which allow or preclude long-range RNA interactions, are also proposed.
The topogenic function of S4 promotes membrane insertion of the voltage-sensor domain in the KvAP channel
Authors: Mishima Eriko , Sato Yoko , Nanatani Kei , Hoshi Naomi , Lee Jong-Kook , Schiller Nina , von Heijne Gunnar , Sakaguchi Masao , Uozumi Nobuyuki
Published: October 2016

Voltage-dependent K+ (KV) channels control K+ permeability in response to shifts in the membrane potential. Voltage sensing in KV channels is mediated by the positively charged transmembrane domain S4. The best-characterized KV channel, KvAP, lacks the distinct hydrophilic region corresponding to the S3–S4 extracellular loop that is found in other K+ channels. In the present study, we evaluated the topogenic properties of the transmembrane regions within the voltage-sensing domain in KvAP. S3 had low membrane insertion activity, whereas S4 possessed a unique type-I signal anchor (SA-I) function, which enabled it to insert into the membrane by itself. S4 was also found to function as a stop-transfer signal for retention in the membrane. The length and structural nature of the extracellular S3–S4 loop affected the membrane insertion of S3 and S4, suggesting that S3 membrane insertion was dependent on S4. Replacement of charged residues within the transmembrane regions with residues of opposite charge revealed that Asp72 in S2 and Glu93 in S3 contributed to membrane insertion of S3 and S4, and increased the stability of S4 in the membrane. These results indicate that the SA-I function of S4, unique among K+ channels studied to date, promotes the insertion of S3 into the membrane, and that the charged residues essential for voltage sensing contribute to the membrane-insertion of the voltage sensor domain in KvAP.
In vitro germ cell differentiation from embryonic stem cells of mice: induction control by BMP4 signalling
Authors: Makoolati Zohreh , Movahedin Mansoureh , Forouzandeh-Moghadam Mehdi
Published: October 2016

The present study aims to confirm and analyse germ cell-related patterns and specific gene expressions at a very early stage of cell commitment. Following the XY cytogenetic confirmation of the CCE mouse embryonic stem cells (mESCs) line, cells were cultured to form embryoid bodies (EBs). Expression pattern assessment of the mouse vasa homologue (Mvh), Stra8, α6 and β1 integrin genes in ESC and 1–3-day-old EB showed that all genes except α6 integrin were expressed in the ESC. The mean calibration of Mvh, Stra8 and α6 integrin expression significantly increased upon EB formation compared with the ESCs. During mouse embryogenesis, the signalling of bone morphogenetic protein (BMP) is essential for germ-line formation. To investigate its role in germ-line induction in vitro, mESCs were cultured as 1-day-old EB aggregates with BMP4 for 4 days in STO co-culture systems, in the presence and absence of 5 ng/ml BMP4. At the end of the culture period, colony assay (number and diameter) was performed and the viability percentage and proliferation rate was determined. There were no significant statistical differences in the abovementioned criteria between these two groups. Moreover, the expression of Mvh, α6 and β1 integrins, Stra8 and Piwil2 genes was evaluated in co-culture groups. The molecular results of co-culture groups showed higher–but insignificant–Piwil2 and significant α6 integrin expressions in BMP4 treated co-culture systems. These results confirmed that the EB system and the presence of BMP4 in a STO co-culture system improve the differentiation of ESCs to germ cell.
Modified Elmslie–Trillat Procedure for Recurrent Dislocation of the Patella
Authors: Mitani Genya , Maeda Takashi , Takagaki Tomonori , Hamahashi Kosuke , Serigano Kenji , Nakamura Yutaka , Mochida Joji , Sato Masato
Published: October 2016

Many groups have reported good to excellent clinical outcomes of the Elmslie–Trillat (ET) procedure for recurrent dislocation of the patella. However, the mean follow-up period of these studies was no more than 5 years. We hypothesized that the long-term postoperative outcomes of the modified ET procedure for recurrent dislocation of the patella would be acceptable compared with those of other procedures. The long-term postoperative outcomes of patients treated with the modified ET procedure were examined. A total of 31 knees in 27 patients with recurrent dislocation of the patella who underwent a modified ET procedure (without medial capsular plication) were evaluated. The mean follow-up period was 13.0 years. Pre- and postoperative radiographs were examined to determine the Q-angle, tilting angle, lateral shift ratio, sulcus angle, congruence angle, and Insall–Salvati index. Clinical outcomes were evaluated based on the Fulkerson patellofemoral joint evaluation score, Kujala score, and the presence of the apprehension sign. Radiological evaluation revealed significant postoperative improvements in the Q-angle, tilting angle, lateral shift ratio, congruence angle, Kujala score, and Fulkerson score (p < 0.001). Sixty-eight percent of all patients had a “good” or “excellent” Fulkerson score. The apprehension sign continued to be shown for six knees. Progression of osteoarthritic changes was observed in three knees, and one knee was symptomatic. The modified ET procedure provided satisfactory outcomes based on radiological and clinical evaluations. These results show the long-term effectiveness and safety of the modified ET procedure for recurrent patellar dislocation.
A bifunctional spin detector made of quantum anomalous Hall insulator
Authors: Shi Zhangsheng , Wu Jiansheng
Published: October 2016

