bluuebunny/crossref_metadata_2025 huggingface dataset:
A consensus to determine the ideal critical care transfer bag
Authors: Van Zwanenberg Gezz , Dransfield Melissa , Juneja Rohit ,   On behalf of and for North West London Critical Care Network
Published: July 2016

Background

Familiarity with environment, processes and equipment reduces the risk inherently associated with critical care transfers. Therefore, the North West London Critical Care Network decided to create a standardised ideal transfer bag and contents to improve patient safety.

Methods

A four-round modified Delphi survey developed a condensed and clinically tested content list. An expert panel then designed an ideal transfer bag based on agreed important principles.

Results

Participants completed two rounds of an electronic survey. Round 3 comprised an expert clinical panel review, while round 4 tested the contents over 50 clinical transfers. The prototype bag’s design was adjusted after clinical use and feedback.

Discussion

This project has introduced a standardised critical care transfer bag across our network. A similar technique could be used for other healthcare regions. Alternatively, the above critical care transfer bag could be adopted or adapted for regional use by clinicians.
Co-trimoxazole-induced hypoglycaemia in an immunosuppressed intensive care patient
Authors: Richards Katherine A , Raby Simon
Published: July 2016

An 18-year-old female inpatient on a neurosciences intensive care unitwith new onset super-refractory epilepsy became hypoglycaemic 48 h after commencing co-trimoxazole. She had been placed on this for prophylaxis against Pneumocystis jiroveci infection in the context of significant immunosuppression with high-dose corticosteroid therapy. In order to maintain glucose control, she required a continuous infusion of 10% dextrose at rates of 15–25 ml/h. Recurrent attempts to wean this were limited by further hypoglycaemia, until she spontaneously regained normoglycaemia after 73 days. This case report will discuss this unusual case of refractory hypoglycaemia, and the proposed pathophysiology of hypoglycaemia related to co-trimoxazole therapy.
Prediagnosis aspirin use and outcomes in a prospective cohort of esophageal cancer patients
Authors: Araujo James L. , Altorki Nasser K. , Sonett Joshua R. , Rodriguez Adriana , Sungur-Stasik Kivilcim , Spinelli Cathy F. , Neugut Alfred I. , Abrams Julian A.
Published: July 2016

Background:

Esophageal cancer remains associated with poor outcomes, yet little is known regarding factors that influence survival. Aspirin use prior to cancer diagnosis may influence outcomes. We aimed to assess the effects of prediagnosis aspirin use in patients with esophageal cancer.

Methods:

We conducted a prospective cohort study of newly-diagnosed esophageal cancer patients at two tertiary care centers. We assessed history of prediagnosis aspirin use, and prospectively followed patients and assessed mortality, cause of death, and development of metastases.

Results:

We enrolled 130 patients, the majority of whom were male (81.5%) and had adenocarcinoma (80.8%). Overall, 57 patients (43.9%) were regular aspirin users. In unadjusted analyses, we found no difference in all-cause mortality between aspirin users and nonusers. In multivariate analyses, prediagnosis aspirin use was not associated with all-cause mortality [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.48–1.57] or esophageal cancer-specific mortality (HR 1.07, 95% CI 0.52–2.21). Prediagnosis aspirin use was associated with a significantly increased risk of interval metastasis (HR 3.59, 95% CI 1.08–11.96).

Conclusions:

In our cohort of esophageal cancer patients, prediagnosis aspirin use was not associated with all-cause or cancer-specific mortality. However, risk of interval metastatic disease was increased among those who took aspirin regularly prediagnosis. Future studies are warranted to assess whether aspirin influences the molecular characteristics of esophageal tumors, with potential prognostic and therapeutic implications.
Level of patient–physician agreement in assessment of change following conservative rehabilitation for shoulder pain
Authors: Moore-Reed Stephanie D. , Kibler W. Ben , Bush Heather , Uhl Tim L.
Published: July 2016

Background

Assessment of health-related status has been shown to vary between patients and physicians, although the degree of patient–physician discordance in the assessment of the change in status is unknown.

Methods

Ninety-nine patients with shoulder dysfunction underwent a standardized physician examination and completed several self-reported questionnaires. All patients were prescribed the same physical therapy intervention. Six weeks later, the patients returned to the physician, when self-report questionnaires were re-assessed and the Global Rating of Change (GROC) was completed by the patient. The physician completed the GROC retrospectively. To determine agreement between patient and physician, intra-class correlation (ICC) coefficient and Pearson’s r using the 15-point GROC and weighted kappa using a consolidated three-point GROC were calculated.

