bluuebunny/crossref_metadata_2025 huggingface dataset:
PFKFB3 modulates glycolytic metabolism and alleviates endoplasmic reticulum stress in human osteoarthritis cartilage
Authors: Qu Jining , Lu Daigang , Guo Hua , Miao Wusheng , Wu Ge , Zhou Meifen
Published: December 2015

Glycolytic disorder has been demonstrated to be a major cause of osteoarthritis (OA) and chondrocyte dysfunction. The present work aimed to investigate the expression and role of the glycolytic regulator 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase 3 (PFKFB3) in OA cartilage. It was found that PFKFB3 expression was down‐regulated in human OA cartilage tissues and in tumour necrosis factor (TNF)‐α‐ or interleukin (IL)‐1β‐stimulated human chondrocytes. The glycolytic metabolism appeared as glucose utilization and adenosine triphosphate (ATP) generation, and lactate production was stunted in OA cartilage. However, the impaired glycolytic process in OA cartilage was improved by PFKFB3 overexpression, which was confirmed in TNF‐α‐ or IL‐1β‐treated chondrocytes. Furthermore, the expressions of endoplasmic reticulum (ER) stress‐associated genes including PERK, ATF3, IRE1, phosphorylated eIF2α (p‐eIF2α) and MMP13 were enhanced in OA cartilage explants, while they were decreased by AdPFKFB3 transfection. PFKFB3 also modulated the expressions of PERK, ATF3, IRE1, p‐eIF2α and MMP13 in tunicamycin‐exposed chondrocytes. Additionally, PFKFB3 improved the cell viability of OA cartilage explants and chondrocytes through the PI3K/Akt/C/EBP homologous protein (CHOP) signalling pathway. The transfection of AdPFKFB3 also significantly reduced caspase 3 activation and promoted aggrecan and type II collagen expressions in OA cartilage explants and chondrocytes. In all, this study characterizes a novel role of PFKFB3 in glycolytic metabolism and ER stress of OA cartilage explants and chondrocytes. The study might provide a potential target for OA prevention or therapy.
Identification of a multi‐protein reductive dehalogenase complex in Dehalococcoides mccartyi strain CBDB1 suggests a protein‐dependent respiratory electron transport chain obviating quinone involvement
Authors: Kublik Anja , Deobald Darja , Hartwig Stefanie , Schiffmann Christian L. , Andrades Adarelys , von Bergen Martin , Sawers R. Gary , Adrian Lorenz
Published: December 2015

Dehalococcoides mccartyi strain CBDB1 is an obligate organohalide‐respiring bacterium using only hydrogen as electron donor and halogenated organics as electron acceptor. Here, we studied proteins involved in the respiratory chain under non‐denaturing conditions. Using blue native gel electrophoresis (BN‐PAGE), gel filtration and ultrafiltration an active dehalogenating protein complex with a molecular mass of 250–270 kDa was identified. The active subunit of reductive dehalogenase (RdhA) colocalised with a complex iron‐sulfur molybdoenzyme (CISM) subunit (CbdbA195) and an iron‐sulfur cluster containing subunit (CbdbA131) of the hydrogen uptake hydrogenase (Hup). No colocalisation between the catalytically active subunits of hydrogenase and reductive dehalogenase was found. By two‐dimensional BN/SDS‐PAGE the stability of the complex towards detergents was assessed, demonstrating stepwise disintegration with increasing detergent concentrations. Chemical cross‐linking confirmed the presence of a higher molecular mass reductive dehalogenase protein complex composed of RdhA, CISM I and Hup hydrogenase and proved to be a potential tool for stabilising protein–protein interactions of the dehalogenating complex prior to membrane solubilisation. Taken together, the identification of the respiratory dehalogenase protein complex and the absence of indications for quinone participation in the respiration suggest a quinone‐independent protein‐based respiratory electron transfer chain in D. mccartyi.
Dairy Foods: Current Evidence of their Effects on Bone, Cardiometabolic, Cognitive, and Digestive Health
Authors: Hess Julie M. , Jonnalagadda Satya S. , Slavin Joanne L.
Published: December 2015

Dairy foods have long been considered nutrient‐dense and health‐promoting products that offer many health benefits to their consumers. This review is an overview of the health benefits associated with them, drawing from recent research conducted on the associations of dairy food components with bone, cardiometabolic, cognitive, and digestive health in cross‐sectional and intervention studies. Each section details the associations of dairy with a certain aspect of health and focuses on the benefits milk product consumption may have on the prevention and management of chronic health conditions such as osteoporosis, the metabolic syndrome, and dementia. Dairy food components, as well as the potential biological mechanisms responsible for their effects on health, are also addressed. Although several of the biological mechanisms warrant further research, current evidence suggests that dairy consumption confers some beneficial effects to bone, cardiometabolic, cognitive, and digestive health. Due to its nutrient profile and the current evidence of its benefits, at least 1 daily serving of a dairy item is recommended by the dietary guidelines of several countries. Yet, even in the United States, many individuals do not consume the recommended 3 cups of dairy foods a day. Therefore, this review concludes with a description of the current public health impact of dairy food research as well as recommendations for the food industry to formulate dairy foods that are both palatable and health‐promoting for consumers.
Bacterial Translocation and Sample Contamination in Postmortem Microbiological Analyses
Authors: Palmiere Cristian , Egger Coraline , Prod'Hom Guy , Greub Gilbert
Published: December 2015