The spin selection of the topological boundary states (TBS) which are protected by the chiral-like symmetry in quantum anomalous Hall insulator (QAHI) can be used to construct a bifunctional spin detector (SD). Such device made of QAHIs in parallel with opposite chirality can divide an incoming spin-polarized current into two outgoing currents. The agreement between numerical and analytical calculation proves that the SD device functions as both spin filter and spin separator well in reflecting the spin polarization of source material from the ratio of two currents. The monotonic relation of spin polarization and current ratio suggests that using such kind of device, the spin polarization can be obtained directly. We also find that such device has a broad working energy region attributed by the TBS within the bulk gap. Combining with the result that the current ratio is barely dependent on the coupling between candidate materials and device, it is reasonable to apply this technique with a stable measuring accuracy. Furthermore, the features such as having simple geometry, being manipulated without external magnetic field, and the prospect of working at room temperature make this proposed device seem promising in developing future low-power-consumption spintronic device.
White House science adviser talks space, climate change, and budgets
Authors: Kramer David
Published: October 2016

John Holdren recaps the Obama administration’s science policy achievements and disappointments.
Extragalactic survey aims to shed light on dark energy
Authors: Feder Toni
Published: October 2016

Robot-controlled optical fibers will help create 3D map of the cosmos.
The search for magnetic monopoles
Authors: Rajantie Arttu
Published: October 2016

The discovery of the mysterious hypothetical particles would provide a tantalizing glimpse of new laws of nature beyond the standard model.
Foodborne disease associated with travel
Authors: Bramwell Prue
Published: October 2016

The most important determinant of developing foodborne disease is travel destination. The risk is proportional to regions where there is a high level of unsanitary water supply, lack of food hygiene, lack of food safety regulation, fluctuating electricity supply and lack of education. In medium to high risk regions a travel kit, designed to prevent, minimise or treat the effects should be carried.
Near-term probabilistic forecast of significant wildfire events for the Western United States
Authors: Preisler Haiganoush K. , Riley Karin L. , Stonesifer Crystal S. , Calkin Dave E. , Jolly W. Matthew
Published: October 2016

Fire danger and potential for large fires in the United States (US) is currently indicated via several forecasted qualitative indices. However, landscape-level quantitative forecasts of the probability of a large fire are currently lacking. In this study, we present a framework for forecasting large fire occurrence – an extreme value event – and evaluating measures of uncertainties that do not rely on distributional assumptions. The statistical model presented here incorporates qualitative fire danger indices along with other location and seasonal specific explanatory variables to produce maps of forecasted probability of an ignition becoming a large fire, as well as numbers of large fires with measures of uncertainties. As an example, 6 years of fire occurrence data from the Western US were used to study the utility of two fire danger indices: the 7-Day Significant Fire Potential Outlook issued by Predictive Services in the US and the National Fire Danger Rating’s Energy Release Component. This exercise highlights the potential utility of the quantitative risk index as a real-time decision support tool that can enhance managers’ abilities to discriminate among planning areas in terms of the likelihood and range of expected significant fire events. The approach is applicable wherever there are archived historical data from both observed fires and fire danger indices.
Chapter 10. Stylistics and “He Wishes for the Cloths of Heaven” by W.B. Yeats
Authors: Short Mick
Published: October 2016

This chapter will provide a detailed stylistic analysis of ‘He Wishes for the
Cloths of Heaven’ by W. B. Yeats. The analysis will combine of a range of analytical
methods, most of which will be of the ‘good old steam stylistics’ variety, as
Ron Carter has called them, e.g. lexical, grammatical and phonetic structure in
relation to foregrounding analysis; but other methods of analysis will also be
used, e.g. cognitive metaphor and possible/textual worlds theory. At the core
of the analysis will be a discussion of how, and why, Yeats makes the cloths of
heaven in the poem seem intangible, mystical, even, and the role which deviant
semantic structure and also deviant parallel list constructions inside a particular
noun phrase play in the creation of this cognitive effect. Part of the reason for
the multifarious approach to analysis is to compare the usefulness of the various
kinds of methodology for the stylistic analysis of poetry. Attention will also be
paid to different possible interpretations/readings of the poem and what this
can tell us about the nature of effective interpretation.
Synthesis of c-axis oriented AlN thin films at room temperature
Authors: Tavsanoglu T.
Published: October 2016

In this study, aluminium nitride (AlN) thin films were synthesised by plasma-enhanced reactive DC magnetron sputtering on glass and Si (100) substrates and the effect of bias voltages on the structural, optical and morphological properties of the coatings has been studied. According to the grazing angle XRD studies, AlN in hexagonal (wurtzite) structure has been obtained for all the coatings. (002) plane c-axis oriented films have been achieved at 150 and 175 V bias voltages. AFM analyses demonstrated that with the increase in the bias voltages, a transformation from coarse to fine granular morphology has been occurred and smoother surfaces with a decrease in the surface roughness from 3.40 nm to about 1.90 nm were obtained. The results also demonstrated that the high transmittance values of AlN films were not affected by the change in the bias voltages and about 80% of transmittance obtained for all AlN films deposited in this study.
Molecular mechanisms underlying COPD-muscle dysfunction unveiled through a systems medicine approach
Authors: Marín de Mas Igor , Fanchon Eric , Papp Balázs , Kalko Susana , Roca Josep , Cascante Marta
Published: October 2016

Motivation

Skeletal muscle dysfunction is a systemic effect in one-third of patients with chronic obstructive pulmonary disease (COPD), characterized by high reactive-oxygen-species (ROS) production and abnormal endurance training-induced adaptive changes. However, the role of ROS in COPD remains unclear, not least because of the lack of appropriate tools to study multifactorial diseases.