Results

Utilizing the 15-point GROC, complete agreement was observed in 37 of 99 patients (37%). ICC and Pearson’s r between patient and physician were 0.62 and 0.63, respectively. Utilizing a consolidated three-point GROC, complete agreement was observed in 76 of 99 patients (77%). Weighted kappa was 0.62.

Conclusions

Assessment of change reported by the patient demonstrates moderate to good agreement with physician assessment. These findings indicate that the GROC does reflect and represent similar assessment of change in health status by patients and physicians. This can aid discussion of both past treatment results and future treatment plans.
Glycated Hemoglobin, Plasma Glucose, and Erythrocyte Aging
Authors: Beltran del Rio Manuel , Tiwari Mukesh , Amodu Leo I , Cagliani Joaquin , Rodriguez Rilo Horacio Luis
Published: July 2016

Background:

The relationship between HbA1c and blood glucose averages has been characterized many times, yet, a unifying, mechanistic description is still lacking.

Methods:

We calculated the level of HbA1c from plasma glucose averages based solely on the in vivo rate of hemoglobin glycation, and the different turnover rates for erythrocytes of different ages. These calculations were then compared to the measured change of HbA1c due to changes in mean blood glucose (MBG), to complex models in the literature, and our own experiments.

Results:

Analysis of data on erythrocyte ageing patterns revealed that 2 separate RBC turnover mechanisms seem to be present. We calculated the mean red blood cell (RBC) life span within individuals to lie between 60 and 95 days. Comparison of expected HbA1c levels to data taken from continuous glucose monitors and finger-stick MBG yielded good agreement ( r = .87, P < .0001). Experiments on the change with time of HbA1c induced by a change of MBG were in excellent agreement with our calculations ( r = .98, P < .0001).

Conclusions:

RBC turnover seems to be dominated by a constant rate of cell loss, and a mechanism that targets cells of a specific age. Average RBC life span is 80 ± 10.9 days. Of HbA1c change toward treatment goal value, 50% is reached in about 30 days. Many factors contribute to the ratio of glycated hemoglobin, yet we can make accurate estimations considering only the in vivo glycation constant, MBG, and the age distribution of erythrocytes.
Jam Injuries of the Finger
Authors: Carruthers Katherine H. , Skie Martin , Jain Margaret
Published: July 2016

Context:

Jam injuries of the finger are frequently encountered in general orthopaedic and sports medicine practice. The finger joints in particular are very susceptible to traumatic injury, but in the absence of severe deformity, digital trauma is often downplayed in the hopes of a more rapid return to game play.

Evidence Acquisition:

Articles published from 1966 to 2015 were reviewed to capture historical and current views on the presentation, diagnosis, and treatment of jam injuries in athletes.

Study Design:

Clinical review.

Level of Evidence:

Level 5.

Results:

Although jam injuries are frequently grouped together, they represent a host of injuries that can be challenging to differentiate. A thorough knowledge of finger joint anatomy and injury mechanism is critical to perform an appropriate examination, establish an accurate diagnosis, and identify a treatment plan for each patient.

Conclusion:

Every member of the athletic care team must be aware of the spectrum of digital injuries, including the basic signs present on examination, which may indicate the need for more formal workup. Additionally, preventing injury through athlete education is paramount to athletic care.
Treatment of multiple myeloma with the immunostimulatory SLAMF7 antibody elotuzumab
Authors: Einsele Hermann , Schreder Martin
Published: July 2016

Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells. In combination with lenalidomide and low-dose dexamethasone, elotuzumab has shown remarkable effects in patients with relapsed or refractory multiple myeloma. In these patients, the risk of disease progression or death was significantly reduced by 30% on elotuzumab. Currently, elotuzumab is being evaluated in various myeloma patient populations and combination regimens. This review discusses the use of elotuzumab as an antimultiple myeloma agent and provides an update on the results of recent clinical trials evaluating the safety and efficacy of elotuzumab for the treatment of multiple myeloma.
Antipsychotic use in dementia: a systematic review of benefits and risks from meta-analyses
Authors: Tampi Rajesh R. , Tampi Deena J. , Balachandran Silpa , Srinivasan Shilpa
Published: July 2016

Background:

The purpose of this review is to evaluate the data on the use of antipsychotics in individuals with dementia from meta-analyses.

Methods:

We performed a literature search of PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases through 30 November, 2015 using the following keywords: ‘antipsychotics’, ‘dementia’ and ‘meta-analysis’. The search was not restricted by the age of the patients or the language of the study. However, in the final analysis we only included studies involving patients that were published in English language journals or had official English translations. In addition, we reviewed the bibliographic databases of published articles for additional studies.

