bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Oral Anticoagulant Choice for Acute Stroke Patients with Nonvalvular Atrial Fibrillation in Japan: The SAMURAI-NVAF Study
Authors: Toyoda Kazunori , Arihiro Shoji , Todo Kenichi , Yamagami Hiroshi , Kimura Kazumi , Furui Eisuke , Terasaki Tadashi , Shiokawa Yoshiaki , Kamiyama Kenji , Takizawa Shunya , Okuda Satoshi , Okada Yasushi , Kameda Tomoaki , Nagakane Yoshinari , Hasegawa Yasuhiro , Mochizuki Hiroshi , Ito Yasuhiro , Nakashima Takahiro , Takamatsu Kazuhiro , Nishiyama Kazutoshi , Kario Kazuomi , Sato Shoichiro , Koga Masatoshi ,   for the SAMURAI Study Investigators
Published: January 2015

Background

Large clinical trials are lack of data on non-vitamin K antagonist oral anticoagulants for acute stroke patients.

Aim

To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry (ClinicalTrials.gov NCT01581502).

Method

The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23-day stay) was assessed.

Results

Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10-month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS2, CHA2DS2-VASc, and HAS-BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four-days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20-day or shorter hospitalization (OR 2·46, 95% CI 1·87–3·24).

Conclusions

Warfarin use at acute hospital discharge was still common in the initial years after approval of nonvitamin K antagonist oral anticoagulants, although nonvitamin K antagonist oral anticoagulant users increased gradually. The index stroke was milder and ischemia-risk indices were lower in nonvitamin K antagonist oral anticoagulant users than in warfarin users. Early initiation of nonvitamin K antagonist oral anticoagulants seemed safe.
Treatment of patients with multiple myeloma who are eligible for stem cell transplantation: position statement of the Myeloma Foundation of Australia Medical and Scientific Advisory Group
Authors: Quach H. , Joshua D. , Ho J. , Szer J. , Spencer A. , Harrison S. J. , Mollee P. , Roberts A. W. , Horvath N. , Talulikar D. , To B. , Zannettino A. , Brown R. , Catley L. , Augustson B. , Jaksic W. , Gibson J. , Prince H. M.
Published: January 2015

The survival of patients with multiple myeloma (MM) has improved substantially since the introduction in the late 1980s of high‐dose chemotherapy (HDT) supported by autologous stem cell transplantation (ASCT). Further improvements have been observed following the availability of immunomodulatory drugs (IMiD) such as thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib. Here, we summarise the recommendations of the Medical Scientific Advisory Group to the Myeloma Foundation of Australia for patients considered suitable for HDT + ASCT as part of initial therapy. These recommendations incorporate the various phases of treatment: induction, HDT conditioning and maintenance therapy.
Immune mechanisms linked to depression via oxidative stress and neuroprogression
Authors: Bakunina Nataliia , Pariante Carmine M. , Zunszain Patricia A.
Published: January 2015

Emerging evidence suggests a significant role for inflammation and oxidative stress as main contributors to the neuroprogression that is observed in major depressive disorder (MDD), where patients show increased inflammatory and oxidative stress biomarkers. The process of neuroprogression includes stage‐related neurodegeneration, cell death, reduced neurogenesis, reduced neuronal plasticity and increased autoimmune responses. Oxidative stress is a consequence of the biological imbalance between reactive oxygen species (ROS) and antioxidants, leading to the alteration of biomolecules and the loss of control of the intracellular redox‐related signalling pathways. ROS serve as crucial secondary messengers in signal transduction and significantly affect inflammatory pathways by activating nuclear factor‐κB and mitogen‐activated protein kinase family stress kinases. When present in excess, ROS inflict damage, affecting cellular constituents with the formation of pro‐inflammatory molecules, such as malondialdehyde, 4‐hydroxynonenal, neoepitopes and damage‐associated molecular patterns promoting immune response, and ultimately leading to cell death. The failure of cells to adapt to the changes in redox homeostasis and the subsequent cell death, together with the damage caused by inflammatory mediators, have been considered as major causes of neuroprogression and hence MDD. Both an activated immune–inflammatory system and increased oxidative stress act synergistically, complicating our understanding of the pathogenesis of depression. The cascade of antioxidative and inflammatory events is orchestrated by several transcription factors, with nuclear factor (erythroid‐derived 2)‐like 2 and nuclear factor‐κB having particular relevance to MDD. This review focuses on potential molecular mechanisms through which impaired redox homeostasis and neuroinflammation can affect the neuronal environment and contribute to depression.
Six‐month outcomes in dental patients identified with hyperglycaemia: a randomized clinical trial
Authors: Lalla Evanthia , Cheng Bin , Kunzel Carol , Burkett Sandra , Ferraro Andrew , Lamster Ira B.
Published: January 2015

Aim

To assess an approach to improving behavioural and glycaemic outcomes in dental patients who present with diabetes risk factors and previously unrecognized hyperglycaemia.

Methods

We randomized 101 individuals identified with potential diabetes or pre‐diabetes into two interventions. In the basic/control intervention, participants were informed about their diabetes risk factors and blood test result, and advised to see a physician. In the enhanced/test intervention, patients received a detailed explanation of findings and their implications, a written report for the physician, and were contacted at 2 and 4 months to inquire whether medical follow‐up had occurred. At a 6‐month re‐evaluation, outcome measures included visit to physician, positive lifestyle changes and reduction in HbA1c.