Results

We describe a discrete model-driven method combining mechanistic and probabilistic approaches to decipher the role of ROS on the activity state of skeletal muscle regulatory network, assessed before and after an 8-week endurance training program in COPD patients and healthy subjects. In COPD, our computational analysis indicates abnormal training-induced regulatory responses leading to defective tissue remodeling and abnormal energy metabolism. Moreover, we identified tnf, insr, inha and myc as key regulators of abnormal training-induced adaptations in COPD. The tnf-insr pair was identified as a promising target for therapeutic interventions. Our work sheds new light on skeletal muscle dysfunction in COPD, opening new avenues for cost-effective therapies. It overcomes limitations of previous computational approaches showing high potential for the study of other multi-factorial diseases such as diabetes or cancer.

Supplementary information

Supplementary data are available at Bioinformatics online.
AUV-based acoustic observations of the distribution and patchiness of pelagic scattering layers during midnight sun†
Authors: Geoffroy Maxime , Cottier Finlo R , Berge Jørgen , Inall Mark E
Published: October 2016

An autonomous underwater vehicle (AUV) carrying 614 kHz RDI acoustic doppler current profilers (ADCPs) was deployed at four locations over the West Spitsbergen outer shelf in July 2010. The backscatter signal recorded by the ADCPs was extracted and analysed to investigate the vertical distribution and patchiness of pelagic organisms during midnight sun. At the northernmost locations (Norskebanken and Woodfjorden), fresher and colder water prevailed in the surface layer (0–20 m) and scatterers (interpreted as zooplankton and micronekton) were mainly distributed below the pycnocline. In contrast, more saline and warmer Atlantic Water dominated the surface layer at Kongsfjordbanken and Isfjordbanken and scatterers were concentrated in the top 20 m, above the pycnocline. Pelagic scatterers formed patchy aggregations at all locations, but patchiness generally increased with the density of organisms and decreased at depths >80 m. This study contributes to our understanding of the vertical distribution of pelagic organisms in the Arctic, and the spatial coverage of the AUV has extended early acoustic studies limited to Arctic fjords from 1D observations to a broader offshore coverage. Neither synchronized nor unsynchronized vertical migrations were detected, but autonomous vehicles with limited autonomy (<1 day) may not be as effective as long-term mooring deployments or long-range AUVs to study vertical migrations. Short-term AUV-based acoustic surveys of the pelagic communities are nonetheless highly complementary to Eulerian studies, in particular by providing spatial measurements of patchiness. Compared with ship-based or moored acoustic instruments, the 3D trajectory of AUVs also allows using acoustic instruments with higher frequencies and better size resolution, as well as the detection of organisms closer to the surface.
SENP1 regulates IFN-γ−STAT1 signaling through STAT3−SOCS3 negative feedback loop
Authors: Yu Tingting , Zuo Yong , Cai Rong , Huang Xian , Wu Shuai , Zhang Chenxi , Chin Y Eugene , Li Dongdong , Zhang Zhenning , Xia Nansong , Wang Qi , Shen Hao , Yao Xuebiao , Zhang Zhong-Yin , Xue Song , Shen Lei , Cheng Jinke
Published: October 2016

Interferon-γ (IFN-γ) triggers macrophage for inflammation response by activating the intracellular JAK−STAT1 signaling. Suppressor of cytokine signaling 1 (SOCS1) and protein tyrosine phosphatases can negatively modulate IFN-γ signaling. Here, we identify a novel negative feedback loop mediated by STAT3−SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B (PTP1B), in IFN-γ signaling. SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation. PTP1B in SENP1-deficient macrophages is highly SUMOylated, which reduces PTP1B-induced de-phosphorylation of STAT3. Activated STAT3 then suppresses STAT1 activation via SOCS3 induction in SENP1-deficient macrophages. Accordingly, SENP1-deficient macrophages show reduced ability to resist Listeria monocytogenes infection. These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in macrophage polarization.
Radiotherapy using IMRT boosts after hyperbaric oxygen therapy with chemotherapy for glioblastoma
Authors: Yahara Katsuya , Ohguri Takayuki , Udono Hiroki , Yamamoto Junkoh , Tomura Kyosuke , Onoda Toshihiro , Imada Hajime , Nishizawa Shigeru , Korogi Yukunori
Published: October 2016