Results:

This systematic review of the literature identified a total of 16 meta-analyses that evaluated the use of antipsychotics in individuals with dementia. Overall, 12 meta-analyses evaluated the efficacy of antipsychotics among individuals with dementia. Of these, eight also assessed adverse effects. A further two studies evaluated the adverse effects of antipsychotics (i.e. death). A total of two meta-analyses evaluated the discontinuation of antipsychotics in individuals with dementia. Overall, three meta-analyses were conducted in individuals with Alzheimer’s disease (AD) whereas one focused on individuals with Lewy Body Dementia (LBD). The rest of the 12 meta-analyses included individuals with dementia.

Conclusions:

Antipsychotics have demonstrated modest efficacy in treating psychosis, aggression and agitation in individuals with dementia. Their use in individuals with dementia is often limited by their adverse effect profile. The use of antipsychotics should be reserved for severe symptoms that have failed to respond adequately to nonpharmacological management strategies.
Faculty Perceived Barriers and Attitudes Toward Peer Review of Classroom Teaching in Higher Education Settings
Authors: Teoh Siew Li , Ming Long Chiau , Khan Tahir Mehmood
Published: July 2016

Peer review of teaching (PRT) is one of the various assessment methods employed to assess teaching effectiveness. The current meta-synthesis aims to summarize the faculty perceived barriers and attitudes toward PRT process. A systematic search was done across a range of databases, with 26 studies being found acceptable for data extraction. Because all the data were presented in narrative form only, no statistical test was applied to assess the significance, difference, or association between the variables. A thematic analysis was performed, which identified the following significant issues: the importance of the involvement of teaching experts in the PRT process, the content of PRT and quality of feedback, objectives associated with PRT, and faculty perceived barriers to PRT. Overall, it is shown that academic culture, time-related issues, and the need for restructured PRT guidelines are common barriers to a willingness to participate in PRT.
“Mindless Medicals”
Authors: Michell Karen Elizabeth , Rispel Laetitia C.
Published: July 2016

This article explores stakeholders’ perceptions of the quality of occupational health service (OHS) delivery in South Africa. Using a purposive sampling technique, 11 focus group discussions (FGDs) were conducted in three provinces. Focus group participants ( n = 69) were recruited through professional organizations of occupational physicians and occupational health nurses as well as employer representatives of major industries in South Africa. Transcriptions of FGDs were analyzed using thematic content analysis. South Africa has diverse models of OHS delivery with varying quality. Focus group participants criticized the outsourced model of service delivery and the excessive focus on physical examinations to achieve legal compliance. These problems are exacerbated by a perceived lack of employer emphasis on occupational health, insufficient human and financial resources, and lack of specific quality of care standards for occupational health. Improvement in the quality of OHS delivery is essential to realize South Africa’s quest for universal health coverage.
Workplace Bullying Among the Nursing Staff of Greek Public Hospitals
Authors: Karatza Christine , Zyga Sofia , Tziaferi Styliani , Prezerakos Panagiotis
Published: July 2016

In this quantitative, cross-sectional study, the authors identified the impact of workplace bullying on nursing staff employed at select Greek public hospitals. They conducted the study using the Negative Acts Questionnaire with a convenience sample of 841 participants employed by five Greek hospitals in the 1st Regional Health Authority of Attica. One third of the respondents reported having been psychologically harassed at work in the past 6 months. According to the results, the impact workplace bullying has on nursing staff varies depending on the existence of a supportive familial or friend environment and if nurses parent children. These findings demonstrate the value of family and friend support when coping with workplace bullying.
An Uncommon Association of Familial Partial Lipodystrophy, Dilated Cardiomyopathy, and Conduction System Disease
Authors: Panikkath Ragesh , Panikkath Deepa , Sanchez-Iglesias S. , Araujo-Vilar D , Lado-Abeal Joaquin
Published: July 2016

A 46-year-old African American woman presented with severe respiratory distress requiring intubation and was diagnosed with nonischemic cardiomyopathy. She had the typical phenotype of familial partial lipodystrophy 2 (FPLD2). Sequence analysis of LMNA gene showed a heterozygous missense mutation at exon 8 (c.1444C>T) causing amino acid change, p.R482W. She later developed severe coronary artery disease requiring multiple percutaneous coronary interventions and coronary artery bypass surgery. She was later diagnosed with diabetes, primary hyperparathyroidism, and euthyroid multinodular goiter. She had sinus nodal and atrioventricular nodal disease and had an implantable cardioverter defibrillator implantation due to persistent left ventricular dysfunction. The device eroded through the skin few months after implantation and needed a re-implant on the contralateral side. She had atrial flutter requiring ablation. This patient with FPLD2 had most of the reported cardiac complications of FPLD2. This case is presented to improve the awareness of the presentation of this disease among cardiologists and internists.
The Effects of Grids on Web Surveys Completed with Mobile Devices
Authors: Stern Michael , Sterrett David , Bilgen Ipek
Published: July 2016