Results

Seventy‐three subjects returned for the 6‐month visit. The two intervention groups did not significantly differ in any of the outcome variables. Eighty‐four percent of subjects reported having visited a physician post‐randomization, and 49% reported at least one positive lifestyle change as a result of our intervention. In subjects identified with potential diabetes (baseline HbA1c ≥ 6.5%), HbA1c was reduced 1.46 ± 0.28% compared to baseline (p < 0.01).

Conclusion

Diabetes risk assessment and education by dental professionals of affected individuals unaware of their status may contribute to improved patient outcomes.
Systemically administered neuregulin‐1β1 rescues nigral dopaminergic neurons via the ErbB4 receptor tyrosine kinase in MPTP mouse models of Parkinson's disease
Authors: Depboylu Candan , Rösler Thomas W. , de Andrade Anderson , Oertel Wolfgang H. , Höglinger Günter U.
Published: January 2015

Previously, we demonstrated that systemically injected extracellular domain of neuregulin‐1β1 (Nrg1β1), a nerve growth and differentiation factor, passes the blood‐brain barrier and rescues dopaminergic neurons of substantia nigra in the 6‐hydroxydopamine‐mouse model of Parkinson's disease (PD). Here, we studied the effects of peripherally administered Nrg1β1 in another toxin‐based mouse model of PD. For this purpose, (i) nigrostriatal pathway injury was induced by treatment of adult wild‐type mice with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in acute and subchronic paradigms; and (ii) Nrg1β1 or saline (control) were administered 1 h before each MPTP injection. We found that Nrg1β1 significantly reduced the loss of nigral dopaminergic neurons in both intoxication paradigms (7 days post‐injection). However, Nrg1β1 did not reverse MPTP‐induced decrease in dopamine levels and dopaminergic fibers in the striatum. We also show that MPTP conversion to its toxic metabolite 1‐methyl‐4‐phenylpyridinium as well as levels of dopamine transporter, mediating intracellular uptake of 1‐methyl‐4‐phenylpyridinium, are unaffected by Nrg1β1. Finally, neuroprotective properties of Nrg1β1 on nigral dopaminergic neurons are specifically mediated by ErbB4 as revealed through the study of ErbB4 knockout mice. In conclusion, systemically administered Nrg1β1 protects midbrain dopaminergic neurons against this PD‐related toxic insult. Thus, Nrg1β1 may have a benefit in the treatment of PD patients.

image

Previously, we demonstrated that systemically administered neuregulin‐1β1 (Nrg1β1) passes the blood‐brain barrier, phosphorylates ErbB4 receptors and elevates dopamine (DA) levels in the nigrostriatal system of healthy mice. Nrg1β1 protects nigral DAergic neurons in the 6‐hydroxydopamine (6‐OHDA) mouse model of Parkinson's disease (PD). Here, we show that Nrg1β1 rescues nigral DAergic neurons also against 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced cell death. ErbB4 expression is essential for the neuroprotective effect of Nrg1β1 on midbrain DAergic neurons. Nrg1β1 might be beneficial in PD treatment.
Rhythmic control of mRNA stability modulates circadian amplitude of mouse Period3 mRNA
Authors: Kim Sung‐Hoon , Lee Kyung‐Ha , Kim Do‐Yeon , Kwak Eunyee , Kim Seunghwan , Kim Kyong‐Tai
Published: January 2015

The daily oscillations observed in most living organisms are endogenously generated with a period of 24 h, and the underlying structure of periodic oscillation is an autoregulatory transcription‐translation feedback loop. The mechanisms of untranslated region (UTR)‐mediated post‐transcriptional regulation (e.g., mRNA degradation and internal ribosomal entry site (IRES)‐mediated translation) have been suggested to fine‐tune the expression of clock genes. Mouse Period3 (mPer3) is one of the paralogs of Period gene and its function is important in peripheral clocks and sleep physiology. mPer3 mRNA displays a circadian oscillation as well as a circadian phase‐dependent stability, while the stability regulators still remain unknown. In this study, we identify three proteins – heterogeneous nuclear ribonucleoprotein (hnRNP) K, polypyrimidine tract‐binding protein (PTB), and hnRNP D – that bind to mPer3 mRNA 3′‐UTR. We show that hnRNP K is a stabilizer that increases the amplitude of circadian mPer3 mRNA oscillation and hnRNP D is a destabilizer that decreases it, while PTB exhibits no effect on mPer3 mRNA expression. Our experiments describe their cytoplasmic roles for the mRNA stability regulation and the circadian amplitude formation. Moreover, our mathematical model suggests a mechanism through which post‐transcriptional mRNA stability modulation provides not only the flexibility of oscillation amplitude, but also the robustness of the period and the phase for circadian mPer3 expression.

