bluuebunny/crossref_metadata_2025 huggingface dataset:
Aquaporin 4 expression on trigeminal satellite glial cells under normal and inflammatory conditions
Authors: Riccio D. , Magni G. , Ceruti S. , Arendt-Nielsen L. , Gazerani P.
Published: August 2017

Aims

Limited information is currently available for the expression and role of Aquaporin 4 (AQP4) (AQ4) in the peripheral nervous system (PNS). It has been demonstrated that AQP4 is expressed in sensory ganglia. Immunohistochemistry has revealed that satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in these sensory ganglia exclusively express AQP4 at a considerably lower level than what is seen in astrocytes. The pathophysiological relevance of AQP4 in peripheral nociception; however, remains unclear. Hence, this study aimed at investigating AQP4 expression in trigeminal neurons and SGCs under normal and inflammatory conditions relevant to craniofacial pain conditions.

Methods

Rat trigeminal ganglia (TG) were isolated from adult male Sprague-Dawley rats subjected to a model of trigeminal inflammation evoked by unilateral complete Freund’s adjuvant (CFA) injection in temporomandibular joint. Immunohistochemistry was performed on TG sections of CFA-treated animals. NeuN and GS markers were used for identification of neurons and SGCs, respectively. AQP4 expression was investigated in both ipsilateral and contralateral TG sections. The study protocol was approved by the local ethics committee.

Results

Co-localization of NeuN-AQP4 and GS-AQP4 were identified in both ipsi and contralateral trigeminal ganglia of the CFA-treated rats. However, we did not detect any difference between the ipsi- and contralateral side in terms of alteration in AQP4 receptor expression.

Conclusions

AQP4 was expressed both on trigeminal neurons and SGCs and CFA did not cause a remarkable change in AQP4 expression, when ipsilateral and contralateral TG of the test animals was compared. Previously, it has been shown that in a neuropathic pain model no difference is detectable between wild type and AQP4-deficient mice, for mechanical and thermal perception; however, in formalin pain model AQP4-deficient mice have higher thermal pain thresholds. Further investigation is required to clarify role of AQP4 in pain.
Biomarkers alterations in trapezius muscle after an acute tissue trauma: A human microdialysis study
Authors: Sørensen L.B. , Gazerani P. , Wåhlén K. , Ghafouri N. , Gerdle B. , Ghafouri B.
Published: August 2017

Aims

Alteration in muscle milieu has been proposed as one of the main contributors underlying chronic musculoskeletal pain (CMP). Microdialysis (MD) provides real-time information on release of pain and metabolic biomarkers in muscle. However, insertion of MD probe causes a local tissue trauma, which may affect the tissue milieu. Whether an acute tissue trauma alter pain and metabolite biomarkers in trapezius muscle of patients with CMP is not known. Hence, this study investigated changes in muscle metabolites following MD probe insertion in patients with CMP in comparison with healthy controls.

Methods

Nineteen patients (11 women and 8 men; 41.4 years) with CMP and 20 pain-free volunteers (10 women and 10 men; 36.5 years) were recruited (project approval number: 2013/151- 31). Baseline pressure pain thresholds (PPT) at trapezius muscle were obtained bilaterally with a reference point at the tibialis muscle. Pain questionnaires were used for determining levels of anxiety and depression and catastrophizing impact. Interstitial samples were collected from trapezius muscles by aid of MD (20 kDa cut-off) during a period of 40 min. Collected dialysates at 2 time-points of 20 and 40 min were stored at −70 °C until analysis. Concentrations of glucose, lactate, pyruvate, glycerol, and glutamate were analyzed by ISCUSSflex. P ≤ 0.05 was considered significant.

Results

No potential case with respect to anxiety, depression or catastrophizing impact was found. Lower PPTs were found in CMP group (P ≤ 0.05). Significantly lower levels of pyruvate were found in CMP group at both 20 min (P = 0.003) and 40 min (P = 0.006). Gender-based analysis indicated higher concentrations of glutamate in female patients with CMP.

Conclusions

This study was first to demonstrate metabolite alterations during trauma phase of MD in trapezius muscles of CPM compared with healthy controls. This model proved beneficial for investigating pain and metabolic biomarkers during acute phase of MD.
Drugs that can cause respiratory depression with concomitant use of opioids
Authors: Sigmarsdottir B.D. , Gudmundsdottir Th.K. , Zoäga S. , Gunnarsson P.S.
Published: August 2017

Aims

Respiratory depression is a serious life threatening condition and a known adverse event of opioids. Little is known about the use of the opioid antidote naloxon in Iceland, and the additive effects of other potentially respiratory depressive drugs administered with opioids. The aim of the study was to review the literature on drugs that may cause respiratory depression and to assess medication use in patients receiving parenteral naloxone in Landspítali University Hospital.

Methods

A review and analysis of drugs that can cause respiratory depression based on information from the scientific literature, medicine databases and clinical guidelines. A retrospective study was performed using data collected from the electronic medical records system of Landspítali University Hospital for all patients, 18 years and older that had parenteral naloxon administered in the years 2010–2014. Information about the type of opioid and other respiratory depressive drugs was collected and the data was further investigated in regards to age, gender, and type of service.