The diagnostic value of postmortem bacteriology has been discussed controversially for decades. In the study herein, contamination during sampling procedures and postmortem translocation were investigated to interpret postmortem microbiology results. One hundred medicolegal autopsy cases in total were included. Radiology, histology, bacteriology, and biochemistry were performed in all cases. Based on all investigation findings, 4 groups of cases were identified: death unrelated to infection, true infections, false positive (contamination during sampling procedures, postmortem translocation and mixed situations), and undetermined. The results of this study indicate that postmortem bacteriology provides useful data supporting infection‐related deaths, especially when potentially significant observations are accompanied by consistent autopsy, histology, and biochemistry. Result interpretation requires careful evaluation of number and type of isolated microorganisms.
A Novel Forensic Investigation Applied to Bone Remains Exhumed near to Quirra Interforce Firing Range
Authors: Roncati Luca , Gatti Antonietta M. , Capitani Federico , Bonacorsi Goretta , Barbolini Giuseppe , Maiorana Antonio
Published: December 2015

The need to implement novel techniques, able to support a causal link between exposure and pathology, has been emerged over the recent years. The application of scanning electron microscope coupled with probe X‐ray microanalysis (by means of an energy‐dispersive spectroscopy) has been developed by our research group for the bone remains investigation. It was aimed to testify the exposure to microsized and nanosized pollutions, due to military activities in the Quirra interforce firing range, of a Sardinian shepherd, died of acute leukemia. Metallic debris with a combustive morphology and with an oncogenic potential has been surely detected inside his bone marrow canal. This novel technique has proved to be able to bring to light a source of past exposure preserved over time within the bone marrow canal. It can be useful for postmortem analyses, delivering a new avant‐garde approach to modern forensic science.
Refreshing the Aged Latent Fingerprints with Ionizing Radiation Prior to the Cyanoacrylate Fuming Procedure: A Preliminary Study
Authors: Ristova Mimoza M. , Radiceska Pavlina , Bozinov Igorco , Barandovski Lambe
Published: December 2015

One of the crucial factors determining the cyanoacrylate deposit quality over latent fingerprints appeared to be the extent of the humidity. This work focuses on the enhancement/refreshment of age‐degraded latent fingerprints by irradiating the samples with UV, X‐ray, or thermal neutrons prior to the cyanoacrylate (CA) fuming. Age degradation of latent fingerprints deposited on glass surfaces was examined through the decrease in the number of characteristic minutiae counts over time. A term “critical day” was introduced for the time at which the average number of identifiable minutiae definitions drops to one‐half. Fingerprints older than their “critical day” were exposed to either UV, X‐ray, or thermal neutrons. Identical reference samples were kept unexposed. All samples, both reference and irradiated, were developed during a single CA fuming procedure. Comparative latent fingerprint analysis showed that exposure to ionizing radiation enhances the CA fuming, yielding a 20‐30% increase in average minutiae count.
Homemade Heavy Caliber Rifles—Two Unusual Firearms
Authors: Yalçın Sarıbey Aylin , Hannam Abigail Grace
Published: December 2015

Historically, in crimes involving heavy caliber rifles, only conventional factory‐made versions have been used. However, in recent years the number of homemade long‐barreled rifles is increasing. The characteristics of two such firearms that have been submitted to the Turkish Criminal Laboratory are discussed here. When the main parts of the guns were examined in detail, it was noted that nearly all of the parts had been made carelessly, with several structural defects visible. It was determined that the homemade heavy caliber rifles were unfit for efficient use and it was possible that they could have seriously harmed the shooter had they been fired. The development of these kinds of gun and the possibility of their use spreading throughout the country in terrorist attacks could cause a serious threat to national security.
Evaluating the Impacts of Selected Packaging Materials on the Quality Attributes of Cassava Flour (cvs. TME 419 and UMUCASS 36)
Authors: Opara Umezuruike Linus , Caleb Oluwafemi J. , Uchechukwu‐Agua Amarachi D.
Published: December 2015

The influence of packaging materials (plastic bucket, low density polyethylene [LDPE] bags and paper bags) on quality attributes of the flour of 2 cassava cultivars (TME 419 and UMUCASS 36) stored at 23 ± 2 °C and 60% relative humidity (RH) were investigated for 12 wk. Cassava flour from each package type was evaluated for proximate composition, physicochemical properties and microbial growth at 4‐wk intervals. Total color difference (∆E) of both cassava flour cultivars increased with storage duration. Flour packed in plastic bucket had the lowest change in color (3.2 ± 0.42) for cv. “TME 419ˮ and (4.1 ± 0.87) for cv. “UMUCASS 36ˮ at the end of week 12. Total carotenoid decreased across all treatment, and after the 12 wk storage, the highest total carotenoid retention (1.7 ± 0.02 and 2.0 ± 0.05 μg/mL) was observed in flour packed in plastic bucket. However, cassava flour in paper bag had the lowest microbial count of 3.4 ± 0.03 and 3.4 ± 0.08 log cfu/g for total aerobic mesophilic bacteria and fungi, respectively.
MO‐Phylogenetics: a phylogenetic inference software tool with multi‐objective evolutionary metaheuristics
Authors: Zambrano‐Vega Cristian , Nebro Antonio J. , Aldana‐Montes José F.
Published: December 2015

Phylogenetic inference is the process of searching and reconstructing the best phylogenetic tree that explains the evolution of species from a given data set. It is considered as an NP‐hard problem due to the computational complexity required to find the optimal phylogenetic trees in the space of all the possible topologies.