Question grids are common on Web surveys, and studies show that grids can affect how respondents complete surveys. However, there is little research that investigates the effects of grids on Web surveys completed on mobile devices. In this article, we evaluate the effects of question grids on response quality and measurement error for surveys taken on phones or tablets. Our study draws on a probabilistic Web survey. The survey included an experiment in which respondents were assigned to one of three question format conditions: one large grid, two small grids, or single item per page. We analyze how question grids affect response times and nondifferentiation as well as explore the interaction effects between grids and devices. Reductions in time associated with question grids were greater for surveys completed on mobile devices as opposed to those completed on computers. Likewise, the increases in nondifferentiation associated with question grids were greater for surveys completed on mobile devices. We find that effects of question grids on responses in Web surveys can differ across devices, and so researchers should be cautious of using grids on Web surveys as more people opt to do surveys on phones or tablets.
Comparative Analysis of the Genocidal Process: Holocaust and the Genocide against the Tutsi
Authors: Nikuze Donatien
Published: July 2016

The Holocaust and genocide against the Tutsi occurred in the twentieth century. To document and promote greater understanding of genocide, it is essential to compare events of the Holocaust with the genocide against the Tutsi. The main purpose is not to compare pain, but rather to understand the complex social phenomenon through a detailed evaluation of existing official and unofficial accounts of historical events as documented by public records, private diaries, books, newspapers, journals, and other periodicals. By outlining the key moments that led to both genocides, it is possible to shed light on the nature of the genocide itself and although different, the Holocaust and the genocide against the Tutsi share certain common elements.
Developing HSCs become Notch independent by the end of maturation in the AGM region
Authors: Souilhol Céline , Lendinez Javier G. , Rybtsov Stanislav , Murphy Fiona , Wilson Heather , Hills David , Batsivari Antoniana , Binagui-Casas Anahí , McGarvey Alison C. , MacDonald H. Robson , Kageyama Ryoichiro , Siebel Christian , Zhao Suling , Medvinsky Alexander
Published: July 2016

Key Points

Both Notch1 and Notch2 receptors are involved in pre-HSC maturation. Developing HSCs become Notch independent by the end of their maturation in the AGM region.
Game theory models for communication between agents: a review
Authors: Farooqui Aisha D. , Niazi Muaz A.
Published: July 2016

In the real world, agents or entities are in a continuous state of interactions. These interactions lead to various types of complexity dynamics. One key difficulty in the study of complex agent interactions is the difficulty of modeling agent  communication on the basis of rewards. Game theory offers a perspective of analysis and modeling these interactions. Previously, while a large amount of literature is available on game theory, most of it is from specific domains and does not cater for the concepts from an agent-based perspective. Here in this paper, we present a comprehensive multidisciplinary state-of-the-art review and taxonomy of game theory models of complex interactions between agents.
Breaking down banners: analytical approaches to determining the materials of painted banners
Authors: Smith M. J. , Thompson K. , Hermens E.
Published: July 2016

Background

This paper investigates a range of analytical techniques to yield information about the materials and processes used in making painted banners. A textile conservator, technical art historian and paintings conservator, and materials scientist have joined forces to develop a greater understanding of the potential of analytical findings in the identification of materials.

Results

Visual examination using low level magnification and microscopy proved to be a crucial starting point and for identification of areas for further analysis. High magnification microscopy of cross sections was invaluable to gather information regarding the build-up of the layers, their interaction and condition. Scanning electron microscopy (SEM) of ion-milled samples showed that different areas of the banner had been prepared in different ways. SEM-EDX (scanning electron microscopy energy-dispersive X-ray spectroscopy) confirmed the presence of the main elements of pigments. Raman enabled identification of specific pigments. Raman also provided confirmation of specific materials (such as the paint filler). Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) enabled the identification of oil and resin, confirmation of pigments and fibres. Thin layers made sampling and identification challenging. Presence of materials such as silk and lead white dominated some analysis making interpretation of other materials more difficult.