Results

The most potential drugs and drug classes that can cause respiratory depression when used concomitantly with opioids are benzodiazepines and other anxiolytics, hypnotics and sedatives, antipsychotics, antiepileptics, antihistamins and anesthetics. When use was examined (N=138) morphine was the most frequent opioid given (49%). Concomitant use of opioids and other respiratory depressive drugs was seen in 63% of cases, and benzodiazepines were the most frequent drugs given with opioids (33%).

Conclusions

The concomitant use of benzodiazepines and other sedative drugs with opioids is frequent, despite the known risk of additive respiratory depression as described in the literature. Other patient risk factors such as medical condition, general health and consciousness should be considered in context with drugs used.
Modelling activity-dependent changes of velocity in C-fibers
Authors: Tigerholm J. , Petersson M.E. , Obreja O. , Lampert A. , Carr R. , Schmelz M. , Fransén E.
Published: August 2017

Aims

When C-nociceptors are activated repeatedly using electrical stimulation at relatively low frequencies (0.125–2 Hz), their propagation velocity will decrease. This is referred to as activity-dependent slowing (ADS). The main reason why activity-dependent changes in velocity are of interest is that they can be recorded directly, using invasive methods (microneurography), in patients with chronic pain. Interestingly, in certain patients with neuropathic pain, reduced activity-dependent slowing of conduction has been observed, indicating that these axons have an increased excitability. Through a computational model, it is possible to link such velocity alterations with changes in active conductances, opening for an understanding the underlying excitability changes occurring in these patients.

Methods

We have developed a detailed multicompartment model of a C-nociceptor fiber. This model incorporates a wide range of voltage-gated ion channels (Nav1.7, Nav1.8, Nav1.9, K
dr, K
A, K
M, K
Na and h) which were implemented across a detailed and realistic axon morphology.

Results

The model predicts that the small diameter of the axon can accumulate intracellular sodium when it is repeatedly activated in a similar fashion as during single fiber microneurography. This increase of intracellular sodium concentration can shift the balance between ion channel currents, shift the membrane potential and membrane input resistance, and thereby generate activity-dependent changes of velocity, such as ADS as well as recovery cycle supernormality.

Conclusions

Our results thus provide insight into how activity-dependent excitability changes can be generated in C-fibers. By identifying which ion channels are contributing to activity-dependent changes of velocity this could provide insight into ion channel alterations in neuropathic pain patients.
Omics as a potential tool to identify biomarkers and to clarify the mechanism of chronic pain development
Authors: Gerra M.C. , Dagostino C. , D’Agnelli S. , Boggiani L. , Rizza V. , Marchesini M. , Allegri M. , Fanelli G.
Published: August 2017

Aims

The present study aims to identify the underlying mechanisms in the acute to chronic pain transition. Acute pain is a physiological response to an experience of noxious stimuli that can progress to chronic, becoming a disease. The negative consequences as personal suffering, reduction in physical function, maladaptive behaviours, reduction of productivity, make this condition a central and common problem affecting individuals and the society. After an acute damage, pain in some cases persists, being the process attributed to different causes, in particular persistent tissue and neuronal damages, central neuroplastic changes, psychosocial factors.

Methods

The techniques actually used to investigate acute and chronic pain offer only a partial explanation of the process and in addition, the obtained results are often far away from the possibility to lead some benefits in the clinical practice. Omics technologies could be the right way to detect biomarkers explaining these mechanisms. Our previous study examined epigenetic and pharmacogenetic aspects of acute and chronic pain in a large group of patients. Other omic approaches, such as metabolomics and glycomics, could help to (1) better identify metabolites that can serve as chronic pain development or side effects therapy biomarkers and to (2) better understand new insights involved into the pathophysiological mechanism that drives from acute to chronic pain. SNPs, DNA methylation, miRNA analyses, expression and protein assays on the identified pathway would than clarify the causative molecular mechanisms. In addition, linking these results to clinical evaluation of the central sensitization processes through algometry in nociceptive and neuropathic pain patients may reveal crucial clinical and pharmacological implications.

Conclusions

Our project will be implemented by omic technologies in different chronic pain patient cohorts (acute low back pain vs chronic low back pain patients and chronic postsurgical pain patients) in order to evaluate new possible pathophysiological mechanism with special focus in central sensitization.
A novel hybrid back-stepping and fuzzy logic control strategy for a quadcopter
Authors: Shraim H. , Harkouss Y. , Bazzi H.
Published: August 2017

This article aims to present a novel control strategy for quadrotor helicopter. It is composed of three main parts constituting the system modelling, the integral back-stepping control, and fuzzy logic compensator. In the first part, a non-linear model is presented taking in consideration some non-linearities and variables that are usually neglected. In the second part, a controller based on the integral back-stepping algorithm has been developed for the system in order to make the system follows a desired path. However, due to complexity of paths and to the presence of unknown disturbances, a fuzzy logic compensator is added in parallel to the integral back-stepping controller to improve trajectory tracking in some critical conditions (high wind speed, mass variation, etc.). Simulation results have been presented to show the effectiveness of the proposed approach.
Rules and Monitoring Systems – Complementary or Conflicting Logics?: A Response to Fleur Johns
Authors: Mallard Grégoire
Published: August 2017