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Mouse Period3 (mPer3) is one of well‐known clock genes. We identified three 3′‐UTR‐binding proteins that modulate the mRNA stability, and they influenced to the amplitude of circadian mPer3 mRNA oscillation. Our mathematical model not only showed the relationship between mRNA stability and its oscillation profile but provided the molecular mechanism for the robustness of the period and the phase in circadian oscillation. hnK, heterogeneous nuclear ribonucleoprotein (hnRNP) K; hnD, hnRNP D; PTB, polypyrimidine tract‐binding protein.
Valproic acid induces neuronal cell death through a novel calpain‐dependent necroptosis pathway
Authors: Bollino Dominique , Balan Irina , Aurelian Laure
Published: January 2015

A growing body of evidence indicates that valproic acid (VPA), a histone deacetylase inhibitor used to treat epilepsy and mood disorders, has histone deacetylase‐related and ‐unrelated neurotoxic activity, the mechanism of which is still poorly understood. We report that VPA induces neuronal cell death through an atypical calpain‐dependent necroptosis pathway that initiates with downstream activation of c‐Jun N‐terminal kinase 1 (JNK1) and increased expression of receptor‐interacting protein 1 (RIP‐1) and is accompanied by cleavage and mitochondrial release/nuclear translocation of apoptosis‐inducing factor, mitochondrial release of Smac/DIABLO, and inhibition of the anti‐apoptotic protein X‐linked inhibitor of apoptosis (XIAP). Coinciding with apoptosis‐inducing factor nuclear translocation, VPA induces phosphorylation of the necroptosis‐associated histone H2A family member H2AX, which is known to contribute to lethal DNA degradation. These signals are inhibited in neuronal cells that express constitutively activated MEK/ERK and/or PI3‐K/Akt survival pathways, allowing them to resist VPA‐induced cell death. The data indicate that VPA has neurotoxic activity and identify a novel calpain‐dependent necroptosis pathway that includes JNK1 activation and RIP‐1 expression.

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A growing body of evidence indicates that valproic acid (VPA) has neurotoxic activity, the mechanism of which is still poorly understood. We report, for the first time, that VPA activates a previously unrecognized calpain‐dependent necroptosis cascade that initiates with JNK1 activation and involves AIF cleavage/nuclear translocation and H2AX phosphorylation as well as an altered Smac/DIABLO to XIAP balance.
The clinical success of tooth‐ and implant‐supported zirconia‐based fixed dental prostheses. A systematic review
Authors: Le M. , Papia E. , Larsson C.
Published: January 2015

The aim was to make an inventory of the current literature on the clinical performance of tooth‐ or implant‐supported zirconia‐based FDPs and analyse and discuss any complications. Electronic databases, PubMed.gov, Cochrane Library and Science Direct, were searched for original studies reporting on the clinical performance of tooth‐ or implant‐supported zirconia‐based FDPs. The electronic search was complemented by manual searches of the bibliographies of all retrieved full‐text articles and reviews, as well as a hand search of the following journals: International Journal of Prosthodontics, Journal of Oral Rehabilitation, International Journal of Oral & Maxillofacial Implants and Clinical Oral Implants Research. The search yielded 4253 titles. Sixty‐eight potentially relevant full‐text articles were retrieved. After applying pre‐established criteria, 27 studies were included. Twenty‐three studies reported on tooth‐supported and 4 on implant‐supported FDPs. Five of the studies were randomised, comparing Y‐TZP‐based restorations with metal–ceramic or other all‐ceramic restorations. Most tooth‐supported FDPs were FDPs of 3–5 units, whereas most implant‐supported FDPs were full arch. The majority of the studies reported on 3‐ to 5‐year follow‐up. Life table analysis revealed cumulative 5‐year survival rates of 93·5% for tooth‐supported and 100% for implant‐supported FDPs. For tooth‐supported FDPs, the most common reasons for failure were veneering material fractures, framework fractures and caries. Cumulative 5‐year complication rates were 27·6% and 30·5% for tooth‐ and implant‐supported FDPs, respectively. The most common complications were veneering material fractures for tooth‐ as well as implant‐supported FDPs. Loss of retention occurred more frequently in FDPs luted with zinc phosphate or glass–ionomer cement compared to those luted with resin cements. The results suggest that the 5‐year survival rate is excellent for implant‐supported zirconia‐based FDPs, despite the incidence of complications, and acceptable for tooth‐supported zirconia‐based FDPs. These results are, however, based on a relatively small number of studies, especially for the implant‐supported FDPs. The vast majority of the studies are not controlled clinical trials and have limited follow‐up. Thus, interpretation of the results should be made with caution. Well‐designed studies with large patient groups and long follow‐up times are needed before general recommendations for the use of zirconia‐based restorations can be provided.
In vivo adverse effects of alpha‐tocopherol on the semen quality of male bucks
Authors: Majid A. , Qureshi M. S. , Khan R. U.
Published: January 2015

Oxidative stress has detrimental effects on semen quality during spermatogenesis and semen processing for artificial insemination. This work was conducted to study the effect of different levels of vitamin E on the semen traits, oxidative status and trace minerals in Beetal bucks. Thirty‐six bucks of similar body weight and age (1 year) were randomly divided into four groups. One group was kept as control with no supplementation (group 1), and the others were supplemented with 200 (group 2), 400 (group 3) and 800 IU (group 4) vitamin E/animal/day for 2 months. At the end of the experiment, semen samples were collected and evaluated. Seminal plasma was separated to study the concentration of superoxide dismutase (SOD), glutathione peroxidase (GPx), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and trace minerals (Zn, Cu, Mn and Fe). Group 3 showed significantly higher (p < 0.05) semen volume and per cent motility and lower dead sperm percentage compared to control group. Superoxide dismutase, GPx, Zn, Cu and Mn were higher in the same group. The level of AST decreased in group 3 without any change on the concentration of ALT. It is suggested that vitamin E at the rate of 400 IU/buck/day supported higher semen volume, per cent motility, per cent live spermatozoa, antioxidants (SOD, GPx) and trace mineral levels (Zn, Cu, Mn) in the seminal plasma. The increased supplementation from 0 to 400 showed a general increasing trend in improving semen quality. However, the dose of 800 IU/kg had no useful effect in further improving the semen quality.
Nutrient and mineral composition during shoot growth in seven species ofPhyllostachysandPseudosasabamboo consumed by giant panda
Authors: Christian A. L. , Knott K. K. , Vance C. K. , Falcone J. F. , Bauer L. L. , Fahey G. C. , Willard S. , Kouba A. J.
Published: January 2015

