bluuebunny/crossref_metadata_2025 huggingface dataset:
An individual patient data meta‐analysis on factors associated with adverse drug events in surgical and non‐surgical inpatients
Authors: Boeker Eveline B. , Ram Kim , Klopotowska Joanna E. , de Boer Monica , Creus Montse Tuset , de Andrés Ana L. , Sakuma Mio , Morimoto Takeshi , Boermeester Marja A. , Dijkgraaf Marcel G. W.
Published: September 2014

Aim

The incidence of adverse drug events (ADEs) in surgical and non‐surgical patients may differ. This individual patient data meta‐analysis (IPDMA) identifies patient characteristics and types of medication most associated with patients experiencing ADEs and suggests target areas for reducing harm and implementing focused interventions.

Methods

Authors of eligible studies on preventable ADEs (pADEs) were approached for collaboration. For assessment of differences among (non‐)surgical patients and identification of associated factors descriptive statistics, Pearson chi‐square, Poisson and logistic regression analyses were performed. For identification of high risk drugs (HRDs), a model was developed based on frequency, severity and preventability of medication related to ADEs.

Results

Included were 5367 patients from four studies. Patients aged ≥ 77 years experienced more ADEs and pADEs compared with patients aged ≤ 52 years (odds ratios (OR) 2.12 (95% CI 1.70, 2.65) and 2.55 (95% CI 1.70, 3.84), respectively, both P < 0.05). Polypharmacy on admission also increased the risk of ADEs (OR 1.21 (95% CI 1.03, 1.44), P < 0.05) and pADEs (OR 1.85 (95% CI 1.34, 2.56), P < 0.05). pADEs were associated with more severe harm than non‐preventable ADEs (54% vs. 32%, P < 0.05). The top five HRDs were antibiotics, sedatives, anticoagulants, diuretics and antihypertensives. Events associated with HRDs included diarrhoea or constipation, abnormal liver function test and central nervous system events. Most pADEs resulted from prescribing errors (90%).

Conclusion

Elderly patients with polypharmacy on admission and receiving antibiotics, sedatives, anticoagulants, diuretics or antihypertensives were more prone to experiencing ADEs. Efficiency in prevention of ADEs may be improved by targeted vigilance systems for alertness of physicians and pharmacists.
Evaluation of graft stiffness using acoustic radiation force impulse imaging after living donor liver transplantation
Authors: Ijichi Hideki , Shirabe Ken , Matsumoto Yoshihiro , Yoshizumi Tomoharu , Ikegami Toru , Kayashima Hiroto , Morita Kazutoyo , Toshima Takeo , Mano Yohei , Maehara Yoshihiko
Published: September 2014

Acoustic radiation force impulse (ARFI) imaging is an ultrasound‐based modality to evaluate tissue stiffness using short‐duration acoustic pulses in the region of interest. Virtual touch tissue quantification (VTTQ), which is an implementation of ARFI, allows quantitative assessment of tissue stiffness. Twenty recipients who underwent living donor liver transplantation (LDLT) for chronic liver diseases were enrolled. Graft types included left lobes with the middle hepatic vein and caudate lobes (n = 11), right lobes (n = 7), and right posterior segments (n = 2). They underwent measurement of graft VTTQ during the early post‐LDLT period. The VTTQ value level rose after LDLT, reaching a maximum level on postoperative day 4. There were no significant differences in the VTTQ values between the left and right lobe graft types. Significant correlations were observed between the postoperative maximum value of VTTQ and graft volume‐to‐recipient standard liver volume ratio, portal venous flow to graft volume ratio, and post‐LDLT portal venous pressure. The postoperative maximum serum alanine aminotransferase level and ascites fluid production were also significantly correlated with VTTQ. ARFI may be a useful diagnostic tool for the noninvasive and quantitative evaluation of the severity of graft dysfunction after LDLT.
Utility of pre‐procurement bedside liver biopsy in the deceased extended‐criteria liver donor
Authors: Mangus Richard S. , Borup Tim C. , Popa Sam , Saxena Romil , Cummings Oscar , Tector A. Joseph
Published: September 2014

Introduction

The Indiana Organ Procurement Organization (IOPO) utilizes preoperative bedside liver biopsies in certain extended‐criteria donors (ECDs), obtained by the on‐site coordinator, to determine the utility of pursuing donation. This study reports the clinical and financial outcomes for this management strategy.

Methods

All bedside liver biopsies obtained in ECDs over a five‐yr period were reviewed. Study variables included the following: indication for biopsy, biopsy results, taking the case to the operating room, transplantation of the donor liver, and graft survival. All biopsies were processed at a single university center.

Results

There were 110 donors biopsied. Primary indications included the following: old age (29%), extensive/current alcohol abuse (26%), hepatitis C‐positive serology (21%), obesity (25%), and severely elevated liver function enzymes (18%). Biopsy results demonstrated a potentially transplantable liver in 73 cases (66%), all of whom were taken to the OR (while 37 ruled out for donation based upon liver biopsy [34%]). Of all biopsied livers, 49 ultimately were transplanted (45%). Intra‐operative decisions included the following: transplant 51/73 (70%), surgeon decision to exclude 20/73 (27%), nonuse due to finding of malignancy two (3%).