In the last century, international law expanded to new domains that had traditionally fallen under exclusive governmental authority—such as human rights, environmental law, nonproliferation law, trade law, etc. This expansion of international rules coalesced into transnational legal fields, which not only include norms, rules, and procedures, but also monitoring systems designed to ensure compliance by member states and private actors. By assuming that all levels of a legal regime (from norms to rules and procedures, and then to monitoring systems and sanctioning mechanisms in case of observed violations) function in a harmonious and complementary way—as the apparatus of international law is supposed to—, some international law scholars may be tempted to avoid spending time analyzing the technical operations of monitoring agencies. The perusal of inspection and compliance manuals is less rewarding and more taxing than the analysis of preambles of treaties and conventions, where norms of good conduct, allocation of rights, and formal authority between institutions are usually delineated.
Asymptotically based self-similarity solution of the Navier–Stokes equations for a porous tube with a non-circular cross-section
Authors: Bouyges M. , Chedevergne F. , Casalis G. , Majdalani J.
Published: August 2017

This work introduces a similarity solution to the problem of a viscous, incompressible and rotational fluid in a right-cylindrical chamber with uniformly porous walls and a non-circular cross-section. The attendant idealization may be used to model the non-reactive internal flow field of a solid rocket motor with a star-shaped grain configuration. By mapping the radial domain to a circular pipe flow, the Navier–Stokes equations are converted to a fourth-order differential equation that is reminiscent of Berman’s classic expression. Then assuming a small radial deviation from a fixed chamber radius, asymptotic expansions of the three-component velocity and pressure fields are systematically pursued to the second order in the radial deviation amplitude. This enables us to derive a set of ordinary differential relations that can be readily solved for the mean flow variables. In the process of characterizing the ensuing flow motion, the axial, radial and tangential velocities are compared and shown to agree favourably with the simulation results of a finite-volume Navier–Stokes solver at different cross-flow Reynolds numbers, deviation amplitudes and circular wavenumbers.
Tectonic and climatic controls on the late Pleistocene to Holocene evolution of Paleolake Ullum-Zonda in the Precordillera of the central Andes, Argentina
Authors: Blanc Pablo A. , Perucca Laura P.
Published: August 2017

The Ullum-Zonda tectonic depression located in the central Andes Precordillera records several lacustrine episodes from frequent natural damming of the San Juan River during the late Quaternary. We analyzed stratigraphic, geomorphic, and geologic data and obtained new radiocarbon ages for Paleolake Ullum-Zonda. Results show the existence of a late Pleistocene age (16.7–15.2 ka BP) unit and an early to middle Holocene (9475–7685 yr BP) unit. Subsurface data show lacustrine episodes were common during the late Pleistocene, with probably nine episodes occurring during that period. Two transgressive events are evident in the Holocene unit, dated to ~8420±30 and shortly after 7460±30 14C yr BP. The maximum extent of the paleolake occurred at 6930±30 14C yr BP, shortly before the lake desiccated. Fault propagation folds and growth strata in Quaternary alluvial deposits relate to the Villicum-Zonda Fault and may indicate early to middle Holocene activity for this fault. The deformation observed in an ancient shoreline of the paleolake could be related to middle to late Holocene activity of the Cerro Zonda Norte Fault at a mean vertical uplift rate of ~0.8 mm/yr in the hanging wall block.
Raciolinguistic ideology and Spanish-English bilingualism on the US labor market: An analysis of online job advertisements
Authors: Subtirelu Nicholas Close
Published: August 2017

Multilingualism is often framed as human capital that increases individuals’ labor market value. Such assertions overlook the role of ideology in assigning value to languages and their speakers based on factors other than communicative utility. This article explores the value assigned to Spanish-English bilingualism on the United States labor market through a mixed methods analysis of online job advertisements. Findings suggest that Spanish-English bilingualism is frequently preferred or required for employment in the US, but that such employment opportunities are less lucrative. The results suggest a penalty associated with Spanish-English bilingualism in which positions listing such language requirements advertise lower wages than observationally similar positions. Quantitative disparities and qualitative differences in the specification of language requirements across income levels suggest that bilingual labor is assigned value through a racial lens that leads to linguistic work undertaken by and for US Latinxs being assigned less value. (Multilingualism, labor market, Spanish in the United States, economics of language, raciolinguistics, human capital)*
How to compare performance of robust design optimization algorithms, including a novel method
Authors: Persson Johan A. , Ölvander Johan
Published: August 2017