The purpose of this study was to evaluate the feasibility and efficacy of radiotherapy (RT) using intensity-modulated radiotherapy (IMRT) boosts after hyperbaric oxygen (HBO) therapy with chemotherapy in patients with glioblastoma. Twenty-four patients with glioblastoma were treated with the combined therapy, which was RT using IMRT boosts after HBO with chemotherapy, and were retrospectively analyzed. The RT protocol was as follows: first, 3D conformal RT [40 Gy/20 fractions (fr)] was delivered to the gross tumor volume (GTV) and the surrounding edema, including an additional 1.5–2.0 cm. The IMRT boost doses were then continuously delivered to the GTV plus 5 mm (28 Gy/8 fr) and the surrounding edema (16 Gy/8 fr). Each IMRT boost session was performed immediately after HBO to achieve radiosensitization. The planned RT dose was completed in all patients, while HBO therapy was terminated in one patient (4%) due to Grade 2 aural pain. The toxicities were mild, no non-hematological toxicity of Grade 3–5 was observed. The 2-year overall survival (OS) and progression-free survival rates in all patients were 46.5% and 35.4%, respectively. The median OS time was 22.1 months. In conclusion, the combined therapy of RT using IMRT boosts after HBO with chemotherapy was a feasible and promising treatment modality for patients with glioblastoma. The results justify further evaluation to clarify the benefits of this therapy.
Optimal Time-Consistent Government Debt Maturity*
Authors: Debortoli Davide , Nunes Ricardo , Yared Pierre
Published: October 2016

This article develops a model of optimal government debt maturity in which the government cannot issue state-contingent bonds and cannot commit to fiscal policy. If the government can perfectly commit, it fully insulates the economy against government spending shocks by purchasing short-term assets and issuing long-term debt. These positions are quantitatively very large relative to GDP and do not need to be actively managed by the government. Our main result is that these conclusions are not robust to the introduction of lack of commitment. Under lack of commitment, large and tilted debt positions are very expensive to finance ex ante since they exacerbate the problem of lack of commitment ex post. In contrast, a flat maturity structure minimizes the cost of lack of commitment, though it also limits insurance and increases the volatility of fiscal policy distortions. We show that the optimal time-consistent maturity structure is nearly flat because reducing average borrowing costs is quantitatively more important for welfare than reducing fiscal policy volatility. Thus, under lack of commitment, the government actively manages its debt positions and can approximate optimal policy by confining its debt instruments to consols.
Comparison of efficacy of methyl prednisolone and triamcinolone in wrist ganglion using double dart technique and its application in an Indian population
Authors: Kumar Kuljit , Sharma Dhruv
Published: October 2016

Background:

Ganglion cysts are benign soft-tissue tumors most commonly encountered in the wrist. Treatment modalities described for ganglion cysts include conservative therapy, aspiration, steroid injection, and surgical excision. The purpose of the study was to compare the efficacy of methyl prednisolone and triamcinolone in wrist ganglia using the double dart technique in an Indian population.

Methods:

All wrist ganglia (dorsal and volar) were included in the study. Patients with diabetes mellitus, tuberculosis, or rheumatoid arthritis were not included in the study. The patients included in the study were randomly divided in two groups: in one group (n=24), aspiration and methyl prednisolone acetate, 1 mL (40 mg) was injected, and in the other group (n=24) aspiration and triamcinolone acetonide, 1 mL (40 mg) was injected using the double dart technique.

Results:

Of the 48 patients included in the study, 36 (75%) were women and 12 (25%) were men, showing a female preponderance. The mean age of the patients was 37.18±6.38 yr. There was no significant difference between the methyl prednisolone group and the triamcinolone group in terms of recurrence (Fisher’s exact test, P=1.6). There were no complications in either group, but the triamcinolone group reported more pain at the injection site.

Conclusions:

Injection with methyl prednisolone is as effective as injection with triamcinolone and avoids post-injection pain.
Extensor tendon splitting versus extensor tendon sparing approach for miniplate fixation of extraarticular proximal phalangeal fractures
Authors: Abubeih Hossam M.A. , Saleh Waleed Riad , Thabet Mostafa A. , Ibrahim Abdel-Khalek H.
Published: October 2016

Background:

Unstable phalangeal fractures constitute a challenge for surgeons with many options for operative treatment. Miniplate fixation of these fractures has the advantages of stability and neutralization of bending, rotational, and shear forces. To our knowledge, this is the first study to compare the functional results of an extensor tendon splitting approach with an extensor tendon sparing approach in extraarticular proximal phalangeal fractures fixed with a miniplate and screws.

Methods:

In a randomized prospective study we compared two groups of patients: group A, patients treated with an extensor tendon splitting approach (24 fractures in 21 patients with average age 31.9 yr) and group B, patients treated with an extensor tendon sparing approach (26 fractures in 19 patients with average age 30.8 yr). The final results were assessed with total active range of motion (TAM), grade of TAM, grip strength and Quick Disability of the Arm, Shoulder, and Hand (DASH) Score.

Results:

A TAM of 220 degrees or more was achieved in 79.2% (19/24) and 84.6% (22/26) of fractures in group A and B, respectively. There was a significant reduction in grip strength in group A compared to group B (45.9±8.4 kg vs. 51.7±7.3 kg; P<0.025). Other parameters showed slightly better results in group B compared with group A but the differences were statistically insignificant in regard to time to union (5.3+1 wk vs. 5.6+1.1 wk), TAM (226.8+18.4 degrees vs. 233.2+17.5 degrees), grading of TAM (excellent score 75% vs. 80.8%) and QuickDASH score (12±9.2 vs. 11.5±8.3).