During the annual period of bamboo shoot growth in spring, free‐ranging giant pandas feed almost exclusively on the shoots while ignoring the leaves and full‐ height culm. Little is known about the nutritional changes that occur during bamboo shoot growth, if nutritional changes differ among species, or how these changes might influence forage selection. Our objective was to examine the nutrient and mineral composition during three phases of shoot growth (<60, 90–150 and >180 cm) for seven species of bamboo (Phyllostachys(P.)aurea,P. aureosulcata,P. bissetii,P. glauca,P. nuda,P. rubromarginata,Pseudosasa japonica) fed to captive giant pandas at the Memphis Zoo. Total dietary fiber content of bamboo shoots increased (p < 0.0001) from an overall species average of 61% dry matter (DM) at < 60 cm to 75% DM at shoot heights > 180 cm, while crude protein, fat and ash exhibited significant declines (p < 0.05).Phyllostachys nudahad the overall greatest (p = 0.007) crude protein (21% DM) and fat (4% DM) content, and lowest overall total fibre (61% DM) content compared to the other species examined. In contrast,Pseudosasa japonicahad the overall lowest crude protein and fat, and relatively higher fibre content (9%, 3% and 74% respectively). Concentrations of Zn and Fe were highest in shoots <60 cm (10–50 μg/g DM) and decreased (p < 0.05) during growth in all species examined. Concentrations of Ca, Cu, Mn, Na and K varied among species and were largely unaffected by growth stage. Due to their higher concentrations of nutrients and lower fibre content in comparison to culm and leaf, bamboo shoots should be a major component of captive giant panda diets when available.
Efficacy and safety of telbivudine treatment: an open‐label, prospective study in pregnant women for the prevention of perinatal transmission of hepatitis B virus infection
Authors: Han G.‐R. , Jiang H.‐X. , Yue X. , Ding Y. , Wang C.‐M. , Wang G.‐J. , Yang Y.‐F.
Published: January 2015

We evaluated the efficacy and safety of telbivudine (LdT, 600 mg/day) vs control patients (no treatment) in decreasing vertical transmission of HBV, in HBeAg‐positive mothers (HBVDNA >6log10 copies/mL). HBeAg‐positive pregnant women either in the second or third trimester were recruited in a prospective, case–control, open‐label study, at the Second Affiliated Hospital of the Southeast University, China (February 2008‐December 2010). Efficacy (month 7: HBVDNA (+), HBsAg (+) infants) in either the overall group or the treated group and control group was analysed using student's t‐test. Infants were followed for at least 1 year. 362 women received LdT (second trimester n = 257; third trimester n = 105) and 92 were untreated. Before delivery, the mean maternal HBVDNA was 2.73, 2.47, 3.34 and 7.94 log10 copies/mL in the overall, second and third trimester treated and control groups, respectively (P < 0.001). At birth, 11.8% of babies overall (43/365), 13.5% (35/259) of those treated in the second trimester, 7.5% of those treated in the third trimester (8/106) and 20.7% (19/92) of untreated infants were HBsAg positive. At month 7, none of the LdT‐treated infant had detectable HBVDNA, while eight infants from control mothers were HBsAg positive. Vertical transmission was 0% in LdT treated and 9.3% (8/86) in the control groups (P < 0.001). No difference in the vertical transmission rate was found in mothers treated in the second or third trimester. LdT treatment was safe for mothers and infants, and no congenital deformities were reported.
Conscious Action/Zombie Action
Authors: Shepherd Joshua
Published: January 2015

I argue that the neural realizers of experiences of trying (that is, experiences of directing effort towards the satisfaction of an intention) are not distinct from the neural realizers of actual trying (that is, actual effort directed towards the satisfaction of an intention). I then ask how experiences of trying might relate to the perceptual experiences one has while acting. First, I assess recent zombie action arguments regarding conscious visual experience, and I argue that contrary to what some have claimed, conscious visual experience plays a causal role for action control in some circumstances. Second, I propose a multimodal account of the experience of acting. According to this account, the experience of acting is (at the very least) a temporally extended, co‐conscious collection of agentive and perceptual experiences, functionally integrated and structured both by multimodal perceptual processing as well as by what an agent is, at the time, trying to do.
An audit of anesthesia safety in a pediatric cochlear implantation program
Authors: Hawksworth Chris , Ravury Shyam
Published: January 2015

Background

Approximately 50 children per year undergo cochlear implant surgery under the Scottish Cochlear Implant Programme at University Hospital Crosshouse, Kilmarnock. Many have significant comorbidities. Although this district general hospital has a high dependency unit, there is no pediatric intensive care unit (PICU). Children deemed likely to need PICU care are operated on at the local tertiary pediatric hospital in Glasgow, 25 miles away.