This paper proposes a method to compare the performances of different methods for robust design optimization of computationally demanding models. Its intended usage is to help the engineer to choose the optimization approach when faced with a robust optimization problem. This paper demonstrates the usage of the method to find the most appropriate robust design optimization method to solve an engineering problem. Five robust design optimization methods, including a novel method, are compared in the demonstration of the comparison method. Four of the five compared methods involve surrogate models to reduce the computational cost of performing robust design optimization. The five methods are used to optimize several mathematical functions that should be similar to the engineering problem. The methods are then used to optimize the engineering problem to confirm that the most suitable optimization method was identified. The performance metrics used are the mean value and standard deviation of the robust optimum as well as an index that combines the required number of simulations of the original model with the accuracy of the obtained solution. These measures represent the accuracy, robustness, and efficiency of the compared methods. The results of the comparison show that sequential robust optimization is the method with the best balance between accuracy and number of function evaluations. This is confirmed by the optimizations of the engineering problem. The comparison also shows that the novel method is better than its predecessor is.
Brain abscesses in children: an Italian multicentre study
Authors: RAFFALDI I. , GARAZZINO S. , CASTELLI GATTINARA G. , LIPRERI R. , LANCELLA L. , ESPOSITO S. , GIANNINI A. M. , MONTAGNANI C. , MARSEGLIA G. L. , PIGNATA C. , BERNARDI F. , TOVO P.-A. ,   SITIP BRAIN ABSCESSES REGISTRY
Published: August 2017

Brain abscess is uncommon in paediatric population, but of clinical importance because of significant long-term morbidity and mortality. In this multicentre study, promoted by the Italian Society for Paediatric Infectious Diseases, we retrospectively collected patients aged 0–18 years, with a diagnosis of ‘brain abscess’. Seventy-nine children were included; the median age was 8·75 years. As predisposing factor, 44 children had preceding infections. The Gram-positive cocci were mostly isolated (27 cases). Sixty (76%) children underwent a surgical intervention. Intravenous antibiotic therapy was administered in all patients, then switched to oral treatment. Clinical sequelae were recorded in 31 (39·2%) children. Twenty-one of them had a single sequela, of which, the most represented, was epilepsy in nine of them. This study focus the attention on the need to have standardized national guidelines or adequate recommendations on type and duration of antibiotic treatment.
The high frequency of non-aspartic acid residues at HA222 in influenza A(H1N1) 2009 pandemic viruses is associated with mortality during the upsurge of 2015: a molecular and epidemiological study from central India
Authors: BARDE P. V. , SAHU M. , SHUKLA M. K. , BHARTI P. K. , SHARMA R. K. , SAHARE L. K. , UKEY M. J. , SINGH N.
Published: August 2017

Influenza A(H1N1) viruses of the 2009 pandemic (A(H1N1)pdm09) continue to cause outbreaks in the post-pandemic period. During January to May 2015, an upsurge of influenza was recorded that resulted in high fatality in central India. Genetic lineage, mutations in the hemagglutinin (HA) gene and infection by quasi-species are reported to affect disease severity. The objective of this study is to present the molecular and epidemiological trends during the 2015 influenza outbreak in central India. All the referred samples were subjected to qRT–PCR for diagnosis. HA gene sequencing (23 survivors and 24 non-survivors) and cloning were performed and analyzed using Molecular Evolutionary Genomic Analyzer (MEGA 5·05). Of the 3625 tested samples, 1607 (44·3%) were positive for influenza A(H1N1)pdm09, of which 228 (14·2%) individuals succumbed to death. A significant trend was observed in positivity (P= 0·003) and mortality (P< 0·0001) with increasing age. The circulating A(H1N1)pdm09 virus was characterized as belonging to clade-6B. Clinically significant mutations were detected. Patients infected with the quasi-species of the virus had a greater risk of death (P= 0·009). This study proposes a robust molecular and clinical surveillance program for the detection and characterization of the virus, along with prompt treatment protocols to prevent outbreaks.
Estimation of the transmission dynamics of African swine fever virus within a swine house
Authors: NIELSEN J. P. , LARSEN T. S. , HALASA T. , CHRISTIANSEN L. E.
Published: August 2017

The spread of African swine fever virus (ASFV) threatens to reach further parts of Europe. In countries with a large swine production, an outbreak of ASF may result in devastating economic consequences for the swine industry. Simulation models can assist decision makers setting up contingency plans. This creates a need for estimation of parameters. This study presents a new analysis of a previously published study. A full likelihood framework is presented including the impact of model assumptions on the estimated transmission parameters. As animals were only tested every other day, an interpretation was introduced to cover the weighted infectiousness on unobserved days for the individual animals (WIU). Based on our model and the set of assumptions, the within- and between-pen transmission parameters were estimated toβw= 1·05 (95% CI 0·62–1·72),βb= 0·46 (95% CI 0·17–1·00), respectively, and the WIU = 1·00 (95% CI 0–1). Furthermore, we simulated the spread of ASFV within a pig house using a modified SEIR-model to establish the time from infection of one animal until ASFV is detected in the herd. Based on a chosen detection limit of 2·55% equivalent to 10 dead pigs out of 360, the disease would be detected 13–19 days after introduction.
Effect of high-dose oral cholecalciferol on cardiac mechanics in children with chronic kidney disease
Authors: Deveci Murat , Aytaç Mehmet Baha , Altun Gürkan , Kayabey Özlem , Babaoğlu Kadir
Published: August 2017