We have developed MO‐Phylogenetics, a software tool to infer phylogenetic trees optimizing two reconstruction criteria simultaneously, integrating a framework for multi‐objective optimization with two phylogenetic software packages.

As a result, researchers in life sciences have at their disposal a high‐performance tool including a number of multi‐objective metaheuristics that can be applied to phylogenetic inference using the maximum parsimony and maximum likelihood as objectives to be optimized at the same time.
A Large Retrospective Cohort of Patients Receiving Intravenous Olanzapine in the Emergency Department
Authors: Martel Marc L. , Klein Lauren R. , Rivard Robert L. , Cole Jon B.
Published: December 2015

Background

Olanzapine is an atypical antipsychotic with similar pharmacologic properties to droperidol. Due to the current droperidol shortage, the authors’ clinical practice has been to substitute olanzapine for droperidol in many situations. At this time, olanzapine is U.S. Food and Drug Administration approved for oral and intramuscular (IM) use only, but due to its increased utility, intravenous (IV) olanzapine was recently approved for use in the study emergency department (ED).

Objectives

The authors sought to review the use and safety of IV olanzapine in the ED patient population.

Methods

A retrospective review of consecutive patients receiving IV olanzapine between January 1, 2014, and July 1, 2014, was conducted. Data were collected via an electronic medical record review. The study was deemed exempt from informed consent by our institutional review board.

Results

A total of 713 patients received IV olanzapine during the study period. The median age was 38 years (range = 18 to 85 years), and 313 patients were male (43.9%). Primary indications for IV olanzapine administration included acute agitation (n = 245, 34.4%), abdominal pain (n = 165, 23.1%), headache (n = 121, 17.0%), nausea and vomiting (n = 107, 15.0%), pain (other; n = 60, 8.4%), and unknown (n = 15, 2.1%). IV dosing varied: 1.25 mg (n = 20, 2.8%), 2.5 mg (n = 185, 25.9%), 5 mg (n = 507, 71.1%), and 10 mg (n = 1, 0.1%). Forty‐nine patients required a second dose of olanzapine (22 IV, 26 IM, one oral). The maximum total dose of olanzapine was 20 mg. Ninety‐eight patients required a total of 146 doses of additional sedatives during their ED course. Other sedative medications included ketamine (n = 17, 2.4%), haloperidol (n = 48, 6.7%), and benzodiazepines (n = 81, 11.4%). Hypoxia was noted in 74 patients (10.4%). Major respiratory complications, including airway stimulation or repositioning maneuvers and intubation, occurred in 15 patients (2.1%). After consensus review, one intubation was classified as “likely related” to olanzapine administration, and two were classified as “possibly related” to olanzapine. Akathisia likely occurred in four patients (0.6%), and no allergic reactions were identified. Electrocardiograms (ECGs) were performed in 322 patients. A total of 251 patients had an ECG performed before olanzapine administration (median QTc = 404 ms), and 88 patients had an ECG performed after olanzapine administration (median QTc = 415 ms). Acute alcohol and drug intoxication was common, 118 (16.5%) patients were positive for ethanol, and seven of 23 drug screens were positive for sympathomimetics. Thirty‐four of 284 admissions (4.5%) were to intermediate or intensive care unit beds. No patients died while in the ED and no cases of sudden cardiac death were noted.

Conclusions

In this large retrospective review, IV olanzapine appears to be a safe in the management of a variety of ED indications. Hypoxia was common, but serious airway compromise was rare.
Using Near Infrared Spectroscopy for Tissue Oxygenation Monitoring During Procedural Sedation: The Occurrence of Peripheral Tissue Oxygenation Changes With Respiratory Depression and Supportive Airway Measures
Authors: O'Brien‐Lambert Alex , Driver Brian , Moore Johanna C. , Schick Alexandra , Miner James R.
Published: December 2015

Objectives

The objective was to assess whether respiratory depression and supportive airway measures occurring during procedural sedation are associated with changes in peripheral tissue oxygen saturation (StO2).

Methods

This was a prospective observational study of adult patients undergoing procedural sedation in the emergency department (ED). Patients undergoing sedation with propofol, 1:1 propofol and ketamine, and 4:1 propofol and ketamine were included. Clinical interventions, sedative medication doses, vital signs, end‐tidal capnography (ETCO2), pulse oximetry (SpO2), and peripheral tissue oxygen saturation (StO2) were recorded. Respiratory depression was defined as the occurrence of a recorded SpO2 < 92%, an increase in ETCO2 > 10 mm Hg from baseline, or loss of capnography waveform. Supportive airway measures documented during the procedure included bag‐valve mask ventilation, airway repositioning maneuvers, increase in supplemental oxygen, and stimulation to induce respiration. Relative changes in StO2 between baseline and nadir were compared among patients who met respiratory depression criteria or required a supportive airway measure and those who did not.

Results

Ninety‐three patients were enrolled. Thirty‐two patients (34.4%) met criteria for respiratory depression, and 31 (33.3%) required intervention in the form of a supportive airway measure. The median percent change in StO2 from procedure baseline to nadir in patients meeting criteria for respiratory depression was 13.6%, compared to 4.2% in those who did not. The change in StO2 in patients who required a supportive airway measure was 12.5% versus 5.4% in those who did not.