Conclusions

Sample preparation had a significant bearing on the effectiveness of the analysis. Ion-milling provided high quality surface on the cross section samples that enabled material interfaces to be clearly seen. The challenges of finding effective wavelengths for analysis of samples using Raman were clearly evident in this study. Microscopy showed fibres blends, easily missed using FTIR, whereas FTIR was particularly effective in the identification of man-made fibres. While portable instrumentation may be useful, for in-depth understanding of the heterogeneous layered materials sample taking still remains crucial. Commercial makers used many typical grounds and pigments but these were used sparingly, in thin layers, in order to produce a flexible object and also perhaps to reduce costs. The textile was however of high quality, in this case silk. Unexpectedly, the preparation layers do not appear to be consistent across the banner; the reasons for this need further investigation.
Allometric growth and development of organs in ballan wrasse (Labrus bergylta Ascanius, 1767) larvae in relation to different live prey diets and growth rates
Authors: Gagnat Maren Ranheim , Wold Per-Arvid , Bardal Tora , Øie Gunvor , Kjørsvik Elin
Published: July 2016

Small fish larvae grow allometrically, but little is known about how this growth pattern may be affected by different growth rates and early diet quality. The present study investigates how different growth rates, caused by start-feeding with copepods or rotifers the first 30 days post-hatch (dph), affect allometric growth and development of nine major organs in ballan wrasse (Labrus bergylta) larvae up to experimental end at 60 dph. Feeding with cultivated copepod nauplii led to both increased larval somatic growth and faster development and growth of organ systems than feeding with rotifers. Of the organs studied, the digestive and respiratory organs increased the most in size between 4 and 8 dph, having a daily specific growth rate (SGR) between 30 and 40% in larvae fed copepods compared with 20% or less for rotifer-fed larvae. Muscle growth was prioritised from flexion stage and onwards, with a daily SGR close to 30% between 21 and 33 dph regardless of treatment. All larvae demonstrated a positive linear correlation between larval standard length (SL) and increase in total tissue volume, and no difference in allometric growth pattern was found between the larval treatments. A change from positive allometric to isometric growth was observed at a SL close to 6.0 mm, a sign associated with the start of metamorphosis. This was also where the larvae reached postflexion stage, and was accompanied by a change in growth pattern for most of the major organ systems. The first sign of a developing hepatopancreas was, however, first observed in the largest larva (17.4 mm SL, 55 dph), indicating that the metamorphosis in ballan wrasse is a gradual process lasting from 6.0 to at least 15-17 mm SL.
Endogenous rhythm and pattern-generating circuit interactions in cockroach motor centres
Authors: David Izhak , Holmes Philip , Ayali Amir
Published: July 2016

Cockroaches are rapid and stable runners whose gaits emerge from the intricate, and not fully resolved, interplay between endogenous oscillatory pattern-generating networks and sensory feedback that shapes their rhythmic output. Here we studied the endogenous motor output of a brainless, deafferented preparation. We monitored the pilocarpine-induced rhythmic activity of levator and depressor motor neurons in the mesothoracic and metathoracic segments in order to reveal the oscillatory networks’ architecture and interactions. Data analyses included phase relations, latencies between and overlaps of rhythmic bursts, spike frequencies, and the dependence of these parameters on cycle frequency. We found that, overall, ipsilateral connections are stronger than contralateral ones. Our findings revealed asymmetries in connectivity among the different ganglia, in which meta-to-mesothoracic ascending coupling is stronger than meso-to-metathoracic descending coupling. Within-ganglion coupling between the metathoracic hemiganglia is stronger than that in the mesothoracic ganglion. We also report differences in the role and mode of operation of homologue network units (manifested by levator and depressor nerve activity). Many observed characteristics are similar to those exhibited by intact animals, suggesting a dominant role for feedforward control in cockroach locomotion. Based on these data we posit a connectivity scheme among components of the locomotion pattern generating system.
Loss of function of theDrosophilaNinein-related centrosomal protein Bsg25D causes mitotic defects and impairs embryonic development
Authors: Kowanda Michelle , Bergalet Julie , Wieczorek Michal , Brouhard Gary , Lécuyer Éric , Lasko Paul
Published: July 2016

The centrosome-associated proteins Ninein (Nin) and Ninein-like protein (Nlp) play significant roles in microtubule stability, nucleation and anchoring at the centrosome in mammalian cells. Here, we investigate Blastoderm specific gene 25D (Bsg25D), which encodes the only Drosophila protein that is closely related to Nin and Nlp. In early embryos, we find that Bsg25D mRNA and Bsg25D protein are closely associated with centrosomes and astral microtubules. We show that sequences within the coding region and 3′UTR of Bsg25D mRNAs are important for proper localization of this transcript in oogenesis and embryogenesis. Ectopic expression of eGFP-Bsg25D from an unlocalized mRNA disrupts microtubule polarity in mid-oogenesis and compromises the distribution of the axis polarity determinant Gurken. Using total internal reflection fluorescence microscopy, we show that an N-terminal fragment of Bsg25D can bind microtubules in vitro and can move along them, predominantly toward minus-ends. While flies homozygous for a Bsg25D null mutation are viable and fertile, 70% of embryos lacking maternal and zygotic Bsg25D do not hatch and exhibit chromosome segregation defects, as well as detachment of centrosomes from mitotic spindles. We conclude that Bsg25D is a centrosomal protein that, while dispensable for viability, nevertheless helps ensure the integrity of mitotic divisions in Drosophila.
Metabolomic approach for identifying and visualizing molecular tissue markers in tadpoles of Xenopus tropicalis by mass spectrometry imaging
Authors: Goto-Inoue Naoko , Kashiwagi Akihiko , Kashiwagi Keiko , Mori Tsukasa
Published: July 2016