Conclusions

Bedside liver biopsy may be a valuable tool to determine the utility in pursuing donation in ECDs, particularly with liver‐only donors.
Jesus' Prophethood and Islam: Insights from the Risale‐i Nur
Authors: Largen Kristin Johnston
Published: September 2014

While Jesus’ prophethood is an indisputable component of his identity in the Christian tradition, it has been marginalized for centuries in favor of his identity as savior. In this article, I argue that an engagement with an understanding of Jesus’ prophethood in Islam, particularly as explicated by the Turkish thinker Bediüzzaman Said Nursi, can help Christians recover a more robust interpretation of Jesus as prophet that has a positive impact on a Christian articulation of the church and of discipleship today.
Beyond Deep Incarnation: Rethinking Christology in Radical Lutheran Terms
Authors: Peterson Daniel J.
Published: September 2014

This article takes the demise of Christendom and what Diana Butler Bass calls the end of religion as its point of departure for a “radical” rethinking of God in fully kenotic terms. It rejects any vestige of otherworldly transcendence as a temptation to escapism, inviting us instead to seek God's complete presence among us here in the world. Going beyond Niels Gregersen's understanding of the deep incarnation of the Logos and starting instead with a complete commitment to the infra‐Lutheranum, the author presents a radical Lutheran theology that embraces a total kenosis of God whose liberating and life‐giving reappearance we must find implicit among us in unexpected places, not least of which might include the embers of a dying church or the crumbling of our religious institutions.
Hospice Care and a Theology for Patients at the End of Life
Authors: Tracy Tara Flanagan
Published: September 2014

In Richard Kearney's text Anatheism, he claims that one can respond to the call of the stranger in two ways, with hospitality or with hostility. However, because the stranger possibly bears the presence of the divine, he urges one to risk responding to the stranger's call with hospitality rather than hostility, opening oneself up to encountering the sacred in the form of the stranger. In the present analysis, I claim that hospitality toward the stranger is modeled in the hospice philosophy of care for dying patients. I note the distinctions between the biomedical model of health care and the biopsychosoical model of care, and draw on Kearney's framework and Dorothee Soelle's text Suffering to suggest that, with regard to how to interpret pain, the act of hosting can be an option more viable than that of demonstrating hospitality.
Brain glucose sensing, glucokinase and neural control of metabolism and islet function
Authors: Ogunnowo‐Bada E. O. , Heeley N. , Brochard L. , Evans M. L.
Published: September 2014

It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin‐stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel – emergency counter‐regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low‐affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases.
Gut microbiota, nutrient sensing and energy balance
Authors: Duca F. A. , Lam T. K. T.
Published: September 2014

The gastrointestinal (GI) tract is a highly specialized sensory organ that provides crucial negative feedback during a meal, partly via a gut–brain axis. More specifically, enteroendocrine cells located throughout the GI tract are able to sense and respond to specific nutrients, releasing gut peptides that act in a paracrine, autocrine or endocrine fashion to regulate energy balance, thus controlling both food intake and possibly energy expenditure. Furthermore, the gut microbiota has been shown to provide a substantial metabolic and physiological contribution to the host, and metabolic disease such as obesity has been associated with aberrant gut microbiota and microbiome. Interestingly, recent evidence suggests that the gut microbiota can impact the gut–brain axis controlling energy balance, at both the level of intestinal nutrient‐sensing mechanisms, as well as potentially at the sites of integration in the central nervous system. A better understanding of the intricate relationship between the gut microbiota and host energy‐regulating pathways is crucial for uncovering the mechanisms responsible for the development of metabolic diseases and for possible therapeutic strategies.
Cooperation between cAMP signalling and sulfonylurea in insulin secretion
Authors: Shibasaki T. , Takahashi T. , Takahashi H. , Seino S.
Published: September 2014

Although glucose is physiologically the most important regulator of insulin secretion, glucose‐induced insulin secretion is modulated by hormonal and neural inputs to pancreatic β‐cells. Most of the hormones and neurotransmitters evoke intracellular signals such as cAMP, Ca2+, and phospholipid‐derived molecules by activating G protein‐coupled receptors (GPCRs). In particular, cAMP is a key second messenger that amplifies insulin secretion in a glucose concentration‐dependent manner. The action of cAMP on insulin secretion is mediated by both protein kinase A (PKA)‐dependent and Epac2A‐dependent mechanisms. Many of the proteins expressed in β‐cells are phosphorylated by PKA in vitro, but only a few proteins in which PKA phosphorylation directly affects insulin secretion have been identified. On the other hand, Epac2A activates the Ras‐like small G protein Rap in a cAMP‐dependent manner. Epac2A is also directly activated by various sulfonylureas, except for gliclazide. 8‐pCPT‐2′‐O‐Me‐cAMP, an Epac‐selective cAMP analogue, and glibenclamide, a sulfonylurea, synergistically activate Epac2A and Rap1, whereas adrenaline, which suppresses cAMP production in pancreatic β‐cells, blocks activation of Epac2A and Rap1 by glibenclamide. Thus, cAMP signalling and sulfonylurea cooperatively activate Epac2A and Rap1. This interaction could account, at least in part, for the synergistic effects of incretin‐related drugs and sulfonylureas in insulin secretion. Accordingly, clarification of the mechanism of Epac2A activation may provide therapeutic strategies to improve insulin secretion in diabetes.
Factors Impacting the Mental Health of the Caregivers of Children with Asthma in China: Effects of Family Socioeconomic Status, Symptoms Control, Proneness to Shame, and Family Functioning
Authors: Zhou Ting , Yi Chunli , Zhang Xuxia , Wang Yuyin
Published: September 2014