Conclusions

Patients with respiratory depression and the use of supportive airway measures had greater changes in StO2 during procedural sedation than in patients who did not. Peripheral tissue oxygen saturation monitoring may be a useful tool for assessing respiratory adverse events in patients undergoing procedural sedation in the ED.
Good‐quality diet in the early years may have a positive effect on academic achievement
Authors: Nyaradi Anett , Li Jianghong , Foster Jonathan K. , Hickling Siobhan , Jacques Angela , O'Sullivan Therese A. , Oddy Wendy H.
Published: December 2015

Aim

The aim of this study was to investigate the associations between early diet and academic performance during childhood.

Methods

Participants were from the Western Australian Pregnancy Cohort (Raine) Study (n = 2287). Frequency of consumption of food and beverages was collected at the one‐, two‐ and three‐year follow‐ups, using a 24‐hour food recall. Diet scores were developed from the number of eating occasions. The Western Australian Literacy and Numeracy Assessment (WALNA) data from grades five (age 10) and seven (age 12) were linked to the Raine study using The Western Australian Data Linkage System. The association between diet scores and WALNA scores was assessed using multivariate linear regression models.

Results

A higher (i.e. better quality) diet score at one year of age was associated with significantly higher scores in mathematics, reading, writing and spelling at both grades five and seven. Associations were observed between a higher diet score at two years and academic scores for mathematics, writing and spelling at grade seven. Higher dairy consumption at ages one, two and three, and higher fruit consumption at age one were associated with higher academic scores at all ages.

Conclusion

Quality of early diet may be a predictor for later academic achievement.
Impact of nitrogen inputs on multiple facets of plant biodiversity in mountain grasslands: does nutrient source matter?
Authors: Mauchamp Leslie , Mouly Arnaud , Badot Pierre‐Marie , Gillet François
Published: December 2015

Questions

What is the impact of nitrogen (N) inputs on the vegetation of mountain permanent grasslands? Beyond the effect of fertilizer quantity (total and available N supply), is there a specific effect of fertilizer quality (the various N sources) on the multiple biodiversity facets of plant communities?

Location

Jura Mountains (France).

Methods

Based on a vegetation and agronomic survey of 29 mown grasslands, we considered taxonomic, phylogenetic and multi‐trait functional diversity indices as well as community‐weighted means of seven functional traits (CWMs) including CSR strategies. Using partial redundancy analysis (pRDA) and Spearman correlations, we assessed the response of these biodiversity metrics to (1) the medium‐term total N input and the short‐term available N input of any origin, and (2) the relative contribution of industrial fertilizers, solid manure, liquid manure, livestock restitutions and atmospheric deposition to the amount of available N added to the soil during the year preceding vegetation sampling.

Results

We report significant negative rank correlations between total or available N input and two diversity metrics: species richness and functional richness. Among CWMs, high N inputs were positively correlated with specific leaf area (SLA), competitive and ruderal strategies, and negatively with seed mass and stress‐tolerant strategy. Results also revealed various trends according to the N source: when the proportion of available N from livestock restitutions was high, plant communities showed higher taxonomic and phylogenetic diversity and lower leaf dry matter content. In contrast, communities receiving mainly industrial fertilizers showed lower taxonomic and phylogenetic diversity and higher SLA. Moreover, pRDA suggested contrasting impacts of the main N source on life strategies: R strategy appeared more favoured by a high proportion of industrial fertilizers, while C strategy was enhanced by liquid or solid manure.

Conclusions

Our observations support the common finding that a high N supply impacts plant functional composition and is associated with a decrease in species richness through the loss of stress‐tolerant species. In addition, they show that biodiversity patterns mostly depend on fertilizer origin. In particular, industrial fertilizers appear to be the most detrimental sources of nutrients for both taxonomic and phylogenetic diversity in mountain grasslands.
Exploring the intracellular pharmacokinetics of the 5‐fluorouracil nucleotides during capecitabine treatment
Authors: Derissen Ellen J. B. , Jacobs Bart A. W. , Huitema Alwin D. R. , Rosing Hilde , Schellens Jan H. M. , Beijnen Jos H.
Published: December 2015

Aim

Three intracellularly formed metabolites are responsible for the antineoplastic effect of capecitabine: 5‐fluorouridine 5′‐triphosphate (FUTP), 5‐fluoro‐2′‐deoxyuridine 5′‐triphosphate (FdUTP), and 5‐fluoro‐2′‐deoxyuridine 5′‐monophosphate (FdUMP). The objective of this study was to explore the pharmacokinetics of these intracellular metabolites during capecitabine treatment.

Methods

Serial plasma and peripheral blood mononuclear cell (PBMC) samples were collected from 13 patients treated with capecitabine 1000 mg QD (group A) and eight patients receiving capecitabine 850 mg m−2 BID for fourteen days, every three weeks (group B). Samples were collected on day 1 and, for four patients of group B, also on day 14. The capecitabine and 5‐fluorouracil (5‐FU) plasma concentrations and intracellular metabolite concentrations were determined using LC–MS/MS. Pharmacokinetic parameters were estimated using non‐compartmental analysis.