Objective

To determine the safety of anesthesia for cochlear implant surgery in children at a district general hospital.

Methods

Using the theater management system, we identified 306 cochlear implant procedures in children aged 16 years and under. A retrospective case note review was performed to determine demographic data and seek evidence of any anesthesia‐related complications.

Results

Records for 168 children having 258 cochlear implant procedures were obtained. Forty percent of these children had one or more comorbidities, including 11.9% who were ex‐premature babies. Twenty‐two complications or incidents were noted, the majority of which were minor. Two cases had potentially serious complications and one of these was abandoned. This gives a serious complication rate of 0.8%. Undeclared upper respiratory tract infections was most likely the greatest preventable cause of complications. Seven cases were referred to the regional pediatric center during the study period.

Conclusion

Anesthesia for cochlear implants in children can be safely carried out in a district general hospital setting. Appropriate safeguards should be in place to refer complex cases which may require PICU to a tertiary pediatric center.
Evaluation of Photoprotective Potential and Percutaneous Penetration by Photoacoustic Spectroscopy of the Schinus terebinthifolius Raddi Extract
Authors: Bulla Milena K. , Hernandes Luzmarina , Baesso Mauro L. , Nogueira Ana C. , Bento Antonio C. , Bortoluzzi Bruno B. , Serra Lara Z. , Cortez Diogenes A. G.
Published: January 2015

Schinus terebinthifolius is a plant rich in phenolic compounds, which have antioxidant properties and can provide new opportunities for treatment and prevention of diseases mediated by ultraviolet radiation like photoaging and skin cancer. The aim of this study was to evaluate the photoprotective potential and ex vivo percutaneous penetration of the crude extract of Schinus terebinthifolius leaves. The extract was tested for antioxidant activity using the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) method and β‐carotene bleaching test. The sun protection factor was also evaluated. The ex vivo skin permeation of the emulsion and gel formulations were assayed. Fractionation of the extract resulted in gallic acid, ethyl gallate and a mixture of flavonoids, suggesting derivatives of quercetin and myricetin. The phenolic content of the extract was 384.64 ± 2.60 mg GAE g−1 extract. The antioxidant activity was superior to butylated hydroxytoluene, in DPPH method, and ascorbic acid and rutin, in β‐carotene bleaching assay. The extract showed UV absorption with photoprotector potential in the UVB region. The photoacoustic spectroscopy measurements confirmed absorption in the UV region and topical application of the formulations caused no histological changes in the rats' skin. These results suggest that the crude extract of Schinus terebinthifolius leaves may be a promising natural sunscreen product.
Shade affects responses to drought and flooding – acclimation to multiple stresses in bittersweet (Solanum dulcamara L.)
Authors: Visser E. J. W. , Zhang Q. , De Gruyter F. , Martens S. , Huber H.
Published: January 2015

Plants exposed to environmental stress often respond by a change in their phenotypic traits. These changes in trait expression may alleviate the negative effect of such stress factors. However, if multiple stresses are present, responses are likely to be less predictable and hence do not necessarily correlate to plant performance. This study tested if this expectation was true, by subjecting Solanum dulcamara plants to various simultaneous stress factors. Plants were grown in well‐watered conditions, drought or flooding, and exposed to either full light or shade for 4 weeks. Shoot and root biomass, stem morphological parameters, such as height, number of nodes and length of stem internodes, and leaf traits like length, specific leaf area, chlorophyll content and stomatal conductance were determined. Both variation in light and in water availability typically caused slower growth, and resulted in distinct phenotypic changes in stem, leaf and root traits. However, effects of stresses on the expression of traits were not always additive. Instead, some combined stress responses (e.g. leaf size) appeared to be limited by physical or physiological constraints, whereas other responses were opposite to each other (e.g. root:shoot ratio), resulting in an intermediate phenotype in the combined stress treatment. These data suggest that in natural conditions, where combined stress factors are likely to be present, the optimal phenotype may not necessarily be expressed. Responses of plants to multiple stress factors may therefore not be associated with immediate advantages in terms of increased performance.
Respiratory impedance in healthy unsedated South African infants: Effects of maternal smoking
Authors: Gray Diane , Czövek Dorottya , Smith Emilee , Willemse Lauren , Alberts Ane , Gingl Zoltán , Hall Graham L. , Zar Heather J. , Sly Peter D. , Hantos Zoltán
Published: January 2015

Background and objective

Non‐invasive techniques for measuring lung mechanics in infants are needed for a better understanding of lung growth and function, and to study the effects of prenatal factors on subsequent lung growth in healthy infants. The forced oscillation technique requires minimal cooperation from the individual but has rarely been used in infants. The study aims to assess the use of the forced oscillation technique to measure the influence of antenatal exposures on respiratory mechanics in unsedated infants enrolled in a birth cohort study in Cape Town, South Africa.

Methods

Healthy term infants were studied at 6–10 weeks of age using the forced oscillation technique. Respiratory impedance was measured in the frequency range 8–48 Hz via a face mask during natural sleep. Respiratory system resistance, compliance and inertance were calculated from the impedance spectra.