Conclusions:

Meticulous surgical dissection, anatomical closure of layers, and early active mobilization are the keys to success in fixation of phalangeal fractures, regardless of the approach chosen.
Surgery for bone sarcomas of the lower extremity
Authors: Holt Ginger E. , Wilson Robert J.
Published: October 2016

Surgery for lower extremity bone sarcomas encompasses a wide array of surgical options beyond the classic treatment of amputation. Limb salvage surgery (LSS) in the form of arthroplasty, arthrodesis, or allograft reconstruction is now possible for most patients. Patient function, in addition to survival, has been increasingly emphasized as the 5-year survival is now typically over 60%. Recent research looking at the activity levels of patients after endoprosthetic reconstruction is reviewed. Advances in surgical navigation, expandable endoprostheses, and in treating infected allografts and endoprostheses are summarized. Long-term functional outcomes and neurologic plasticity in patients with rotationplasties are examined as well. Surgery for bone sarcomas remains a high-risk, high-reward endeavor that continues to improve through innovation.
Classification and management of Lisfranc joint injuries: current concepts
Authors: De-las-Heras Romero Jorge
Published: October 2016

The Lisfranc injury is a relatively rare traumatic pathology but has a significant impact on activities of daily living if not treated early and correctly. It has been shown that an adequate early intervention and an anatomical reduction with preservation of articular cartilage are the most important factors that influence the prognosis of these injuries. Management should, therefore, conform to this objective. We reviewed the literature in reference to the management of Lisfranc injuries and propose a new classification that better targets treatment and prognosis. In turn we suggest an appropriate treatment algorithm according to this new classification.
Non–Bachelor of Science in Nursing Registered Nurse to Bachelor of Science in Nursing Registered Nurse
Authors: McIntosh Constance E. , Thomas Cynthia M. , Siela Debra
Published: October 2016

With recommendations from national nursing associations and accrediting bodies to transition to an all baccalaureate prepared nurse workforce by 2020, it is important to understand the expertise that a baccalaureate degreed nurse brings to patient care. The purpose of this article is to establish the differences of a non–bachelor of science in nursing (BSN) registered nurse and a 4-year prepared nurse, as well as to identify the education and clinical trends in critical care that require a BSN-prepared nurse. The history of associate degree and diploma degree nurses is admirable and served a purpose serving up to and post World War II. In more recent years, particularly in critical care, as health care is becoming more complex, extension of technology, and pay-for-performance issues are tied to patient outcomes, it is essential the non-BSN registered nurses return to continue their education earning a BSN degree.
The α2C-adrenoceptor antagonist, ORM-10921, exerts antidepressant-like effects in the Flinders Sensitive Line rat
Authors: Uys Madeleine M. , Shahid Mohammed , Sallinen Jukka , Harvey Brian H.
Published: October 2016

Depression involves deficits in monoaminergic neurotransmission. Differential roles for α2A, B and C subtypes of the α2-adrenoceptor (AR) are evident, with selective α2C-AR antagonists purported to have antidepressant and procognitive properties. However, this has not been demonstrated in a genetic animal model of depression. The role of the α2C-AR in modulating two key depression-related behaviours in the Flinders Sensitive Line (FSL) rat was studied using a dose–response analysis following subcutaneous administration with the selective α2C-AR antagonist ORM-10921 (0.03; 0.3 mg/kg), the nonselective α2-AR antagonist idazoxan (3 mg/kg), or vehicle once daily for 14 days. Behaviour in the novel object recognition test, forced swim test (FST) and locomotor activity test was assessed. To ratify the validity of the FSL model, the reference tricyclic antidepressant imipramine (15 mg/kg, intraperitoneally) was used as a comparator drug in the FST. FSL rats demonstrated significantly increased immobility and recognition memory deficits versus Flinders Resistant Line controls, with imipramine significantly reversing said immobility. Similarly, ORM-10921 at both doses but not idazoxan significantly reversed immobility in the FST as well as attenuated cognitive deficits in FSL animals. We conclude that selective α2C-AR antagonism has potential as a novel therapeutic strategy in the treatment of depression and cognitive dysfunction.
TOMOGRAPHIC RELATIONSHIPS BETWEEN RETINAL NEOVASCULARIZATION AND THE POSTERIOR VITREOUS IN PROLIFERATIVE DIABETIC RETINOPATHY
Authors: Vaz-Pereira Sara , Dansingani Kunal K. , Chen Kevin C. , Cooney Michael J. , Klancnik James M. , Engelbert Michael
Published: October 2016

Purpose:

To describe anatomical relationships of retinal neovascular complexes (NVCs) and the posterior vitreous in proliferative diabetic retinopathy using spectral domain optical coherence tomography.

Methods:

Cross-sectional study. Neovascular complexes were imaged using spectral domain optical coherence tomography in 51 eyes of 37 patients. The relationship of NVCs to the posterior vitreous cortex and posterior vitreous spaces, such as the premacular bursa, prevascular vitreous fissures, and perimacular cisterns, was analyzed.