Results

Only FUTP could be measured in the PBMC samples. The FdUTP and FdUMP concentrations were below the detection limits (LOD). No significant correlation was found between the plasma 5‐FU and intracellular FUTP exposure. The FUTP concentration–time profiles demonstrated considerable inter‐individual variation and accumulation of the metabolite in PBMCs. FUTP levels ranged between <LOD and 1.0 μM on day 1, and from 0.64 to 14 μM on day 14. The area under the FUTP concentration–time curve was significantly increased on day 14 of the treatment compared to day 1 (mean ± SD: 28 ± 19 μM h vs. 2.0 ± 1.9 μM h).

Conclusions

To our knowledge, this is the first time that intracellular FUTP concentrations were measured in patients treated with capecitabine. During 14 days of treatment with capecitabine twice daily, intracellular accumulation of FUTP occurs.
The circle of life: A cross‐cultural comparison of children's attribution of life‐cycle traits
Authors: Burdett Emily R. R. , Barrett Justin L.
Published: December 2015

Do children attribute mortality and other life‐cycle traits to all minded beings? The present study examined whether culture influences young children's ability to conceptualize and differentiate human beings from supernatural beings (such as God) in terms of life‐cycle traits. Three‐to‐5‐year‐old Israeli and British children were questioned whether their mother, a friend, and God would be subject to various life‐cycle processes: Birth, death, ageing, existence/longevity, and parentage. Children did not anthropomorphize but differentiated among human and supernatural beings, attributing life‐cycle traits to humans, but not to God. Although 3‐year‐olds differentiated significantly among agents, 5‐year‐olds attributed correct life‐cycle traits more consistently than younger children. The results also indicated some cross‐cultural variation in these attributions. Implications for biological conceptual development are discussed.
Disrupted attentional learning in high schizotypy: Evidence of aberrant salience
Authors: Haselgrove Mark , Le Pelley Mike E. , Singh Navreen K. , Teow Hui Qi , Morris Richard W. , Green Melissa J. , Griffiths Oren , Killcross Simon
Published: December 2015

The relationship between learned variations in attention and schizotypy was examined in two experiments. In Experiment 1, participants low on a negative subscale of schizotypy exhibited an explicit bias in overt attention towards stimuli that were established as predictive of a trial outcome, relative to stimuli that were irrelevant. The same participants also showed a bias in learning about these stimuli when they presented in a novel context. Neither of these effects was observed in participants high in schizotypy. In Experiment 2, participants low on the negative subscale of schizotypy exhibited faster reaction times towards a target that was cued by a stimulus that had a history of predictive validity relative to a stimulus that had a history of irrelevance. Again, this effect was not present in participants high in schizotypy. These results imply a disruption in the normal allocation of attention to cues that have predictive significance in schizotypy.
Spatial Language and the Embedded Listener Model in Parents’ Input to Children
Authors: Ferrara Katrina , Silva Malena , Wilson Colin , Landau Barbara
Published: December 2015

Language is a collaborative act: To communicate successfully, speakers must generate utterances that are not only semantically valid but also sensitive to the knowledge state of the listener. Such sensitivity could reflect the use of an “embedded listener model,” where speakers choose utterances on the basis of an internal model of the listener's conceptual and linguistic knowledge. In this study, we ask whether parents’ spatial descriptions incorporate an embedded listener model that reflects their children's understanding of spatial relations and spatial terms. Adults described the positions of targets in spatial arrays to their children or to the adult experimenter. Arrays were designed so that targets could not be identified unless spatial relationships within the array were encoded and described. Parents of 3–4‐year‐old children encoded relationships in ways that were well‐matched to their children's level of spatial language. These encodings differed from those of the same relationships in speech to the adult experimenter (Experiment 1). In contrast, parents of individuals with severe spatial impairments (Williams syndrome) did not show clear evidence of sensitivity to their children's level of spatial language (Experiment 2). The results provide evidence for an embedded listener model in the domain of spatial language and indicate conditions under which the ability to model listener knowledge may be more challenging.
A comparison of propofol–midazolam and midazolam alone for sedation in endobronchial ultrasound‐guided transbronchial needle aspiration: a retrospective cohort study
Authors: Öztaş Selahattin , Aka Aktürk Ülkü , Alpay Levent A. , Meydan Burhan , Ogün Hamza , Taylan Mahşuk , Yalçınsoy Murat , Çalışır Haluk C. , Görgüner Ali Metin , Ernam Dilek
Published: December 2015

Objectives

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is a new, minimally invasive, bronchoscopic technique used in the evaluation of inthrathoracic lymph nodes.Use of sedation drugs before the procedure differs among centres. There is no standardization about sedation before EBUS‐TBNA.We used a policy decision to shift from use of propofol with midazolam vs midazolam alone in a large tertiary hospital to evaluate the diagnostic yield and safety of EBUS‐TBNA procedure.

Methods

Files of all the patients who were performed EBUS‐TBNA between the dates of September 2010 and May 2014 were surveyed. All the EBUS‐TBNA cases were performed under sedation of propofol and midazolam with an accompanying anesthesiologist in the beginning, however, sedation is applied with midazolam without an accompanying anesthesiologist after April 2013 due to changes in sedation policy. The diagnostic yield and complication rates were compared by chi‐squared analysis between two groups.

Results

The files of 340 EBUS‐TBNA performed patients were evaluated. Of the patients 274 eligible patients were analysed. 152 patients who fulfilled the inclusion criteria were analysed in propofol‐midazolam (P) sedated group and 122 patients were analysed in midazolam (M) group. There is no statistically significant difference between two different sedated groups in terms of age and gender. Diagnostic value was detected as 77.6% in P group and 85.7% in M group and the difference was not statistically significant. No difference between complication rates of both groups was observed.