Caregiver mental health is widely considered to be an important factor influencing children's asthma symptoms. The present study aimed to examine key factors that contribute to caregiver mental health in pediatric asthma with a Chinese sample. Two hundred participants reported their family socioeconomic status (SES), proneness to shame, asthma symptoms control of their child, family functioning, and their depression and anxiety symptoms. Results suggested that low family SES, low family functioning, and a high level of shame proneness were associated with high levels of anxiety and depression for caregivers. Family functioning mediated the effects of SES and shame on caregiver mental health and also moderated the effects of SES and shame on caregiver depression. This study highlights the importance of reducing experience of shame and enhancing family functioning in families affected by pediatric asthma.
Signal transducer and activator of transcription 3 and the phosphatidylinositol 3‐kinase regulatory subunits p55α and p50α regulate autophagy in vivo
Authors: Pensa Sara , Lloyd‐Lewis Bethan , Sargeant Timothy J. , Resemann Henrike K. , Kahn C. Ronald , Watson Christine J.
Published: September 2014

Mammary gland involution involves a process that includes one of the most dramatic examples of cell death in an adult mammalian organism. We have previously shown that signal transducer and activator of transcription 3 (Stat3) regulates a lysosomal pathway of cell death in the first 48 h of involution and induces lysosome leakiness in mammary epithelial cells. Interestingly, Stat3 is associated also with the striking induction of autophagy that occurs concomitantly with cell death, presumably as a transient survival mechanism. The phosphatidylinositol 3‐kinase regulatory subunits p55α and p50α are dramatically and specifically upregulated at the transcriptional level by Stat3 at the onset of involution. We show here that ablation of either Stat3 or p55α/p50α in vivo affects autophagy during involution. We used two different cell culture models (normal mammary epithelial cells and mouse embryonic fibroblasts) to further investigate the role of p55α/p50α in autophagy regulation. Our results demonstrate a direct role for p55α/p50α as inhibitors of autophagy mediated by p85α. Thus, Stat3 and its downstream targets p55α/p50α are key regulators of the balance between autophagy and cell death in vivo.
Epstein–Barr virus encoded microRNAs target SUMO‐regulated cellular functions
Authors: Callegari Simone , Gastaldello Stefano , Faridani Omid R. , Masucci Maria G.
Published: September 2014

Post‐translational modification by the small ubiquitin‐like modifier (SUMO) regulates the cellular response to different types of stress and plays a pivotal role in the control of oncogenic viral infections. Here we investigated the capacity of microRNAs (miRNAs) encoded by Epstein–Barr virus to interfere with the SUMO signaling network. Using a computational strategy that scores different properties of miRNA–mRNA target pairs, we identified a minimal set of 575 members of the SUMO interactome that may be targeted by one or more Epstein–Barr virus miRNAs. A significant proportion of the candidates cluster in a functional network that controls chromatin organization, stress, DNA damage and immune responses, apoptosis and transforming growth factor beta signaling. Multiple components of the transforming growth factor beta signaling pathway were inhibited upon upregulation of the BamHI‐H rightward open reading frame 1 (BHRF1) encoded miRNAs in cells transduced with recombinant lentiviruses or entering the productive virus cycle. These findings point to the capacity of viral miRNAs to interfere with SUMO‐regulated cellular functions that control key aspects of viral replication and pathogenesis.
Control of periphyton standing crop in an Atlantic Forest stream: the relative roles of nutrients, grazers and predators
Authors: Lourenço‐Amorim Christine , Neres‐Lima Vinicius , Moulton Timothy Peter , Sasada‐Sato Cristiano Yuji , Oliveira‐Cunha Priscila , Zandonà Eugenia
Published: September 2014

Periphytic algae are an important source of energy fuelling stream food webs. Periphytic algal biomass can be controlled by bottom‐up and top‐down forces, but there are few studies that have investigated these effects simultaneously, especially in tropical streams, where periphyton can be a very important carbon source. Here, we investigated the bottom‐up effects of nutrients and the top‐down effects of grazers and predators in a coastal tropical stream in Brazil.

We employed nutrient‐diffusing substrata to test for nutrient limitation, placed inside electric exclosures of different intensities, which prevented consumers from entering the electrified area. We used four types of substrata: one enriched with nitrogen alone (N), one with phosphorus alone (P), one with nitrogen + phosphorus (NP) and one control with no nutrients added (C). The electric exclosure had three treatments: high electricity that excluded both predators (Macrobrachium olfersi shrimps) and grazers (Baetidae mayflies), low electricity that excluded only shrimps, and a control treatment with no electricity where both shrimps and mayflies were allowed to enter.