In developmental and cell biology it is crucial to evaluate the dynamic profiles of metabolites. An emerging frog model system using Xenopus tropicalis, whose genome sequence and inbred strains are available, is now ready for metabolomics investigation in amphibians. In this study we applied matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) analysis to identify and visualize metabolomic molecular markers in tadpoles of Xenopus tropicalis. We detected tissue-specific peaks and visualized their distribution in tissues, and distinguished 19 tissues and their specific peaks. We identified, for the first time, some of their molecular localizations via tandem mass spectrometric analysis: hydrocortisone in artery, L-DOPA in rhombencephalon, taurine in eye, corticosterone in gill, heme in heart, inosine monophosphate and carnosine in muscle, dopamine in nerves, and phosphatidylethanolamine (16:0/20:4) in pharynx. This is the first MALDI-MSI study of X. tropicalis tadpoles, as in small tadpoles it is hard to distinguish and dissect the various organs. Furthermore, until now there has been no data about the metabolomic profile of each organ. Our results suggest that MALDI-MSI is potentially a powerful tool for examining the dynamics of metabolomics in metamorphosis as well as conformational changes due to metabolic changes.
Keratin impact on PKCδ- and ASMase-mediated regulation of hepatocyte lipid raft size – implication for FasR-associated apoptosis
Authors: Gilbert Stéphane , Loranger Anne , Omary M. Bishr , Marceau Normand
Published: July 2016

Keratins are epithelial cell intermediate filament (IF) proteins that are expressed as pairs in a cell-differentiation-regulated manner. Hepatocytes express the keratin 8 and 18 pair (denoted K8/K18) of IFs, and a loss of K8 or K18, as in K8-null mice, leads to degradation of the keratin partner. We have previously reported that a K8/K18 loss in hepatocytes leads to altered cell surface lipid raft distribution and more efficient Fas receptor (FasR, also known as TNFRSF6)-mediated apoptosis. We demonstrate here that the absence of K8 or transgenic expression of the K8 G62C mutant in mouse hepatocytes reduces lipid raft size. Mechanistically, we find that the lipid raft size is dependent on acid sphingomyelinase (ASMase, also known as SMPD1) enzyme activity, which is reduced in absence of K8/K18. Notably, the reduction of ASMase activity appears to be caused by a less efficient redistribution of surface membrane PKCδ toward lysosomes. Moreover, we delineate the lipid raft volume range that is required for an optimal FasR-mediated apoptosis. Hence, K8/K18-dependent PKCδ- and ASMase-mediated modulation of lipid raft size can explain the more prominent FasR-mediated signaling resulting from K8/K18 loss. The fine-tuning of ASMase-mediated regulation of lipid rafts might provide a therapeutic target for death-receptor-related liver diseases.
Drosophila Ringmaker regulates microtubule stabilization and axonal extension during embryonic development
Authors: Mino Rosa E. , Rogers Stephen L. , Risinger April L. , Rohena Cristina , Banerjee Swati , Bhat Manzoor A.
Published: July 2016

Axonal growth and targeting are fundamental to the organization of the nervous system, and require active engagement of the cytoskeleton. Polymerization and stabilization of axonal microtubules is central to axonal growth and maturation of neuronal connectivity. Studies have suggested that members of the tubulin polymerization promoting protein (TPPP, also known as P25α) family are involved in cellular process extension. However, no in vivo knockout data exists regarding its role in axonal growth during development. Here, we report the characterization of Ringmaker (Ringer; CG45057), the only Drosophila homolog of long p25α proteins. Immunohistochemical analyses indicate that Ringer expression is dynamically regulated in the embryonic central nervous system (CNS). ringer-null mutants show cell misplacement, and errors in axonal extension and targeting. Ultrastructural examination of ringer mutants revealed defective microtubule morphology and organization. Primary neuronal cultures of ringer mutants exhibit defective axonal extension, and Ringer expression in cells induced microtubule stabilization and bundling into rings. In vitro assays showed that Ringer directly affects tubulin, and promotes microtubule bundling and polymerization. Together, our studies uncover an essential function of Ringer in axonal extension and targeting through proper microtubule organization.
Divergence of structural strategies for homophilic E-cadherin binding among bilaterians
Authors: Nishiguchi Shigetaka , Yagi Akira , Sakai Nobuaki , Oda Hiroki
Published: July 2016