Conclusion

Both sedation‐types for performing EBUS‐TBNA showed similar diagnostic value and complication rates in our study. Propofol with midazolam application requires with an accompanying anaesthesiologist, therefore, it increases cost. EBUS‐TBNA procedures had been performed in safe with no decrease in diagnostic yield under moderate sedation.
Pedunculated Pulmonary Artery Sarcoma Suggested by Transthoracic Echocardiography
Authors: Wang Xiaobing , Ren Weidong , Yang Jun
Published: December 2015

Pulmonary artery sarcoma (PAS) is an extremely rare malignancy. It is usually found after it grows large enough to occupy almost the entire lumen of the pulmonary artery and causes serious clinical symptoms. Thus, it is usually difficult to distinguish PAS from pulmonary thromboembolism based on imaging examinations. Few case reports had shown the attachment of PAS to pulmonary artery, a key characteristic for diagnosis, and differential diagnosis of PAS. In this case, we found a PAS, which did not cause local obstruction and some tumor emboli, which obstructed the branches of the pulmonary arteries and caused pulmonary hypertension and clinical symptoms. Transthoracic echocardiography (TTE) revealed a part of the tumor attached to the intima of the main pulmonary artery with a peduncle and had obvious mobility, which was suggestive of PAS and differentiated it from the pulmonary thromboembolism. To our knowledge, this is the first case report of a pedunculated PAS suggested by TTE. Combined with pulmonary artery computed tomography angiography, the diagnosis of PAS is strongly suggested before the operation. This case indicates that TTE could reveal the attachment and mobility of PAS in the main pulmonary and may provide useful information for the diagnosis and differential diagnosis of PAS, especially a pedunculated PAS.
Response loss and development of neutralizing antibodies during long‐term treatment with romiplostim in patients with immune thrombocytopenia: a case series
Authors: Carpenedo Monica , Cantoni Silvia , Coccini Veronica , Pogliani Enrico Maria , Cairoli Roberto
Published: December 2015

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts resulting from both immune‐mediated platelet destruction and inappropriate bone marrow platelet production. Therefore, in patients with ITP failing immunosuppressants/splenectomy, an alternative approach is to enhance platelet production stimulating thrombopoiesis. Studies on the development of recombinant thrombopoietins (rhTPO) were halted as a minority of patients developed an autoantibody that neutralized pegylated rhTPO and also cross‐reacted with and neutralized endogenous TPO resulting in thrombocytopenia. Clinical use of romiplostim, a second‐generation TPO‐RAs, has shown that during long‐term treatment, it may elicit the development of neutralizing antibodies to this agent resulting in acute thrombocytopenia. In our case series of 47 primary adult patients with ITP treated with romiplostim, 28 of 47 are evaluable for response loss. Among these, we observed eight patients who either progressively (3 of 8) or abruptly (5 of 8) lost response which accounts for a prevalence of 28.5%. Neutralizing antibody testing could be performed in 4 of 8 patients and 3 of 4 tested positive. These antibodies did not cross‐react with endogenous TPO and retesting of 2 patients at 9 and 7 months yielded a negative result. At follow‐up, 5 of 8 patients – including the 3 patients with neutralizing antibodies – went into long‐term complete response when switched to a different therapy while 3 of 8 patients never regained a response on subsequent lines of therapy. Response loss does not seem to be so rare an event during romiplostim administration (28.5% in our series) and in a minority of patients, it can be associated with development of drug neutralizing antibodies. Although recognized by the manufacturer as a possible adverse event ensuing during romiplostim administration, development of neutralizing antibody in everyday clinical practice has so far not been specifically addressed in reports on romiplostim use outside controlled studies. Unfortunately, testing for these antibodies requires adhesion to strict procedures which is not easily accomplished in everyday clinical practice. This complexity represents a significant drawback in extending antibody testing to all patients who lose response to romiplostim.
Human focal seizures are characterized by populations of fixed duration and interval
Authors: Cook Mark J. , Karoly Philippa J. , Freestone Dean R. , Himes David , Leyde Kent , Berkovic Samuel , O'Brien Terence , Grayden David B. , Boston Ray
Published: December 2015

Objective

We report on a quantitative analysis of data from a study that acquired continuous long‐term ambulatory human electroencephalography (EEG) data over extended periods. The objectives were to examine the seizure duration and interseizure interval (ISI), their relationship to each other, and the effect of these features on the clinical manifestation of events.

Methods

Chronic ambulatory intracranial EEG data acquired for the purpose of seizure prediction were analyzed and annotated. A detection algorithm identified potential seizure activity, which was manually confirmed. Events were classified as clinically corroborated, electroencephalographically identical but not clinically corroborated, or subclinical. K‐means cluster analysis supplemented by finite mixture modeling was used to locate groupings of seizure duration and ISI.

Results

Quantitative analyses confirmed well‐resolved groups of seizure duration and ISIs, which were either mono‐modal or multimodal, and highly subject specific. Subjects with a single population of seizures were linked to improved seizure prediction outcomes. There was a complex relationship between clinically manifest seizures, seizure duration, and interval.