Cardiovascular factors are an important cause of mortality in chronic kidney disease, and vitamin-D deficiency is common in this patient population. Therefore, we aimed to investigate the effect of oral cholecalciferol on cardiac mechanics in children with chronic kidney disease. A total of 41 children with chronic kidney disease – the patient group – and 24 healthy subjects – the control group – free of any underlying cardiac or renal disease with low 25-hydroxyvitamin-D3 levels were evaluated by conventional tissue Doppler imaging and two-dimensional speckle-tracking echocardiography, both at baseline and following Stoss vitamin-D supplementation. Left ventricular strain and strain rate values were compared between the study groups. Initial longitudinal and radial strain as well as strain rate values of the left ventricle were significantly lower in patients. After vitamin-D supplementation, these improved significantly in patients, whereas no significant change was observed in the control group. Our study showed that, although conventional and tissue Doppler imaging methods could not determine any effect, two-dimensional speckle-tracking echocardiography revealed the favourable effects of high-dose cholecalciferol on cardiac mechanics, implying the importance of vitamin-D supplementation in children with chronic kidney disease.
Infant feeding decisions and behaviours among low-income smoke-exposed women: timing and change during pregnancy
Authors: Risica Patricia Markham , McCausland Kristen
Published: August 2017

Objective

The present study aimed to describe change in feeding intentions and predictors of breast-feeding intentions during the course of pregnancy.

Design

Analysis of prospectively collected data from a larger randomized controlled trial of a health education intervention to reduce environmental smoke exposure among women during and after pregnancy.

Setting

Participants were recruited from prenatal clinics, but all further communication occurred with participating women living in the community.

Subjects

Low-income, adult women (n399) were interviewed during the 16th and 32nd week of pregnancy to ascertain prenatal feeding intentions and breast-feeding knowledge, attitudes and self-efficacy. Characteristics of women by infant feeding intention were assessed along with differences in intention from 16 to 32 weeks of pregnancy and feeding behaviours after delivery. Differences in psychosocial variables between women of different intention for infant feeding were measured. Women in each category of feeding intention were assessed for changes in psychosocial factors by eventual infant feeding behaviour.

Results

Feeding intention early in pregnancy was strongly, but not consistently, associated with feeding intention late in pregnancy, feeding initiation and later feeding patterns. Over one-third of women who were undecided at 16 weeks’ gestation or earlier initiated breast-feeding. Increases in knowledge and improvement in time, social factors and social support barriers were found among those who exclusively breast-fed.

Conclusions

Results indicate that feeding decisions may change during pregnancy. Determining when women make feeding decisions during their pregnancy warrants more research. Interventions to increase breast-feeding intentions should target knowledge, self-efficacy and barriers.
Exploring beliefs about dietary supplement use: focus group discussions with Dutch adults
Authors: Pajor Emília Margit , Oenema Anke , Eggers Sander Matthijs , de Vries Hein
Published: August 2017

Objective

Although dietary supplement use is increasing in Europe and the USA, little research involving adults’ beliefs regarding dietary supplements has been conducted. Therefore, the present study aimed to explore and compare users’ and non-users’ beliefs towards dietary supplements.

Design

Thirteen focus group discussions were conducted of which seven groups were dietary supplement users and six groups were non-users. Based on the socio-cognitive factors of the Integrated Change Model, a semi-structured topic guide was set up. The discussions were audio-recorded and subjected to qualitative content analysis, applying the framework approach.

Setting

Data were collected in Maastricht, the Netherlands, in 2014 and 2015.

Subjects

In total fifty-six individuals participated in the study, of whom twenty-eight were dietary supplement users and twenty-eight non-users. The average age of participants was 42·9 years.

Results

Dietary supplement users’ attitude beliefs were mainly related to mental and physical health enhancement, illness prevention and curative health benefits. Users were critical of the nutritional knowledge of health professionals and of the quality of food products. Non-users were convinced that the human body does not need any support and that regular food is enough to cover one’s nutritional needs. Users and non-users held comparable beliefs regarding the definition and risks of dietary supplements, and perceived social influences.

Conclusions

In their decision about dietary supplement use, both groups were guided by their own convictions to a great extent. Both groups would benefit from improved understanding of the health effects of dietary supplements to improve informed decision making.
Implication of our technological species being first and early
Authors: Whitmire Daniel P.
Published: August 2017

According to the Principle of Mediocrity, a cornerstone of modern cosmology, in the absence of any evidence to the contrary, we should believe that we are a typical member of an appropriately chosen reference class. If we assume that this principle applies to the reference class of all extant technological species, then it follows that other technological species will, like us, typically find that they are both the first such species to evolve on their planet and also that they are early in their potential technological evolution. Here we argue that this suggests that the typical technological species becomes extinct soon after attaining a modern technology and that this event results in the extinction of the planet's global biosphere.
Psychotherapeutische Interventionen für suizidale Jugendliche – eine systematische Übersicht aktueller Publikationen
Authors: Brown Rebecca C.
Published: August 2017