Results:

In the 77 NVCs evaluated, 61 (79%) had grown along the outer surface of the posterior hyaloid face, and vitreoschisis was present in 37 (48%). The “wolf's jaw” configuration was present in 9% and resulted from NVC arising from the arcades and proliferating along the posterior hyaloid face. By contrast, NVCs that invaded the bursa originated from smaller venous tributaries more distant from the arcades. The premacular bursa and prevascular vitreous fissure/perimacular cistern were invaded infrequently, respectively, in 15% and 38% (P = 0.137).

Conclusion:

Tomographic analysis of diabetic NVCs showed that most NVCs arise and grow along the posterior hyaloid face and that vitreoschisis is more prevalent than what has been found in ultrasound studies. The wolf's jaw configuration does not seem to result from the invasion of the bursa, as previously suggested.
Higher-Order Aberrations After Cyclopentolate, Tropicamide, and Artificial Tear Drops Application in Normal Eyes
Authors: Amirshekarizadeh Negin , Hashemi Hassan , Jafarzadehpur Ebrahim , Mirzajani Ali , Yekta Abbasali , Khabazkhoob Mehdi
Published: October 2016

Purpose:

To determine the effect of cyclopentolate, tropicamide, and artificial tear drops on higher-order aberrations (HOAs) in normal eyes with OPD-Scan III (Nidek Inc., Tokyo, Japan).

Methods:

In this study, 189 eyes of individuals aged 20 to 35 years were selected as samples. Inclusion criteria were a corrected visual acuity of 20/20 or better, a minimum size of about 5 mm for the pupil in the dark, hyperopia and myopia less than 5 D, and astigmatism less than 2 D. Moreover, participants with pathological eye problems, a history of intraocular surgery, and ocular diseases affecting the accommodation, pupil size, and corneal surface were excluded. Higher-order aberrations of the participants were assessed by the OPD-Scan III before and after cyclopentolate (Colircuss), tropicamide (Mydrax 0.5%), and artificial tears (Tearlose) drop instillation.

Results:

After instilling cyclopentolate drops, the mean of the total root mean square (RMS) increased from 4.580 to 6.335 D, total spherical aberration increased from 0.155 to 0.381 D, and total coma increased from 0.195 to 0.369 D; the increases were significant for total RMS and total spherical aberration, but a significant relationship was not seen with total coma. After tropicamide, the mean aberrations of total RMS increased from 4.301 to 4.568 D, total spherical aberration increased from 0.146 to 0.160 D, and total coma increased from 0.213 to 0.230 D; the increase was only significant for total coma. On the other hand, after artificial tears, the average of all aberrations decreased in a nonsignificant manner.

Conclusion:

Most changes of mean aberrations were related to cyclopentolate drops. Tropicamide and artificial tears had the second and third rank according to their effect on mean errors. As a result, it seems that ocular accommodation is the most important impact on HOA than pupil size. However, the pupil size is the second factor for HOAs.
High Levels of Decisional Conflict and Decision Regret When Making Decisions About Biologics
Authors: Lipstein Ellen A. , Lovell Daniel J. , Denson Lee A. , Kim Sandra C. , Spencer Charles , Ittenbach Richard F. , Britto Maria T.
Published: October 2016

Objectives:

The aim of the study was to understand the association between parents’ perceptions of the decision process and the decision outcomes in decisions about the use of biologics in pediatric chronic conditions.

Methods:

We mailed surveys to parents of children with inflammatory bowel disease or juvenile idiopathic arthritis who had started treatment with biologics in the prior 2 years and were treated at either of 2 children's hospitals. The survey included measures of the decision process, including decision control and physician engagement, and decision outcomes, including conflict and regret. We used means and frequencies to assess the response distributions. General linear models were used to test the associations between decision process and decision outcomes.

Results:

We had 201 respondents (response rate 54.9%). Approximately 47.0% reported using shared decision making. Each physician engagement behavior was experienced by the majority of parents, with the highest percentage reporting that their child's physician used language they understood and listened to them. Approximately 48.5% of parents had decisional conflict scores of 25 or greater, indicating high levels of conflict. Approximately 28.2% had no regret, 31.8% had mild regret, and the remaining 40.0% had moderate to severe regret. Shared decision making was not associated with improved decisional conflict, but physician engagement behaviors were associated with both decisional conflict and regret.

Conclusions:

Improving decision outcomes will require more than just focusing on who parents perceive as controlling the final decision. Developing interventions that facilitate specific physician engagement behaviors may decrease parents’ distress around decision making and improve decision outcomes.
Ultrasound‐Guided Liver Biopsy With Gelatin Sponge Pledget Tract Embolization in Infants Weighing Less Than 10 kg
Authors: Lungren Matthew P. , Lindquester Will S. , Seidel Frank Glen , Kothary Nishita , Monroe Eric J. , Shivaram Giri , Gill Anne E. , Hawkins Matthew C.
Published: October 2016

Objectives:

The aim of the study was to describe and assess the technical success and safety of ultrasound‐guided liver biopsy with gelatin sponge pledget tract embolization technique in infants <10 kg across 3 tertiary pediatric hospitals.