Significance

These data represent the first opportunity to reliably investigate the statistics of seizure occurrence in a realistic, long‐term setting. The presence of distinct duration groups implies that the evolution of seizures follows a predetermined course. Patterns of seizure activity showed considerable variation between individuals, but were highly predictable within individuals. This finding indicates seizure dynamics are characterized by subject‐specific time scales; therefore, temporal distributions of seizures should also be interpreted on an individual level. Identification of duration and interval subgroups may provide a new avenue for improving seizure prediction.
Environmental influences on mosquito foraging and integrated vector management can delay the evolution of behavioral resistance
Authors: Stone Chris , Chitnis Nakul , Gross Kevin
Published: December 2015

Along with the scaled‐up distribution of long‐lasting insecticidal nets for malaria control has become concern about insecticide resistance. A related concern regards the evolution of host‐seeking periodicity from the nocturnal to the crepuscular periods of the day. Why we observe such shifts in some areas but not others and which methods could prove useful in managing such behavioral resistance remain open questions. We developed a foraging model to explore whether environmental conditions affect the evolution of behavioral resistance. We looked at the role of the abundance of blood hosts and nectar sources and investigated the potential of attractive toxic sugar baits for integrated control. Higher encounter rates with hosts and nectar sources allowed behaviorally resistant populations to persist at higher levels of bed net coverage. Whereas higher encounter rates with nectar increased the threshold where resistance emerged, higher encounter rates of hosts lowered this threshold. Adding sugar baits lowered the coverage level of bed nets required to eliminate the vector population. In certain environments, using lower bed net coverage levels together with toxic sugar baits may delay or prevent the evolution of behavioral resistance. Designing sustainable control strategies will depend on an understanding of vector behavior expressed in local environmental conditions.
Shrubline but not treeline advance matches climate velocity in montane ecosystems of south‐central Alaska
Authors: Dial Roman J. , Scott Smeltz T. , Sullivan Patrick F. , Rinas Christina L. , Timm Katriina , Geck Jason E. , Carl Tobin S. , Golden Trevor S. , Berg Edward C.
Published: December 2015

Tall shrubs and trees are advancing into many tundra and wetland ecosystems but at a rate that often falls short of that predicted due to climate change. For forest, tall shrub, and tundra ecosystems in two pristine mountain ranges of Alaska, we apply a Bayesian, error‐propagated calculation of expected elevational rise (climate velocity), observed rise (biotic velocity), and their difference (biotic inertia). We show a sensitive dependence of climate velocity on lapse rate and derive biotic velocity as a rigid elevational shift. Ecosystem presence identified from recent and historic orthophotos ~50 years apart was regressed on elevation. Biotic velocity was estimated as the difference between critical point elevations of recent and historic logistic fits divided by time between imagery. For both mountain ranges, the 95% highest posterior density of climate velocity enclosed the posterior distributions of all biotic velocities. In the Kenai Mountains, mean tall shrub and climate velocities were both 2.8 m y−1. In the better sampled Chugach Mountains, mean tundra retreat was 1.2 m y−1and climate velocity 1.3 m y−1. In each mountain range, the posterior mode of tall woody vegetation velocity (the complement of tundra) matched climate velocity better than either forest or tall shrub alone, suggesting competitive compensation can be important. Forest velocity was consistently low at 0.1–1.1 m y−1, indicating treeline is advancing slowly. We hypothesize that the high biotic inertia of forest ecosystems in south‐central Alaska may be due to competition with tall shrubs and/or more complex climate controls on the elevational limits of trees than tall shrubs. Among tall shrubs, those that disperse farthest had lowest inertia. Finally, the rapid upward advance of woody vegetation may be contributing to regional declines in Dall's sheep (Ovis dalli), a poorly dispersing alpine specialist herbivore with substantial biotic inertia due to dispersal reluctance.
Miscanthus as biogas substrate – cutting tolerance and potential for anaerobic digestion
Authors: Kiesel Andreas , Lewandowski Iris
Published: December 2015

In the anaerobic digestion and biogas industry in Germany, the step of energy crop production accounts for a high proportion of the greenhouse gas emissions and environmental impacts. Replacing annual energy crops, for example maize, by perennial biomass crops such as miscanthus offers the potential to increase the sustainability of biogas crop production. However, the cutting tolerance of miscanthus and the mechanisms influencing it need to be investigated to assess its potential as a biogas crop. For this purpose, a field trial with different harvest regimes was conducted to identify the potential methane yield and cutting tolerance of Miscanthus x giganteus. Several fertilization regimes were tested under nitrogen‐limited conditions in a pot trial to investigate the mechanisms behind the cutting tolerance. The refilling of carbohydrate (starch) stores in the rhizome was identified as a very important factor influencing the cutting tolerance of miscanthus, whereas the nutrient relocation appeared to be of less importance. The field trial revealed that Miscanthus x giganteus offers a very high methane yield potential of approx. 6000 m3 ha−1 when harvested in October, which is within the range of the methane hectare yield of energy maize. The substrate‐specific methane yield of Miscanthus x giganteus biomass decreased with later harvest dates and reached 247 ml (g oDM)−1 in October. This harvest date delivered very high, stable yields of on average 26 t DM ha−1 over two years and enabled a good cutting tolerance. Green harvest in October was identified to be suitable for Miscanthus x giganteus and is recommended for biogas utilization. In conclusion, the perennial biomass crop Miscanthus x giganteus is a very promising biogas crop and offers the potential to increase the sustainability of the anaerobic digestion sector in Germany by replacing a substantial area of biogas maize cultivation.
Radiation capture and conversion efficiencies of Miscanthus sacchariflorus, M. sinensis and their naturally occurring hybrid M. × giganteus
Authors: Davey Christopher Lyndon , Jones Laurence Edmund , Squance Michael , Purdy Sarah Jane , Maddison Anne Louise , Cunniff Jennifer , Donnison Iain , Clifton‐Brown John
Published: December 2015