Homophilic binding of E-cadherins through their ectodomains is fundamental to epithelial cell–cell adhesion. Despite this, E-cadherin ectodomains have evolved differently in the vertebrate and insect lineages. Of the five rod-like, tandemly aligned extracellular cadherin domains of vertebrate E-cadherin, the tip extracellular cadherin domain plays a pivotal role in binding interactions. Comparatively, the six consecutive N-terminal extracellular cadherin domains of Drosophila E-cadherin, DE-cadherin (also known as Shotgun), can mediate adhesion; however, the underlying mechanism is unknown. Here, we report atomic force microscopy imaging of DE-cadherin extracellular cadherin domains. We identified a tightly folded globular structure formed by the four N-terminal-most extracellular cadherin domains stabilized by the subsequent two extracellular cadherin domains. Analysis of hybrid cadherins from different insects indicated that the E-cadherin globular portion is associated with determining homophilic binding specificity. The second to fourth extracellular cadherin domains were identified as the minimal portion capable of mediating exclusive homophilic binding specificity. Our findings suggest that the N-terminal-most four extracellular cadherin domains of insect E-cadherin are functionally comparable with the N-terminal-most single extracellular cadherin domain of vertebrate E-cadherin, but that their mechanisms might significantly differ. This work illuminates the divergence of structural strategies for E-cadherin homophilic binding among bilaterians.
Direct lentivirus injection for fast and efficient gene transfer into brown and beige adipose tissue
Authors: Balkow Aileen , S. Hoffmann Linda , Klepac Katarina , Glöde Anja , Gnad Thorsten , Zimmermann Katrin , Pfeifer Alexander
Published: July 2016

Brown adipose tissue is a special type of fat contributing to energy expenditure in human newborns and adults. Moreover, subcutaneous white adipose tissue has a high capacity to adapt an energy-consuming, brown-like/beige phenotype. Here, we developed an easy to handle and fast to accomplish method to efficiently transfer genes into brown and beige fat pads in vivo. Lentiviral vectors are directly injected into the target fat pad of anaesthetized mice through a small incision using a modified, small needle connected to a microsyringe, which is well suited for infiltration of adipose tissues. Expression of the target gene can be detected in brown/beige fat one week after injection. The method can be applied within minutes to efficiently deliver transgenes into subcutaneous adipose tissues. Thus, this protocol allows for studying genes of interest in a timely manner in murine brown/beige fat and could potentially lead to new gene therapies for obesity. Brown adipose tissue is a special type of fat contributing to energy expenditure in human newborns and adults. Moreover, subcutaneous white adipose tissue has a high capacity to adapt an energy-consuming, brown-like/beige phenotype. Here, we developed an easy to handle and fast to accomplish method to efficiently transfer genes into brown and beige fat pads in vivo. Lentiviral vectors are directly injected into the target fat pad of anaesthetized mice through a small incision using a modified, small needle connected to a microsyringe, which is well suited for infiltration of adipose tissues. Expression of the target gene can be detected in brown/beige fat one week after injection. The method can be applied within minutes to efficiently deliver transgenes into subcutaneous adipose tissues. Thus, this protocol allows for studying genes of interest in a timely manner in murine brown/beige fat and could potentially lead to new gene therapies for obesity.
Results of Sentinel Lymph Node Biopsy in Patients with Breast Cancer in 10-Year Own Material of the 4th Military Teaching Hospital with Polyclinic in Wrocław
Authors: Kabziński Piotr , Rac Jacek , Dorobisz Tadeusz , Pawłowski Wiktor , Ziomek Agnieszka , Chabowski Mariusz , Janczak Dawid , Leśniak Michał , Janczak Dariusz
Published: July 2016

At present, sentinel lymph node biopsy is a standard procedure to assess the advancement of breast cancer and cutaneous melanoma.

The aim of the study was to assess the role of the sentinel lymph node biopsy in the treatment of patients with breast cancer in our own material.

Material and methods. Analyzed was medical documentation of 258 patients with initially operable breast cancer, qualified for operation with sentinel lymph node biopsy in 2004-2014 in the Department of Surgery of the 4

Results. On the basis of the gathered material, obtained were the following parameters: sensitivity - 100%, and specificity - 94.6%. Four cases were false negative (5.5%).