Results

Of 177 infants tested, successful measurements were obtained in 164 (93%). Median (25–75%) values for resistance, compliance and inertance were 50.2 (39.5–60.6) cmH2O.s.L−1, 0.78 (0.61–0.99) mL.cmH2O−1 and 0.062 (0.050–0.086) cmH2O.s2.L−1, respectively. As a group, male infants had 16% higher resistance (P = 0.006) and 18% lower compliance (P = 0.02) than females. Infants whose mothers smoked during pregnancy had a 19% lower compliance than infants not exposed to tobacco smoke during pregnancy (P = 0.005). Neither maternal HIV infection nor ethnicity had a significant effect on respiratory mechanics.

Conclusions

The forced oscillation technique is sensitive enough to demonstrate the effects of tobacco smoke exposure and sex in respiratory mechanics in healthy infants. This technique will facilitate assessing perinatal influences of lung function in infancy.
Latino and Latina Adolescents' Help‐seeking Behaviors and Attitudes Regarding Suicide Compared to Peers with Recent Suicidal Ideation
Authors: De Luca Susan , Schmeelk‐Cone Karen , Wyman Peter
Published: January 2015

Although Latinas have consistently reported higher rates of suicidal behavior for the past 20 years (CDC, 1996), there is a dearth of information regarding their help‐seeking attitudes and behaviors when dealing with distress and suicide. Associations between adolescents' ideation and help‐seeking from adults were different for non‐Hispanic Whites and Latinos from 14 high schools (N = 4,983). Among females, ideators and Latinas reported lower levels of help‐seeking attitudes than nonideators and non‐Hispanic Whites. Males showed interaction effects of ideation by race/ethnicity on help‐seeking. Within sex by race/ethnicity, differences showed that while non‐Hispanic White students reported consistent differences between suicidal ideation and no reported suicidal ideation, Latinos were more similar between these groups, particularly with having support from friends and family to seek help from adults. Research should clarify how culture contributes to decreased help‐seeking norms among those with suicidal ideation.
Risk factors for pre‐ and post‐engraftment bloodstream infections after allogeneic hematopoietic stem cell transplantation
Authors: Kikuchi M. , Akahoshi Y. , Nakano H. , Ugai T. , Wada H. , Yamasaki R. , Sakamoto K. , Kawamura K. , Ishihara Y. , Sato M. , Ashizawa M. , Terasako‐Saito K. , Kimura S. , Yamazaki R. , Kanda J. , Kako S. , Nishida J. , Kanda Y.
Published: January 2015

Background

Bloodstream infections (BSI) are frequently observed after allogeneic hematopoietic stem cell transplant (HSCT), and could cause morbidity and mortality.

Methods

We retrospectively evaluated the incidence, characteristics of, and risk factors for BSI at both pre‐ and post‐engraftment in 209 adult HSCT patients at our institute between June 2006 and December 2013. The median age at transplantation was 45 years (range, 15–65). A total of 122 patients received bone marrow, 68 received peripheral blood stem cells, and 19 received umbilical cord blood.

Results

The cumulative incidences of pre‐ and post‐engraftment BSI were 38.9% and 17.2%, respectively. Nine patients had both pre‐ and post‐engraftment BSI. In the pre‐ and post‐engraftment periods, respectively, 67.4% and 84.1% of isolates were gram‐positive bacteria (GPB), 28.3% and 11.4% were gram‐negative bacteria (GNB), and 4.3% and 4.5% were fungi. Coagulase‐negative staphylococci were the most commonly isolated GPB, while Stenotrophomonas maltophilia and Pseudomonas aeruginosa were the most commonly isolated GNB. Pre‐engraftment BSI was associated with an increased risk of death. Overall survival at day 180 for patients with or without pre‐engraftment BSI was 70.0% and 82.7%, respectively (P = 0.02).

Conclusions

Risk factors for BSI in the pre‐engraftment period were the interval between diagnosis and transplantation (261 days or more), engraftment failure, and high‐risk disease status at HSCT in a multivariate analysis. No significant risk factor for BSI in the post‐engraftment period was identified by a univariate analysis. These findings may be useful for deciding upon empiric antibacterial treatment for HSCT recipients.
Foreign Market Entry Under Incomplete Contracts
Authors: Seidel Tobias
Published: January 2015

This paper shows that incomplete contracts serve as a determinant of the mode of foreign market entry – that is exports versus foreign direct investment (FDI). When contracts between two agents within a firm are too costly to be written, the share of multinational firms may be higher or lower compared with a world without contractual frictions. The direction of change depends on the technologically required relative contribution of headquarter services in the joint production process. For example, in industries that use more inputs from the management unit as compared to inputs from a component supplier, the share of firms engaging in foreign direct investment is higher than under complete contracts. This effect may be so strong that the share of multinational firms increases in trade freeness.
Angiotensin II can directly induce mitochondrial dysfunction, decrease oxidative fibre number and induce atrophy in mouse hindlimb skeletal muscle
Authors: Kadoguchi Tomoyasu , Kinugawa Shintaro , Takada Shingo , Fukushima Arata , Furihata Takaaki , Homma Tsuneaki , Masaki Yoshihiro , Mizushima Wataru , Nishikawa Mikito , Takahashi Masashige , Yokota Takashi , Matsushima Shouji , Okita Koichi , Tsutsui Hiroyuki
Published: January 2015

New findings

What is the central question of this study?