The limiting nutrient in the stream was nitrogen. Our results showed a greater magnitude of bottom‐up effects, with periphytic algae responding more strongly to nutrient addition than to grazers or predators. Top‐down control was not as strong, but periphytic algae responded negatively to grazers, especially in the absence of predators. This suggests that shrimps, either directly or indirectly, inhibit mayfly grazing activity. The response of periphytic algae to nutrients was stronger in the absence of grazers. Thus, top‐down effects, both directly and indirectly through a trophic cascade, can dampen the response to nitrogen addition, diminishing the degree of resource limitation.
Ten years of vegetation assembly after a North American mega fire
Authors: Abella Scott R. , Fornwalt Paula J.
Published: September 2014

Altered fuels and climate change are transforming fire regimes in many of Earth's biomes. Postfire reassembly of vegetation – paramount to C storage and biodiversity conservation – frequently remains unpredictable and complicated by rapid global change. Using a unique data set of pre and long‐term postfire data, combined with long‐term data from nearby unburned areas, we examined 10 years of understory vegetation assembly after the 2002 Hayman Fire. This fire was the largest wildfire in recorded history in Colorado,USA. Resistance (initial postfire deviance from prefire condition) and resilience (return to prefire condition) declined with increasing fire severity. However, via both resistance and resilience, ‘legacy’ species of the prefire community constituted >75% of total plant cover within 3 years even in severely burned areas. Perseverance of legacy species, coupled with new colonizers, created a persistent increase in community species richness and cover over prefire levels. This was driven by a first‐year increase (maintained over time) in forbs with short life spans; a 2–3‐year delayed surge in long‐lived forbs; and a consistent increase in graminoids through the 10th postfire year. Burning increased exotic plant invasion relative to prefire and unburned areas, but burned communities always were >89% native. This study informs debate in the literature regarding whether these increasingly large fires are ‘ecological catastrophes.’ Landscape‐scale severe burning was catastrophic from a tree overstory perspective, but from an understory perspective, burning promoted rich and productive native understories, despite the entire 10‐year postfire period receiving below‐average precipitation.
Transient expression of RAD51 in the late G2‐phase is required for cell cycle progression in synchronous Physarum cells
Authors: Le Cigne Anthony , Menil‐Philippot Vanessa , Fleury Fabrice , Takahashi Masayuki , Thiriet Christophe
Published: September 2014

The homologous recombination factor RAD51 is highly conserved. This criterion enabled us to identify a RAD51 ortholog in Physarum polycephalum. We found that the Physarum protein presents a high homology to the human protein and cross‐reacted with antibodies directed against the human RAD51. Taking advantage of the natural synchrony of millions of nuclei within a single cell of Physarum, we investigated the fluctuation of the amount of the PpRAD51 throughout the cell cycle. Our results showed that in the late G2‐phase, RAD51 was transiently expressed in a large quantity. Furthermore, knocking‐down RAD51 in the G2‐phase abolished this transient expression before mitosis and affected cell cycle progression. These results support the idea that RAD51 plays a role in the progression of the cell cycle in the late G2‐phase.
Fine Tuning of 3D LTCC Inductor Properties Using Combination of Different Ferrite and Dielectric Tapes
Authors: Marić Andrea , Blaž Nelu , Živanov Ljiljana , Radosavljević Goran
Published: September 2014

Presented research offers solutions for properties alternation of 3D LTCC inductors by variation of materials implemented for their fabrication. Investigated geometry is solenoid‐shape micro‐inductor. Two types of dielectric cores are applied to achieve increase of quality factor for over 40% at GHz range. Five different stacks of ferrite material combinations are implemented when either fine inductance adjustments are needed or in cases when higher quality factor is required at MHz range frequencies. Increase of starting inductance of solid dielectric core solenoid is realized in tuning range of (35–60) %. Different ferrite core configurations can double quality factor maximum.
Severe cardiomyopathy revealing antineutrophil cytoplasmic antibodies‐negative eosinophilic granulomatosis with polyangiitis
Authors: Bouiller K. , Samson M. , Eicher J.‐C. , Audia S. , Berthier S. , Leguy V. , Humbert O. , Martin L. , Lorgis L. , Cottin Y. , Bonnotte B. , Lorcerie B.
Published: September 2014

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of systemic vasculitis in which cardiac involvement is frequent and severe, and accounts for half of EGPA‐related deaths. ANCA‐positive EGPA differs from ANCA‐negative EGPA in that the former is significantly associated with renal involvement, peripheral neuropathy and biopsy proven vasculitis, whereas the latter is associated with cardiac involvement. Herein, we report a case of EGPA with myocarditis in a woman, who was successfully treated with steroids and cyclophosphamide. This report highlights the importance of diagnosing cardiac involvement in EGPA early, especially in ANCA‐negative patients.
Rapid rule out of myocardial infarction with the use of copeptin as a biomarker for cardiac injury
Authors: Jayasinghe R. , Narasimhan S. , Tran T. H. , Paskaranandavadivel A.
Published: September 2014

Copeptin is a non‐specific marker of an endogenous stress response. A dual biomarker marker approach involving the simultaneous use of troponin and copeptin assays may assist early exclusion of acute coronary syndrome in Australian emergency departments. The utility and limitations of this approach are discussed.
Prospective Surgical Site Infection Surveillance in Dogs
Authors: Turk Ryen , Singh Ameet , Weese J. Scott
Published: September 2014

Objective

To 1) describe the incidence of surgical site infections (SSI) in dogs undergoing surgery at the Ontario Veterinary College Health Sciences Centre; 2) describe and compare procedure‐specific SSI rates; and 3) identify factors associated with development of SSI.

Study Design

Prospective, cohort study

Animals

Dogs (n = 846) undergoing surgery during 45 weeks (September 2010–July 2011).

Methods

Follow‐up telephone conversation with dog owners was performed 30 days postoperatively, with additional 1‐year follow‐up performed for cases with surgical implants. A standardized questionnaire was administered to detect and characterize SSI.