Materials and Methods:

There were 67 pediatric patients weighing <10 kg (36 boys; 31 girls; average age 202 days; average weight 6 kg, range 1.5–9.9 kg) referred for liver biopsy performed with ultrasound guidance and gelatin sponge pledget tract embolization during a 2‐year period. Patient history, procedural records, and clinical follow‐up documents were retrospectively reviewed.

Results:

A total of 67 procedures were included. There was 100% technical success rate and all samples obtained provided adequate tissue for histological assessment. Average number of 18 G biopsy passes was 3 (range 1–6). There were no procedure‐related deaths. There was 1 complication (1%) in a 5‐kg infant who was readmitted 36 hours after biopsy with a fever and fully recovered after antibiotics were administered. Biliary atresia was the most common underlying diagnosis (20%), whereas others included acute rejection (16%) and biliary obstruction (7%).

Conclusions:

Ultrasound‐guided percutaneous liver biopsy with gelatin sponge pledget tract embolization technique in children weighing <10 kg is safe, effective, and use of this technique may lead to a reduction in rates of adverse events reported in other pediatric series.
Predictors of physical independence at discharge after stroke rehabilitation in a Dutch population
Authors: Ten Brink Antonia F. , Hajos Tibor R.S. , van Bennekom Coen , Nachtegaal Janneke , Meulenbelt Henk E.J. , Fleuren Judith F.M. , Kouwenhoven Mirjam , Luijkx Marscha M. , Wijffels Markus P. , Post Marcel W.M.
Published: October 2016

The aim of this study was to identify predictors, available at admission, of physical independence at discharge from inpatient rehabilitation. Secondary aims were to identify predictors of functional gain and length of stay (LOS). We included 1310 adult stroke patients who were admitted for inpatient rehabilitation in five Dutch rehabilitation centres. Data on the Utrecht Scale for Evaluation of Clinical Rehabilitation at admission and discharge (physical and cognitive independence, mood, pain and fatigue), age, sex and in a subsample stroke characteristics as well were collected. A prediction model was created using random coefficient analysis. None of the stroke characteristics were independently associated with physical independence or functional gain at discharge, or LOS. Higher physical and cognitive independence scores and severe pain at admission were predictors of higher physical independence scores at discharge. Furthermore, lower physical independence scores, higher cognitive independence scores, less pain at admission and younger age predicted more functional gain. Finally, lower physical and cognitive independence scores at admission and younger age predicted longer LOS. Physical independence at admission was the most robust predictor for rehabilitation outcome in a Dutch rehabilitation setting. To a lesser extent, age, cognitive independence and pain predicted rehabilitation outcome after stroke. Treatment of cognition and pain should be taken into account during rehabilitation. Further work needs to be carried out to establish whether focusing on these factors improves outcome after rehabilitation.
Bottle Tongue Entrapment
Authors: Long Michael T. , Murray Matthew P.
Published: October 2016

Tongue entrapments within bottles are very rare childhood mishaps. The most immediate hazard in a tongue entrapment is airway obstruction. Tongue entrapment is an airway emergency; contingency planning to maintain airway patency, oxygenation, and ventilation is critical. Here, we report the case of a 5-year-old girl presenting to a pediatric emergency department with an increasingly popular novelty soda bottle, featuring a unique and dangerous design, entrapped on her tongue. Operative removal was anticipated. Although initially stable, she became agitated and developed retching while awaiting transfer to the operating room. Symptoms were managed medically after careful consideration of the risks and benefits of drug adverse effects while airway contingencies were planned. Fortunately, airway interventions were not necessary in the emergency department. The child was transferred to and intubated in the operating room where the bottle was removed uneventfully. This case demonstrates our approach to an evolving difficult airway in our pediatric emergency department. We review the available literature on similar presentations.
Acute Liver Failure
Authors: Núñez-Ramos Raquel , Montoro Soledad , Bellusci Marcello , del Fresno-Valencia María Rosa , Germán-Díaz Marta , Urruzuno Pedro , Medina Enrique , Manzanares Javier
Published: October 2016

Purpose

The aims of this study were to analyze the characteristics of patients with acute liver failure (ALF) in our center and evaluate the prognostic value of the Pediatric End-Stage Liver Disease (PELD) score calculated at admission.

Methods

A retrospective analysis of patients with ALF younger than 15 years between 2005 and 2013 was performed. Information collected included age, sex, etiology of ALF, laboratory tests, PELD score, stage of encephalopathy, and need for liver support devices such as MARS and/or liver transplant (LT) and survival. A poor prognosis was defined as the need for LT or death.

Results

Twenty patients (10 male patients, 50%) with a median age of 2.6 years (3 days-14.5 y old) were included. Acute liver failure was of indeterminate cause in 5 cases (25%). Within the recognized causes, the most frequent were viral hepatitis (herpes simplex virus, adenovirus, influenza B, Epstein-Barr virus), autoimmune hepatitis, and metabolopathies. Sixty percent presented with encephalopathy at diagnosis. Four patients were aided by a MARS liver support device. Six patients received a total of 7 transplants, all from deceased donors. The rate of spontaneous recovery was 45%. Currently 13 patients (65%) are living, 4 of them with an LT. Six patients died because of ALF. The mean PELD score of patients with spontaneous recovery was 15.31 (5.3–27.6) compared with a mean of 29.5 (17.2–39.4) in LT patients and 31.55 (15.8–52.4) for nonsurvivors (P = 0.013).