Does angiotensin II directly induce skeletal muscle abnormalities?

What is the main finding and its importance?

Angiotensin II induces skeletal muscle abnormalities and reduced exercise capacity. Mitochondrial dysfunction and a decreased number of oxidative fibres are manifest early, while muscle atrophy is seen later. Thus, angiotensin II may play an important role in the skeletal muscle abnormalities observed in a wide variety of diseases.

Skeletal muscle abnormalities, such as mitochondrial dysfunction, a decreased percentage of oxidative fibres and atrophy, are the main cause of reduced exercise capacity observed in ageing and various diseases, including heart failure. The renin–angiotensin system, particularly angiotensin II (Ang II), is activated in the skeletal muscle in these conditions. Here, we examined whether Ang II could directly induce these skeletal muscle abnormalities and investigated their time course. Angiotensin II (1000 ng kg−1 min−1) or vehicle was administered to male C57BL/6J mice (10–12 weeks of age) via subcutaneously implanted osmotic minipumps for 1 or 4 weeks. Angiotensin II significantly decreased body and hindlimb skeletal muscle weights compared with vehicle at 4 weeks. In parallel, muscle cross‐sectional area was also decreased in the skeletal muscle at 4 weeks. Muscle RING finger‐1 and atrogin‐1 were significantly increased in the skeletal muscle from mice treated with Ang II. In addition, cleaved caspase‐3 and terminal deoxynucleotidyl trasferase‐mediated dUTP nick‐positive nuclei were significantly increased in mice treated with Ang II at 1 and 4 weeks, respectively. Mitochondrial oxidative enzymes, such as citrate synthase, complex I and complex III activities were significantly decreased in the skeletal muscle from mice treated Ang II at 1 and 4 weeks. NAD(P)H oxidase‐derived superoxide production was increased. NADH staining revealed that type I fibres were decreased and type IIb fibres increased in mice treated with Ang II at 1 week. The work and running distance evaluated by a treadmill test were significantly decreased in mice treated with Ang II at 4 weeks. Thus, Ang II could directly induce the abnormalities in skeletal muscle function and structure.
Interactions between mitochondria and the transcription factor myocyte enhancer factor 2 (MEF2) regulate neuronal structural and functional plasticity and metaplasticity
Authors: Brusco Janaina , Haas Kurt
Published: January 2015

The classical view of mitochondria as housekeeping organelles acting in the background to simply maintain cellular energy demands has been challenged by mounting evidence of their direct and active participation in synaptic plasticity in neurons. Time‐lapse imaging has revealed that mitochondria are motile in dendrites, with their localization and fusion and fission events regulated by synaptic activity. The positioning of mitochondria directly influences function of nearby synapses through multiple pathways including control over local concentrations of ATP, Ca2+ and reactive oxygen species. Recent studies have also shown that mitochondrial protein cascades, classically associated with apoptosis, are involved in neural plasticity in healthy cells. These findings link mitochondria to the plasticity‐ and metaplasticity‐associated activity‐dependent transcription factor myocyte enhancer factor 2 (MEF2), further repositioning mitochondria as potential command centres for regulation of synaptic plasticity. Intriguingly, MEF2 and mitochondrial functions appear to be intricately intertwined, as MEF2 is a target of mitochondrial apoptotic caspases and, in turn, MEF2 regulates mitochondrial genome transcription essential for production of superoxidase and hydrogen peroxidase. Here, we review evidence supporting mitochondria as central organelles controlling the spatiotemporal expression of neuronal plasticity, and attempt to disentangle the MEF2–mitochondria relationship mediating these functions.
Protease‐activated receptors modulate excitability of murine colonic smooth muscles by differential effects on interstitial cells
Authors: Sung Tae Sik , Kim Heung Up , Kim Jeong Hwan , Lu Hongli , Sanders Kenton M. , Koh Sang Don
Published: January 2015

Key points

Activation of protease‐activated receptors (PAR) regulates gastrointestinal (GI) motility but little is known about the cells and mechanisms in GI muscles responsible for PAR responses.

Using mouse cells, we found high levels of F2r and F2rl1 PAR‐encoding genes expressed in purified platelet‐derived growth factor α‐positive (PDGFRα+) cells in comparison to other cells in colonic muscles.

PAR1 and PAR2 agonists caused transient hyperpolarization and relaxation of colonic muscles, with relaxation responses followed by excitation.

The inhibitory phase was inhibited by apamin and mediated by activation of small conductance calcium‐activated potassium channels in PDGFRα+ cells.

The excitatory response resulted largely from activation of a chloride conductance in interstitial cells of Cajal; small amplitude inward currents were generated in smooth muscle cells by PAR activation, but these responses were too small to be resolved in intact muscles.

PAR receptor responses are integrated responses generated by cells of the smooth muscle, interstitial cells of Cajal and PDGFRα+ cells (SIP syncytium).