Results

SSI were identified in 26 (3.0%) dogs; 11 (42%) were classified as superficial SSI, whereas 13 were deep, and 2 were organ/space. Of the confirmed SSI, only 17 (65%) were documented in the medical records. Hypotension (P = .011), class of surgery (P = .029), and use of an implant (P = .001) increased the risk of SSI. Microbial cultures were submitted for 19 cases (73%) and of those, 74% were staphylococci.

Conclusions

SSI can result in devastating consequences in dogs and understanding risk factors is critical to target prevention practices. Whereas some risk factors such as hypotension are modifiable, others such as class of surgery are not. When possible, active surveillance should be used as part of a hospital infection control program.
Perioperative Administration of Antimicrobials During Tibial Plateau Leveling Osteotomy
Authors: Nazarali Alim , Singh Ameet , Weese J. Scott
Published: September 2014

Objective

To evaluate perioperative antimicrobial administration during tibial plateau leveling osteotomy (TPLO) in dogs at the Ontario Veterinary College Health Sciences Centre.

Study Design

Retrospective case series.

Animals

Dogs (n = 184) that had TPLO (n = 226).

Methods

Medical records were reviewed and data collected included timing and dosage of pre, intra, and postoperative antimicrobial administration, method of stifle inspection, duration of surgery, duration of anesthesia, development of surgical site infection (SSI), microbiological investigation, implant removal, and possible comorbidities. Univariable analysis was conducted, followed by stepwise forward logistic regression to determine factors associated with SSI.

Results

Of the 225 cases administered perioperative antimicrobials, 96 (42.5%) received appropriate perioperative antimicrobial prophylaxis based on target times for preoperative and intraoperative dosing. Postoperative antimicrobials were administered to 54 (23.9%) of cases. Surgical site infection was documented in 30 (13.3%) cases.Staphylococcus pseudintermediuswas isolated from 15/17 (88.2%) SSI from which a bacterium was isolated, with 6/15 (40%) being methicillin‐resistantStaphylococcus pseudintermedius(MRSP). Postoperative administration of antimicrobials was protective for SSI (OR 0.1367;P = .0001; 95% CI = 0.021, 0.50). Duration of anesthesia time was associated with the likelihood of development of SSI (OR = 1.0094;P = .001; 95% CI = 1.00, 1.02).

Conclusion

Current practices for administration of antimicrobial prophylaxis during TPLO can be improved. There was no association between timing of antibiotic administration that was inconsistent with the target and development of SSI. Further study into risk factors of TPLO SSI is required.
Effect of Angiotensin Converting Enzyme Inhibitors on Soluble Tumor‐Necrosis‐Factor‐Related Apoptosis‐Inducing Ligand Levels – Association With Neointimal Hyperplasia in Drug Eluting Stents
Authors: GIANNOPOULOS GEORGIOS , PANAGOPOULOU VASILIKI , DEFTEREOS SPYRIDON , ANGELIDIS CHRISTOS , DAVLOUROS PERIKLIS , SYNETOS ANDREAS , TOUTOUZAS KONSTANTINOS , ALEXOPOULOS DIMITRIOS , CLEMAN MICHAEL W. , TOUSOULIS DIMITRIOS
Published: September 2014

Objective

To test the hypothesis that angiotensin converting enzyme inhibitors (ACEi) affect soluble tumor‐necrosis‐factor‐related apoptosis‐inducing ligand (sTRAIL) and this interaction is associated with less in‐drug‐eluting‐stent (DES) neointimal hyperplasia following percutaneous coronary intervention (PCI).

Methods

From our database of patients with elective PCI and baseline intravascular ultrasound (IVUS) evaluation of the implanted DES, we randomly selected 60 patients who were prescribed an ACEi and 60 matched controls, who did not receive an ACEi following PCI. All patients underwent coronary angiography and IVUS. sTRAIL was measured in samples from the stented coronary artery and a peripheral vein.

Results

sTRAIL concentration was higher in the ACEi group, both in coronary and peripheral samples: 104 [78–139] pg/ml versus 63 [45–100] pg/ml (P < 0.001) and 99 [73–135] pg/ml versus 69 [49–103] pg/ml (P = 0.002), respectively. There was an inverse association (standardized beta −0.760; P < 0.001) between sTRAIL and lumen area loss in both treatment groups. In the multivariable analysis, log(sTRAIL) was an independent negative predictor of lumen area loss (standardized beta −0.660, adjusted 95% confidence interval −0.722 to −0.466).

Conclusions

Treatment with ACEi was associated with higher sTRAIL levels and lower lumen area loss in the IVUS evaluation of implanted DES. sTRAIL levels were negatively associated with in‐stent neointima hyperplasia in these postPCI patients.
Brain‐derived neurotrophic factor prevents the endothelial barrier dysfunction induced by interleukin‐1β and tumor necrosis factor‐α
Authors: Matsuda S. , Fujita T. , Kajiya M. , Kashiwai K. , Takeda K. , Shiba H. , Kurihara H.
Published: September 2014

Background and Objective

Brain‐derived neurotrophic factor (BDNF) promotes the regeneration of periodontal tissue. Although a local inflammatory step is required to initiate the subsequent process of tissue regeneration, excessive inflammation may inhibit or delay tissue regeneration. Therefore, the regulation of inflammation is essential for periodontal tissue regeneration. In the present study, we examined the influence of BDNF on the human microvascular endothelial cell (HMVEC) barrier dysfunction induced by interleukin (IL)‐1β or tumor necrosis factor (TNF)‐α to determine the effects of BDNF on the regulation of local inflammation in periodontal tissue regeneration.