Conclusions

High PELD scores at diagnosis were accurate predictors of a poor prognosis in our patients with ALF. This model may help in the clinical management of this entity, although prospective validation is needed.
Etiology and Outcome of Severe Apparent Life-Threatening Events in Infants
Authors: Radovanovic Tanja , Spasojevic Slobodan , Stojanovic Vesna , Doronjski Aleksandra
Published: October 2016

Introduction

An apparent life-threatening event (ALTE) is defined as “an episode that is frightening to the observer and is characterized by some combination of apnea, color change, marked change of muscle tone, choking, or gagging.”

Objective

The aims of this study were to determine etiology and outcome of severe ALTE (requiring resuscitation measures) and to review diagnostic approaches in infants hospitalized after such an episode of ALTE.

Methods

Retrospective analysis included patients hospitalized at the Intensive Care Unit, Institute of Child and Youth Healthcare of Vojvodina, after an episode of severe ALTE over a 4-year period.

Results

The study included 23 infants, 18 male (78.3%), and 5 female (21.7%). The average age at presentation was 78 days (1 day to 11 months). In 8 infants (34.7%), ALTE resulted in death. The most frequent conditions after diagnostic evaluation were lower respiratory tract infections (39.1%), intracranial and extracranial hemorrhages (13.0%), and central nervous system infections (8.6%). The cause remained unknown in 8.7% of cases. Initial investigations included complete blood cell count, C-reactive protein or procalcitonin, blood gasses, lactate, electrolytes, glucose, blood culture, urinalysis, and chest x-ray.

Conclusions

Apparent life-threatening event represents a diverse disorder. Lower respiratory tract infections and neurological disorders were the most common established etiology. Prematurity and congenital heart diseases stood out as important risk factors. Diagnostic evaluation varied according to suspected cause and trigger factors.
The Beef Jerky Blues
Authors: Theobald Jillian L. , Spoelhof Rachel , Pallasch Erin M. , Mycyk Mark B.
Published: October 2016

Methemoglobinemia can result from ingestion of nitrite- or nitrate-containing foods. Here, we report a case where an adolescent girl and her father developed clinically significant methemoglobinemia after ingestion of “homemade” beef jerky prepared with sodium nitrate salt purchased at a local grocery store. Both had palpitations, dyspnea, and visible mucosal cyanosis. The daughter had a methemoglobin level of 44.2% and the father's methemoglobin level was 34.2%. Prompt recognition of methemoglobinemia is important for initiating antidotal therapy with methylene blue.
Mito-nuclear Incompatibilities and Mitochondrial Replacement Therapy
Authors: Eyre-Walker Adam
Published: October 2016

Mitochondrial replacement therapy (MRT) is a human reproductive technology by which the mitochondria of a recipient’s eggs are effectively replaced by those of a donor, potentially eliminating harmful mitochondrial mutations carried by the recipient. However, concerns have been raised that MRT may lead to problems due to incompatibilities between the nuclear genome of the recipient and mitochondrial genome of the donor. Whether this is likely to be a problem is investigated using 226 estimates, taken from the literature, of the effect of replacing the “native” by a “foreign” mitochondrial DNA (mtDNA) from the same species in a variety of animals. In approximately half of the cases (45%), strains with the foreign mtDNA have higher fitness than those with the native mtDNA, and on average the native strains are only 3% fitter. Based on these results it is argued that incompatibilities between the mitochondrial and nuclear genomes are not likely to be a problem for MRT.
Comparative analysis of variation and selection in the HCV genome
Authors: Patiño-Galindo Juan Ángel , González-Candelas Fernando
Published: October 2016

Genotype 1 of the hepatitis C virus (HCV) is the most prevalent of the variants of this virus. Its two main subtypes, HCV-1a and HCV-1b, are associated to differences in epidemic features and risk groups, despite sharing similar features in most biological properties. We have analyzed the impact of positive selection on the evolution of these variants using complete genome coding regions, and compared the levels of genetic variability and the distribution of positively selected sites. We have also compared the distributions of positively selected and conserved sites considering different factors such as RNA secondary structure, the presence of different epitopes (antibody, CD4 and CD8), and secondary protein structure. Less than 10% of the genome was found to be under positive selection, and purifying selection was the main evolutionary force in both subtypes. We found differences in the number of positively selected sites between subtypes in several genes (Core, HVR2 inE2, P7, helicase inNS3andNS4a).Heterozygosity values in positively selected sites and the rate of non-synonymous substitutions were significantly higher in subtype HCV-1b. Logistic regression analyses revealed that similar selective forces act at the genome level in both subtypes: RNA secondary structure and CD4 T-cell epitopes are associated with conservation, while CD8 T-cell epitopes are associated with positive selection in both subtypes. These results indicate that similar selective constraints are acting along HCV-1a and HCV-1b genomes, despite some differences in the distribution of positively selected sites at independent genes.