Zusammenfassung. Obwohl suizidale Gedanken und Verhaltensweisen bei Jugendlichen ein häufiges Phänomen sind, wird die Datenlage zur Evaluation von spezifischen Therapieverfahren in der aktuellen AWMF-Leitlinie zur Suizidalität im Kindes- und Jugendalter als unzureichend eingestuft. Ziel dieser systematischen Literaturübersicht war es, die aktuellsten Erkenntnisse zu psychotherapeutischen Verfahren bei suizidalen Kindern und Jugendlichen zusammenzutragen und kritisch zu diskutieren. Aufbauend auf anderen aktuellen systematischen Reviews wurden in die aktuelle Übersicht 11 Studien eingeschlossen, die ab dem Jahr 2013 veröffentlicht wurden. Dabei handelt es sich um Studien zu Interventionen in Notaufnahmen, zu spezifischen psychotherapeutischen Ansätzen zur Suizidalität, zu Ansätzen, die auf bestimmte Patienten- oder Risikogruppen zugeschnitten sind, und um eine Studie zu einem Online-Therapieverfahren. Erste positive Effekte lassen sich für eine familienbasierte Intervention in der Notaufnahme (hinsichtlich geringerer Hospitalisierungsraten) und für dialektisch-behaviorale, kognitiv-verhaltenstherapeutische Maßnahmen sowie familienfokussierte Verfahren (hinsichtlich der Reduktion der Suizidalität) finden. Auch eine Studie zu einer online durchgeführten Therapie konnte erste unkontrollierte, positive Effekte zeigen. Dennoch lässt sich in der Zusammenschau der Studien festhalten, dass es weiterer Evaluation von Therapieverfahren für suizidale Jugendliche bedarf. Insbesondere sind hier Replikationen der bisherigen Evaluationsergebnisse sowie die Durchführung von Studien mit größeren Stichproben sowie längeren Follow-Up-Zeitabständen vonnöten.
Brain-derived neurotrophic factor promotes VEGF-C-dependent lymphangiogenesis by suppressing miR-624-3p in human chondrosarcoma cells
Authors: Lin Chih-Yang , Wang Shih-Wei , Chen Yen-Ling , Chou Wen-Yi , Lin Ting-Yi , Chen Wei-Cheng , Yang Chen-Yu , Liu Shih-Chia , Hsieh Chia-Chu , Fong Yi-Chin , Wang Po-Chuan , Tang Chih-Hsin
Published: August 2017

Chondrosarcoma is the second most common primary malignancy of bone, and one of the most difficult bone tumors to diagnose and treat. It is well known that increased levels of vascular endothelial growth factor-C (VEGF-C) promote active tumor lymphangiogenesis and lymphatic tumor spread to regional lymph nodes. Brain-derived neurotrophic factor (BDNF) is known to promote metastasis in human chondrosarcoma cells. Knowing more about the mechanism of BDNF in VEGF-C expression and lymphangiogenesis in human chondrosarcoma would improve our understanding as how to prevent chondrosarcoma angiogenesis and metastasis, which currently lacks effective adjuvant treatment. Here, we found that BDNF expression was at least 2.5-fold higher in the highly migratory JJ012(S10) cell line as compared with the primordial cell line (JJ012). In addition, VEGF-C expression and secretion was markedly increased in JJ012(S10) cells. Conditioned medium from JJ012(S10) cells significantly promoted migration and tube formation of human lymphatic endothelial cells (LECs), whereas knockdown of BDNF attenuated LEC migration and tube formation by suppressing VEGF-C production in JJ012(S10) cells. Mechanistic investigations indicated that BDNF facilitated VEGF-C-dependent lymphangiogenesis through the MEK/ERK/mTOR signaling pathway. We also showed that microRNA (miR)-624-3p expression was negatively regulated by BDNF via the MEK/ERK/mTOR cascade. Importantly, BDNF knockdown profoundly inhibited tumor-associated lymphangiogenesis in vivo. Further analyses identified that BDNF promoted tumor lymphangiogenesis by downregulating miR-624-3p in human chondrosarcoma tissues. In conclusion, this study is the first to reveal the mechanism underlying BDNF-induced lymphangiogenesis. We suggest that BDNF may serve as a promising therapeutic target for the restriction of VEGF-C-mediated tumor lymphangiogenesis and lymphatic metastasis.
Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/AKT pathway during tacrolimus-induced oxidative stress
Authors: Lim Sun Woo , Jin Long , Luo Kang , Jin Jian , Shin Yoo Jin , Hong Sung Yi , Yang Chul Woo
Published: August 2017

Mammalian members of the forkhead box protein O (FoxO) class of transcription factors are implicated in the regulation of oxidative stress, and FoxO proteins are negatively regulated by the phosphatidylinositol 3-kinase (PI3K)–AKT signaling pathway. We examined the effect of Klotho on the PI3K/AKT pathway and manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced oxidative stress. Klotho-treated mice showed decreased Tac-induced oxidative stress accompanied by functional and histological improvements. Klotho inhibited the PI3K/AKT-mediated phosphorylation of FoxO3a and enhanced FoxO3a binding to the MnSOD promoter. Klotho increased MnSOD mRNA and protein expression in mitochondria. In addition, Klotho reduced Tac-induced mitochondrial dysfunction and decreased mitochondrial reactive oxygen species production, and these effects were enhanced by blocking PI3K activity with LY294002. Collectively, our data showed that Klotho protects Tac-induced oxidative stress by negatively regulating the PI3K/AKT pathway and subsequently enhancing FoxO3a-mediated MnSOD expression.
TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription
Authors: Gómez-Herreros Fernando , Zagnoli-Vieira Guido , Ntai Ioanna , Martínez-Macías María Isabel , Anderson Rhona M. , Herrero-Ruíz Andrés , Caldecott Keith W.
Published: August 2017

DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation ‘hotspot’, MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability.
Targeting the PI3K/Akt/mTOR signalling pathway in Cystic Fibrosis
Authors: Reilly R. , Mroz M. S. , Dempsey E. , Wynne K. , Keely S. J. , McKone E. F. , Hiebel C. , Behl C. , Coppinger J. A.
Published: August 2017

Deletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (ΔF508 CFTR) is a major cause of cystic fibrosis (CF), one of the most common inherited childhood diseases. ΔF508 CFTR is a trafficking mutant that is retained in the endoplasmic reticulum (ER) and unable to reach the plasma membrane. Efforts to enhance exit of ΔF508 CFTR from the ER and improve its trafficking are of utmost importance for the development of treatment strategies. Using protein interaction profiling and global bioinformatics analysis we revealed mammalian target of rapamycin (mTOR) signalling components to be associated with ∆F508 CFTR. Our results demonstrated upregulated mTOR activity in ΔF508 CF bronchial epithelial (CFBE41o-) cells. Inhibition of the Phosphatidylinositol 3-kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR) pathway with 6 different inhibitors demonstrated an increase in CFTR stability and expression. Mechanistically, we discovered the most effective inhibitor, MK-2206 exerted a rescue effect by restoring autophagy in ΔF508 CFBE41o- cells. We identified Bcl-2-associated athanogene 3 (BAG3), a regulator of autophagy and aggresome clearance to be a potential mechanistic target of MK-2206. These data further link the CFTR defect to autophagy deficiency and demonstrate the potential of the PI3K/Akt/mTOR pathway for therapeutic targeting in CF.
Host mechanisms involved in cattle Escherichia coli O157 shedding: a fundamental understanding for reducing foodborne pathogen in food animal production
Authors: Wang Ou , McAllister Tim A. , Plastow Graham , Stanford Kim , Selinger Brent , Guan Le Luo
Published: August 2017

The host mechanisms involved in Escherichia coli O157 super-shedding in cattle is largely unknown. In this study, the comparison of transcriptomes of intestinal tissues between super-shedders (SS) and cattle negative for E. coli O157 (NS) was performed, aiming to identify genes that are potentially associated with super-shedding. In total, 16,846 ± 639 (cecum) to 18,137 ± 696 (distal jejunum) were expressed throughout the intestine, with the expressed genes associated with immune functions more pronounced in the small intestine. In total, 351 differentially expressed (DE) genes were identified throughout the intestine between SS and NS, with 101 being up-regulated and 250 down-regulated in SS. Functional analysis revealed DE genes were involved in increased T-cell responses and cholesterol absorption in the distal jejunum and descending colon, and decreased B-cell maturation in the distal jejunum of SS. RNA-Seq based SNP discovery revealed that the mutations in seven DE genes involved in leukocyte activation and cholesterol transportation were associated with E. coli O157 shedding. Our findings suggest that T-cell responses and cholesterol metabolism in the intestinal tract may be associated with super-shedding phenomenon, and the SNPs in the DE genes are possibly associated with the observed gene expression difference between SS and NS.
High-resolution transport-of-intensity quantitative phase microscopy with annular illumination
Authors: Zuo Chao , Sun Jiasong , Li Jiaji , Zhang Jialin , Asundi Anand , Chen Qian
Published: August 2017

For quantitative phase imaging (QPI) based on transport-of-intensity equation (TIE), partially coherent illumination provides speckle-free imaging, compatibility with brightfield microscopy, and transverse resolution beyond coherent diffraction limit. Unfortunately, in a conventional microscope with circular illumination aperture, partial coherence tends to diminish the phase contrast, exacerbating the inherent noise-to-resolution tradeoff in TIE imaging, resulting in strong low-frequency artifacts and compromised imaging resolution. Here, we demonstrate how these issues can be effectively addressed by replacing the conventional circular illumination aperture with an annular one. The matched annular illumination not only strongly boosts the phase contrast for low spatial frequencies, but significantly improves the practical imaging resolution to near the incoherent diffraction limit. By incorporating high-numerical aperture (NA) illumination as well as high-NA objective, it is shown, for the first time, that TIE phase imaging can achieve a transverse resolution up to 208 nm, corresponding to an effective NA of 2.66. Time-lapse imaging of in vitro Hela cells revealing cellular morphology and subcellular dynamics during cells mitosis and apoptosis is exemplified. Given its capability for high-resolution QPI as well as the compatibility with widely available brightfield microscopy hardware, the proposed approach is expected to be adopted by the wider biology and medicine community.
TDP-43 stabilises the processing intermediates of mitochondrial transcripts
Authors: Izumikawa Keiichi , Nobe Yuko , Yoshikawa Harunori , Ishikawa Hideaki , Miura Yutaka , Nakayama Hiroshi , Nonaka Takashi , Hasegawa Masato , Egawa Naohiro , Inoue Haruhisa , Nishikawa Kouki , Yamano Koji , Simpson Richard J. , Taoka Masato , Yamauchi Yoshio , Isobe Toshiaki , Takahashi Nobuhiro
Published: August 2017