Material and Methods

Endothelial permeability was analyzed using a Dextran transport assay with transwell plates. The expression of vascular endothelial (VE)‐cadherin was assessed by immunoblotting and immunofluorescence microscopy.

Results

BDNF (25 ng/mL) inhibited increase induced in endothelial permeability by IL‐1β and TNF‐α. IL‐1β and TNF‐α decreased VE‐cadherin protein levels, while BDNF recovered the reduction in HMVECs. BDNF protected the increase induced in endothelial permeability by IL‐1β and TNF‐α through TrkB. The single addition of BDNF into the culture increased the expression of VE‐cadherin in HMVECs.

Conclusion

BDNF played an important role in inhibiting endothelial barrier dysfunction, which suggests that it may assist in enhancing periodontal tissue regeneration.
Identification of transactivation‐responsive DNA‐binding protein 43 (TARDBP43; TDP‐43) as a novel factor for TNF‐α expression upon lipopolysaccharide stimulation in human monocytes
Authors: Murata H. , Hattori T. , Maeda H. , Takashiba S. , Takigawa M. , Kido J. , Nagata T.
Published: September 2014

Background and Objective

Tumor necrosis factor alpha (TNF‐α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF‐α gene regulation is not well elucidated. We previously identified a novel region located from −550 to −487 in human TNF‐α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF‐κB) but showed lipopolysaccharide (LPS)‐induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF‐α expression.

Material and Methods

To identify DNA‐binding proteins that bound to the target region of TNF‐α promoter, a cDNA library from LPS‐stimulated human monocytic cell line THP‐1 was screened using a yeast one‐hybrid system. Cellular localizations of the DNA‐binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS‐stimulated THP‐1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real‐time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA‐binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF‐α expression.

Results

Several candidates were identified from the cDNA library and transactivation‐responsive DNA‐binding protein 43 (TARDBP43; TDP‐43) was focused on. Western blot analysis revealed that nuclear TDP‐43 protein was increased in the LPS‐stimulated THP‐1 cells. Expression of TDP‐43 mRNA was already enhanced before TNF‐α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG‐tagged TDP‐43 bound to the −550 to −487 TNF‐α promoter fragments. Overexpression of TDP‐43 in THP‐1 cells resulted in an increase of TNF‐α expression. Knockdown of TDP‐43 in THP‐1 cells downregulated TNF‐α expression.

Conclusion

We identified TDP‐43 as one of the novel TNF‐α factors and found that it bound to the LPS‐responsive element in the TNF‐α promoter to increase TNF‐α expression.
Calving location selection patterns of saiga antelope in Mongolia
Authors: Buuveibaatar B. , Fuller T. K. , Young J. K. , Berger J.
Published: September 2014

Habitat selection for calving by ungulates is an important behavioral trait because it affects neonate survival. Generally, ungulate calving site selection varies by vulnerability to predators, local topography, habitat quality and level of human disturbance. The Mongolian saiga (Saiga tatarica mongolica) is endemic to Mongolia where a threatened population of ∼7000 exists in the northern Gobi Desert. We analyzed factors that could affect selection of saiga calving locations in the Sharga Nature Reserve, western Mongolia, using data obtained from ground surveys over 4 years between 2008 and 2012. Multiple factors explain calving location selection by saiga antelopes, based on the results of a generalized linear mixed model within a use availability framework. Individual saiga females preferred calving locations that were away from settlements and closer to water sources and avoided steeper slopes in comparison with random locations. These results demonstrate that the choice of calving locations for saiga antelope is driven by both internal and external factors. Understanding which factors influence calving location selection for saiga provides insights to protect important habitats.
Circulating mannan‐binding lectin, M‐, L‐, H‐ficolin and collectin‐liver‐1 levels in patients with acute liver failure
Authors: Laursen Tea L. , Sandahl Thomas D. , Støy Sidsel , Schiødt Frank V. , Lee William M. , Vilstrup Hendrik , Thiel Steffen , Grønbæk Henning ,   US Acute Liver Failure Study Group
Published: September 2014

Background & Aims

The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan‐binding lectin (MBL), M‐, L‐, and H‐ficolin and collectin‐liver‐1 (CL‐L1), which are predominantly synthesized in the liver. We aimed to study lectin levels in ALF patients and associations with clinical outcome.

Methods

Serum samples from 75 patients enrolled by the US ALF Study Group were collected on days 1 and 3. We included 75 healthy blood donors and 20 cirrhosis patients as controls. Analyses were performed using sandwich‐type immunoassays (ELISA, TRIFMA).