Miscanthus is a rhizomatous C4 grass of great interest as a biofuel crop because it has the potential to produce high yields over a wide geographical area with low agricultural inputs on marginal land less suitable for food production. At the moment, a clonal interspecific hybrid Miscanthus × giganteus is the most widely cultivated and studied in Europe and the United States, but breeding programmes are developing newer more productive varieties. Here, we quantified the physiological processes relating to whole season yield in a replicated plot trial in Wales, UK. Light capture and conversion efficiency were parameterized for four carefully selected genotypes (M. sinensis, M. sacchariflorus and Miscanthus × giganteus). Differences in the canopy architecture in mature stands as measured by the extinction coefficient (k) were small (0.55–0.65). Sensitivity analysis on a mathematical model of Miscanthus was performed to quantify the accumulative intercepted photosynthetically active radiation (iPAR) in the growing season using (i) k, (ii) variation in the thermal responses of leaf expansion rate, (iii) base temperature for degree days and (iv) date start of canopy expansion. A 10% increase in k or leaf area per degree day both had a minimal effect on iPAR (3%). Decreasing base temperature from 10 to 9 °C gave an 8% increase in iPAR. If the starting date for canopy expansion was the same as shoot emergence date, then the iPAR increases by 12.5%. In M. × giganteus, the whole season above ground and total (including below ground) radiation‐use efficiency (RUE) ranged from 45% to 37% higher than the noninterspecific hybrid genotypes. The greater yields in the interspecific hybrid M. × giganteus are explained by the higher RUE and not by differences in iPAR or partitioning effects. Studying the mechanisms underlying this complex trait could have wide benefits for both fuel and food production.
Rescuing failed oral implants via Wnt activation
Authors: Yin Xing , Li Jingtao , Chen Tao , Mouraret Sylvain , Dhamdhere Girija , Brunski John B. , Zou Shujuan , Helms Jill A.
Published: December 2015

Aim

Implant osseointegration is not always guaranteed and once fibrous encapsulation occurs clinicians have few options other than implant removal. Our goal was to test whether a WNT protein therapeutic could rescue such failed implants.

Material and Methods

Titanium implants were placed in over‐sized murine oral osteotomies. A lack of primary stability was verified by mechanical testing. Interfacial strains were estimated by finite element modelling and histology coupled with histomorphometry confirmed the lack of peri‐implant bone. After fibrous encapsulation was established peri‐implant injections of a liposomal formulation of WNT3A protein (L‐WNT3A) or liposomal PBS (L‐PBS) were then initiated. Quantitative assays were employed to analyse the effects of L‐WNT3A treatment.

Results

Implants in gap‐type interfaces exhibited high interfacial strains and no primary stability. After verification of implant failure, L‐WNT3A or L‐PBS injections were initiated. L‐WNT3A induced a rapid, significant increase in Wnt responsiveness in the peri‐implant environment, cell proliferation and osteogenic protein expression. The amount of peri‐implant bone and bone in contact with the implant were significantly higher in L‐WNT3A cases.

Conclusions

These data demonstrate L‐WNT3A can induce peri‐implant bone formation even in cases where fibrous encapsulation predominates.
The association between shallow vestibular depth and peri‐implant parameters: a retrospective 6 years longitudinal study
Authors: Halperin‐Sternfeld Michal , Zigdon‐Giladi Hadar , Machtei Eli E.
Published: December 2015

Aim

The aim of this study was to retrospectively evaluate the association between shallow vestibular depth (VD) and peri‐implant parameters.

Material and Methods

Peri‐implant parameters were evaluated in 61 periodontal patients under regular supportive periodontal therapy. Clinical parameters included gingival index (GI), plaque index (PI), bleeding on probing (BOP), peri‐implant pocket depths (PPD), mucosal recession (MR), relative attachment level (RAL), width and thickness of keratinized mucosa (KMW, KMT) and VD. Radiographic bone level (RBL) was measured on peri‐apical radiographs.

Results

Sites with shallow VD (≤4 mm) were associated with higher MR (0.91 mm versus 0.47 mm, p ≤ 0.009), higher RAL (4.23 mm versus 3.59 mm, p ≤ 0.0001) and higher RBL (2.18 mm versus 1.7 mm, p = 0.05) when compared with adequate vestibular depth sites (VD >4 mm). Moreover, sites with shallow VD presented lower KMW compared with sites with adequate VD (1.24 mm versus 2.38 mm, respectively, p ≤ 0.0001). Slightly greater BOP, and GI were recorded for the shallow VD compared with adequate sites. According to multivariate analysis, factors that could predict RAL included: VD, GI, age, supporting periodontal therapy, implant type and design.

Conclusions

Based on this study, inadequate vestibular depth around dental implants may be associated with increased peri‐implant bone loss and mucosal recession. Further prospective and intervention studies will be required to fully understand this phenomenon.