The 43-kDa trans-activating response region DNA-binding protein 43 (TDP-43) is a product of a causative gene for amyotrophic lateral sclerosis (ALS). Despite of accumulating evidence that mitochondrial dysfunction underlies the pathogenesis of TDP-43–related ALS, the roles of wild-type TDP-43 in mitochondria are unknown. Here, we show that the small TDP-43 population present in mitochondria binds directly to a subset of mitochondrial tRNAs and precursor RNA encoded in L-strand mtDNA. Upregulated expression of TDP-43 stabilised the processing intermediates of mitochondrial polycistronic transcripts and their products including the components of electron transport and 16S mt-rRNA, similar to the phenotype observed in cells deficient for mitochondrial RNase P. Conversely, TDP-43 deficiency reduced the population of processing intermediates and impaired mitochondrial function. We propose that TDP-43 has a novel role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts.
Neonatal leptin treatment reverses the bone-suppressive effects of maternal undernutrition in adult rat offspring
Authors: Firth Elwyn C. , Gamble Greg D. , Cornish Jillian , Vickers Mark H.
Published: August 2017

Alterations in the early life environment, including maternal undernutrition (UN) during pregnancy, can lead to increased risk of metabolic and cardiovascular disorders in offspring. Leptin treatment of neonates born to UN rats reverses the programmed metabolic phenotype, but the possible benefits of this treatment on bone tissue have not been defined. We describe for the first time the effects of neonatal leptin treatment on bone in adult offspring following maternal UN. Offspring from either UN or ad libitum-fed (AD) rats were treated with either saline or leptin (2.5 µg/ g.d on postnatal days (D)3–13) and were fed either a chow or high fat (HF) diet from weaning until study completion at D170. Analysis of micro-tomographic data of the left femur showed highly significant effects of UN on cortical and trabecular bone tissue indices, contributing to inferior microstructure and bone strength, almost all of which were reversed by early leptin life treatment. The HF fat diet negatively affected trabecular bone tissue, but the effects of only trabecular separation and number were reversed by leptin treatment. The negative effects of maternal UN on skeletal health in adult offspring might be prevented or attenuated by various interventions including leptin. Establishment of a minimal efficacious leptin dose warrants further study.
The trophic role of a large marine predator, the tiger shark Galeocerdo cuvier
Authors: Ferreira Luciana C. , Thums Michele , Heithaus Michael R. , Barnett Adam , Abrantes Kátya G. , Holmes Bonnie J. , Zamora Lara M. , Frisch Ashley J. , Pepperell Julian G. , Burkholder Derek , Vaudo Jeremy , Nowicki Robert , Meeuwig Jessica , Meekan Mark G.
Published: August 2017

Tiger sharks were sampled off the western (Ningaloo Reef, Shark Bay) and eastern (the Great Barrier Reef; GBR, Queensland and New South Wales; NSW) coastlines of Australia. Multiple tissues were collected from each shark to investigate the effects of location, size and sex of sharks on δ13C and δ15N stable isotopes among these locations. Isotopic composition of sharks sampled in reef and seagrass habitats (Shark Bay, GBR) reflected seagrass-based food-webs, whereas at Ningaloo Reef analysis revealed a dietary transition between pelagic and seagrass food-webs. In temperate habitats off southern Queensland and NSW coasts, shark diets relied on pelagic food-webs. Tiger sharks occupied roles at the top of food-webs at Shark Bay and on the GBR, but not at Ningaloo Reef or off the coast of NSW. Composition of δ13C in tissues was influenced by body size and sex of sharks, in addition to residency and diet stability. This variability in stable isotopic composition of tissues is likely to be a result of adaptive foraging strategies that allow these sharks to exploit multiple shelf and offshore habitats. The trophic role of tiger sharks is therefore both context- and habitat-dependent, consistent with a generalist, opportunistic diet at the population level.
Information Security Scheme Based on Computational Temporal Ghost Imaging
Authors: Jiang Shan , Wang Yurong , Long Tao , Meng Xiangfeng , Yang Xiulun , Shu Rong , Sun Baoqing
Published: August 2017

An information security scheme based on computational temporal ghost imaging is proposed. A sequence of independent 2D random binary patterns are used as encryption key to multiply with the 1D data stream. The cipher text is obtained by summing the weighted encryption key. The decryption process can be realized by correlation measurement between the encrypted information and the encryption key. Due to the instinct high-level randomness of the key, the security of this method is greatly guaranteed. The feasibility of this method and robustness against both occlusion and additional noise attacks are discussed with simulation, respectively.