Results

At day 1, the MBL level in ALF patients was 40% lower compared with healthy controls {[median (interquartile range) 0.72 μg/ml(0.91) vs. 1.15 (1.92)(P = 0.02]}, and increased significantly by day 3 [0.83 μg/ml(0.94)(P = 0.01)]. The M‐ficolin level was 60% lower [0.54 μg/ml(0.50) vs. 1.48(1.01)(P < 0.0001)]. The CL‐L1 level at day 1 was slightly higher compared with healthy controls [3.20 μg/ml(2.37) vs. 2.64(0.72)(P = 0.11)]; this was significant at day 3 [3.35(1.84)(P = 0.006)]. H‐ and L‐ficolin levels were similar to healthy controls. Spontaneous ALF survivors had higher levels of MBL at day 1 [0.96 μg/ml(1.15) vs. 0.60(0.60)(P = 0.02)] and lower levels of L‐ficolin by day 3 compared with patients who died or were transplanted [1.61 μg/ml(1.19) vs. 2.17(2.19)(P = 0.02)].

Conclusion

We observed significant dynamics in lectin levels in ALF patients, which may suggest they play a role in ALF pathogenesis. High MBL and low L‐ficolin levels are associated with survival.
A hyperparasite affects the population dynamics of a wild plant pathogen
Authors: Tollenaere C. , Pernechele B. , Mäkinen H. S. , Parratt S. R. , Németh M. Z. , Kovács G. M. , Kiss L. , Tack A. J. M. , Laine A.‐L.
Published: September 2014

Assessing the impact of natural enemies of plant and animal pathogens on their host's population dynamics is needed to determine the role of hyperparasites in affecting disease dynamics, and their potential for use in efficient control strategies of pathogens. Here, we focus on the long‐term study describing metapopulation dynamics of an obligate pathogen, the powdery mildew (Podosphaera plantaginis) naturally infecting its wild host plant (Plantago lanceolata) in the fragmented landscape of theÅland archipelago (southwestFinland). Regionally, the pathogen persists through a balance of extinctions and colonizations, yet factors affecting extinction rates remain poorly understood. Mycoparasites of the genusAmpelomycesappear as good candidates for testing the role of a hyperparasite, i.e. a parasite of other parasites, in the regulation of their fungal hosts' population dynamics. For this purpose, we first designed a quantitativePCRassay for detection ofAmpelomycesspp. in field‐collected samples. This newly developed molecular test was then applied to a large‐scale sampling within theÅland archipelago, revealing thatAmpelomycesis a widespread hyperparasite in this system, with high variability in prevalence among populations. We found that the hyperparasite was more common on leaves where multiple powdery mildew strains coexist, a pattern that may be attributed to differential exposure. Moreover, the prevalence ofAmpelomycesat the plant level negatively affected the overwinter survival of its fungal host. We conclude that this hyperparasite may likely impact on its host population dynamics and argue for increased focus on the role of hyperparasites in disease dynamics.
TSE strain differentiation in mice by immunohistochemical PrPSc profiles and triplex Western blot
Authors: van Keulen Lucien J. M. , Langeveld Jan P. M. , Dolstra Corry H. , Jacobs Jorg , Bossers Alex , van Zijderveld Fred G.
Published: September 2014

TSE strains are routinely identified by their incubation period and vacuolation profile in the brain after intracerebral inoculation and serial passaging in inbred mouse lines. There are some major drawbacks to this method that are related to the variation in vacuolation that exists in the brains of mice infected with the same TSE strain and to variation between observers and laboratories in scoring vacuolation and determining the final incubation period.

Aim

We investigated the potential of PrPSc immunohistochemistry and triplex Western blotting as possible alternative methods to differentiate between TSE strains.

Methods

TSE reference strains ME7, 87A/87V, 22A/22C, 79A/79V and 301C/301V were intracerebrally inoculated in RIII or VM inbred mice that differ in their PrP genotype. Immunohistochemical PrPSc profiles were drawn up by scanning light microscopy both on coronal and sagittal sections.

Results

On the basis of the localization of PrPSc in the cerebral cortex, hippocampus, and cerebellar cortex and the overall type of PrPSc staining, all TSE strains could be well differentiated from each other through their typical strain dependent characteristics. In addition, Western blot showed that the combination of glycosylation profile and 12B2 epitope content of PrPSc allowed to distinguish between all reference strains except for ME7 and 22A in VM mice.

Conclusion

TSE strains in mice can be identified on the basis of their PrPSc profile alone. The potential to identify TSE strains in ruminants with these PrPSc profiles after a single primary passage in mice will be the topic of future studies.
Low intensity ultrasound inhibits brain oedema formation in rats: potential action on AQP4 membrane localization
Authors: Karmacharya Mrigendra Bir , Kim Kil Hwan , Kim See Yoon , Chung Joonho , Min Byoung‐Hyun , Park So Ra , Choi Byung Hyune
Published: September 2014

Aims

Brain oedema is a major contributing factor to the morbidity and mortality of a variety of brain disorders. Although there has been considerable progress in our understanding of pathophysiological and molecular mechanisms associated with brain oedema so far, more effective treatment is required and is still awaited. Here we intended to study the effects of low intensity ultrasound (LIUS) on brain oedema.

Methods

We prepared the rat hippocampal slice in vitro and acute water intoxication in vivo models of brain oedema. We applied LIUS stimulation in these models and studied the molecular mechanisms of LIUS action on brain oedema.

Results

We found that LIUS stimulation markedly inhibited the oedema formation in both of these models. LIUS stimulation significantly reduced brain water content and intracranial pressure resulting in increased survival of the rats. Here, we showed that the AQP4 localization was increased in the astrocytic foot processes in the oedematous hippocampal slices, while it was significantly reduced in the LIUS‐stimulated hippocampal slices. In the in vivo model too, AQP4 expression was markedly increased in the microvessels of the cerebral cortex and hippocampus after water intoxication but was reduced in the LIUS‐stimulated rats.