Protease‐activated receptors (PARs) are G protein‐coupled receptors activated by proteolytic cleavage at their amino termini by serine proteases. PAR activation contributes to the inflammatory response in the gastrointestinal (GI) tract and alters GI motility, but little is known about the specific cells within the tunica muscularis that express PARs and the mechanisms leading to contractile responses. Using real time PCR, we found PARs to be expressed in smooth muscle cells (SMCs), interstitial cells of Cajal (ICC) and platelet‐derived growth factor receptor α positive (PDGFRα+) cells. The latter cell‐type showed dominant expression of F2r (encodes PAR1) and F2rl1 (encodes PAR2). Contractile and intracellular electrical activities were measured to characterize the integrated responses to PAR activation in whole muscles. Cells were isolated and ICC and PDGFRα+ cells were identified by constitutive expression of fluorescent reporters. Thrombin (PAR1 agonist) and trypsin (PAR2 agonist) caused biphasic responses in colonic muscles: transient hyperpolarization and relaxation followed by repolarization and excitation. The inhibitory phase was blocked by apamin, revealing a distinct excitatory component. Patch clamp studies showed that the inhibitory response was mediated by activation of small conductance calcium‐activated K+ channels in PDGFRα+ cells, and the excitatory response was mediated by activation of a Cl− conductance in ICC. SMCs contributed little to PAR responses in colonic muscles. In summary, PARs regulate the excitability of colonic muscles; different conductances are activated in each cell type of the SMC–ICC–PDGFRα+ cell (SIP) syncytium. Motor responses to PAR agonists are integrated responses of the SIP syncytium.
The influence of sensory afferent input on local motor cortical excitatory circuitry in humans
Authors: Cash Robin F. H. , Isayama Reina , Gunraj Carolyn A. , Ni Zhen , Chen Robert
Published: January 2015

Key points

In the human, sensorimotor integration can be investigated using combined sensory and transcranial magnetic stimulation (TMS).

Short latency afferent inhibition (SAI) refers to motor cortical inhibition 20–25ms after median nerve stimulation.

We investigated the influence of SAI on a local excitatory interneuronal motor cortical circuit known as short‐interval intracortical facilitation (SICF) and found that, contrary to expectations, SICF was facilitated in the presence of SAI (SICFSAI); this effect is specific to SICF since there was no effect in control conditions in which SICF was not elicited, and the facilitatory SICFSAI interaction increased with increasing strength of SICF or SAI.

The influence of sensory input on excitatory motor cortical circuitry was similar across different bodily regions, different circuits within motor cortex and across functional states, suggesting that this interaction may have general applicability in sensorimotor integration and motor control.

SAI and SICF were found to correlate between individuals in that those with high SAI were found to have high SICF, and this relationship was maintained when SICF was delivered in the presence of SAI, suggesting an intrinsic relationship between SAI and SICF; these findings are compatible with brain‐slice studies of sensorimotor circuitry and add to our understanding of sensorimotor integration.

In human, sensorimotor integration can be investigated by combining sensory input and transcranial magnetic stimulation (TMS). Short latency afferent inhibition (SAI) refers to motor cortical inhibition 20–25 ms after median nerve stimulation. We investigated the interaction between SAI and short‐interval intracortical facilitation (SICF), an excitatory motor cortical circuit. Seven experiments were performed. Contrary to expectations, SICF was facilitated in the presence of SAI (SICFSAI). This effect is specific to SICF since there was no effect at SICF trough 1 when SICF was absent. Furthermore, the facilitatory SICFSAI interaction increased with stronger SICF or SAI. SAI and SICF correlated between individuals, and this relationship was maintained when SICF was delivered in the presence of SAI, suggesting an intrinsic relationship between SAI and SICF in sensorimotor integration. The interaction was present at rest and during muscle contraction, had a broad degree of somatotopic influence and was present in different interneuronal SICF circuits induced by posterior–anterior and anterior–posterior current directions. Our results are compatible with the finding that projections from sensory to motor cortex terminate in both superficial layers where late indirect (I‐) waves are thought to originate, as well as deeper layers with more direct effect on pyramidal output. This interaction is likely to be relevant to sensorimotor integration and motor control.
Feasibility of Shape Memory Alloy Wire Actuation for an Active Steerable Cannula
Authors: Konh Bardia , Datla Naresh V. , Hutapea Parsaoran
Published: January 2015

Needle insertion is used in many diagnostic and therapeutic percutaneous medical procedures such as brachytherapy, thermal ablations, and breast biopsy. Insufficient accuracy using conventional surgical cannulas motivated researchers to provide actuation forces to the cannula's body for compensating the possible errors of surgeons/physicians. In this study, we present the feasibility of using shape memory alloy (SMA) wires as actuators for an active steerable surgical cannula. A three-dimensional (3D) finite element (FE) model of the active steerable cannula was developed to demonstrate the feasibility of using SMA wires as actuators to bend the surgical cannula. The material characteristics of SMAs were simulated by defining multilinear elastic isothermal stress–strain curves that were generated through a matlab code based on the Brinson model. Rigorous experiments with SMA wires were done to determine the material properties as well as to show the capability of the code to predict a stabilized SMA transformation behavior with sufficient accuracy. In the FE simulation, birth and death method was used to achieve the prestrain condition on SMA wire prior to actuation. This numerical simulation was validated with cannula deflection experiments with developed prototypes of the active cannula. Several design parameters affecting the cannula's deflection such as the cannula's Young's modulus, the SMA's prestrain, and its offset from the neutral axis of the cannula were studied using the FE model. Real-time experiments with different prototypes showed that the quickest response and the maximum deflection were achieved by the cannula with two sections of actuation compared to a single section of actuation. The numerical and experimental studies showed that a highly maneuverable active cannulas can be achieved using the actuation of multiple SMA wires in series.