Conclusions

These data show that LIUS has an inhibitory effect on cytotoxic brain oedema and suggest its therapeutic potential to treat brain oedema. We propose that LIUS reduces the AQP4 localization around the astrocytic foot processes thereby decreasing water permeability into the brain tissue.
Influence of cinaciguat on gastrointestinal motility in apo‐sGC mice
Authors: Cosyns Sarah M. R. , Huyghe Leander , Thoonen Robrecht , Stasch Johannes‐Peter , Brouckaert Peter , Lefebvre Romain A.
Published: September 2014

Background

Cinaciguat (BAY 58‐2667), an NO‐ and heme‐independent sGC activator, was shown to be more effective when the heme‐group of sGC is oxidized in vascular tissue. In apo‐sGC mice (sGCβ1His105Pheknockin) both sGC isoforms (sGCα1β1 and sGCα2β1) are heme‐deficient and can no longer be activated by NO; these mice, showing decreased gastrointestinal nitrergic relaxation and decreased gastric emptying, can be considered as a model to study the consequence of heme‐oxidation in sGC. Our aim was to compare the influence of cinaciguat, on in vitro muscle tone of gastrointestinal tissues, and on gastric emptying in WT and apo‐sGC mice.

Methods

Gastrointestinal smooth muscle strips were mounted in organ baths for isometric force recording and cGMP levels were determined by enzyme immunoassay. Protein levels of sGC subunits were assessed by immunoblotting. Gastric emptying was determined by phenol red recovery.

Key Results

Although protein levels of the sGC subunits were lower in gastrointestinal tissues of apo‐sGC mice, cinaciguat induced concentration‐dependent relaxations and increased cGMP levels in apo‐sGC fundus and colon to a similar or greater extent than in WT mice. The sGC inhibitor ODQ increased cinaciguat‐induced relaxations and cGMP levels in WT fundus and colon. In apo‐sGC antrum, pylorus and jejunum, cinaciguat was not able to induce relaxations. Cinaciguat did not improve delayed gastric emptying in apo‐sGC mice.

Conclusions & Inferences

Cinaciguat relaxes the fundus and colon efficiently when sGC is in the heme‐free condition; the non‐effect of cinaciguat in pylorus explains its inability to improve the delayed gastric emptying in apo‐sGC mice.
Reconcilable differences: a joint calibration of fine‐root turnover times with radiocarbon and minirhizotrons
Authors: Ahrens Bernhard , Hansson Karna , Solly Emily F. , Schrumpf Marion
Published: September 2014

We used bomb‐radiocarbon and raw minirhizotron lifetimes of fine roots (< 0.5 mm in diameter) in the organic layer of Norway spruce (Picea abies) forests in southern Sweden to test if different models are able to reconcile the apparently contradicting turnover time estimates from both techniques.

We present a framework based on survival functions that is able to jointly model bomb‐radiocarbon and minirhizotron data. At the same time we integrate prior knowledge about biases of both techniques – the classification of dead roots in minirhizotrons and the use of carbon reserves to grow new roots.

Two‐pool models, either in parallel or in serial setting, were able to reconcile the bomb‐radiocarbon and minirhizotron data. These models yielded a mean residence time of 3.80 ± 0.16 yr (mean ± SD). On average 60 ± 2% of fine roots turned over within 0.75 ± 0.10 yr, while the rest was turning over within 8.4 ± 0.2 yr. Bomb‐radiocarbon and minirhizotron data alone give a biased estimate of fine‐root turnover.

The two‐pool models allow a mechanistic interpretation for the coexistence of fast‐ and slow‐cycling roots – suberization and branching for the serial‐two‐pool model and branching due to ectomycorrhizal fungi–root interactions for the parallel‐two‐pool model.
Integrating ecology and physiology of root‐hemiparasitic interaction: interactive effects of abiotic resources shape the interplay between parasitism and autotrophy
Authors: Těšitel Jakub , Těšitelová Tamara , Fisher James P. , Lepš Jan , Cameron Duncan D.
Published: September 2014

Root hemiparasites are green photosynthetic plants, which parasitically acquire resources from host xylem. Mineral nutrients and water, two principal below‐ground abiotic resources, were assumed to affect the interaction between hemiparasites and their hosts. The shape of these effects and the underlying physiological mechanisms have, however, remained unclear.

We conducted a glasshouse experiment with root‐hemiparasitic Rhinanthus alectorolophus, in which we manipulated the availability of mineral nutrients and water. Biomass production and Chl fluorescence of the hemiparasites and hosts were recorded, together with proportion of host‐derived carbon in hemiparasite biomass.

The abiotic resources had profound interactive effects on the performance of both the hemiparasite and the hosts, as well as the balance of above‐ground biomass between them. These effects were mainly based on an increase of growth and photosynthetic efficiency under high nutrient concentrations, on the hemiparasite's ability to induce strong water stress on the hosts if water is limiting, and on release of the host from parasitism by simultaneous abundance of both resources.

Hemiparasitism is a highly variable interaction, in which environmental conditions affect both the parasitic and autotrophic (and thus competitive) components. A hemiparasite's own photosynthesis plays a crucial role in the assimilation of parasitized mineral resources and their transformation into growth and fitness.