Conclusions. 1. Marking the sentinel lymph node in breast cancer, based on the single visualisation method with the use of radioisotope, is a useful and effective technique. 2. The factor influencing the results of the sentinel lymph node biopsy (true positive and negative results and false negative result) was the number of the excised lymph nodes except for the sentinel lymph node. 3. Patients with estrogen receptor expression had often metastases to sentinel lymph node (145 cases - 56%). 4. The false negative rate, i.e. 5.5% in our material, is within the limits of acceptability given in the literature. 5. The sentinel lymph node biopsy performed by the experienced surgical team is a reliable diagnostic tool with a low complication rate.
Comparison of robust estimators for leveling networks in Monte Carlo simulations
Authors: Pokarowska Maria
Published: July 2016

We compared the method of least squares (LS), Pope’s iterative data snooping (IDS) and Huber’s M-estimator (HU) in realistic leveling networks, for which the heights or the vertical displacements of points are known. The study was conducted using the Monte Carlo simulation, in which one repeatedly generates sets of observations related to the measurement data, then calculates values of the estimators and, finally, assesses it with respect to the real coordinates. To simulate outliers we used popular mixture models with two or more normal distributions. It is shown that for small, strong networks robust methods IDS and HU are more accurate than LS, but for large, weak networks occurring in practice there is no significant difference between the considered methods in the accuracy of the solution.
Soil sealing degree as factor influencing urban soil contamination with polycyclic aromatic hydrocarbons (PAHs)
Authors: Mendyk Łukasz , Charzyński Przemysław
Published: July 2016

The objective of the study was to determine role of soil sealing degree as the factor influencing soil contamination with polycyclic aromatic hydrocarbons (PAHs). The study area included four sampling sites located within the administrative boundaries of the Toruń city, Poland. Sampling procedure involved preparing soil pits representing three examples of soil sealing at each site: non-sealed soil as a control one (I) and two degrees of soil sealing: semi-pervious surface (II) and totally impervious surface (III). Together with basic properties defined with standard procedures (particle size distribution, pH, LOI, content of carbonates) content of selected PAHs was determined by dichloromethane extraction using gas chromatography with mass spectrometric detection (GC-MS). Obtained results show that urban soils in the city of Toruń are contaminated with polycyclic aromatic hydrocarbons. Soil sealing degree has a strong influence on the soil contamination with polycyclic aromatic hydrocarbons. Totally sealed soils are better preserved from atmospheric pollution including PAHs. Combustion of grass/wood/coal was the main source of determined PAHs content in examined soils.
Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria
Authors: Noctor Eoin , Crowe Catherine , Carmody Louise A , Saunders Jean A , Kirwan Breda , O’Dea Angela , Gillespie Paddy , Glynn Liam G , McGuire Brian E , O’Neill Ciarán , O’Shea P M , Dunne F P , _ _
Published: July 2016

Objective

An increase in gestational diabetes mellitus (GDM) prevalence has been demonstrated across many countries with adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. Here, we determine the cumulative incidence of abnormal glucose tolerance among women with previous GDM, and identify clinical risk factors predicting this.

Design

Two hundred and seventy women with previous IADPSG-defined GDM were prospectively followed up for 5years (mean 2.6) post-index pregnancy, and compared with 388 women with normal glucose tolerance (NGT) in pregnancy.

Methods

Cumulative incidence of abnormal glucose tolerance (using American Diabetes Association criteria for impaired fasting glucose, impaired glucose tolerance and diabetes) was determined using the Kaplan–Meier method of survival analysis. Cox regression models were constructed to test for factors predicting abnormal glucose tolerance.

Results

Twenty-six percent of women with previous GDM had abnormal glucose tolerance vs 4% with NGT, with the log-rank test demonstrating significantly different survival curves (P<0.001). Women meeting IADPSG, but not the World Health Organization (WHO) 1999 criteria, had a lower cumulative incidence than women meeting both sets of criteria, both in the early post-partum period (4.2% vs 21.7%, P<0.001) and at longer-term follow-up (13.7% vs 32.6%, P<0.001). Predictive factors were glucose levels on the pregnancy oral glucose tolerance test, family history of diabetes, gestational week at testing, and BMI at follow-up.

Conclusions

The proportion of women developing abnormal glucose tolerance remains high among those with IADPSG-defined GDM. This demonstrates the need for continued close follow-up, although the optimal frequency and method needs further study.
TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells
Authors: Palladino Giuseppe , Notarangelo Tiziana , Pannone Giuseppe , Piscazzi Annamaria , Lamacchia Olga , Sisinni Lorenza , Spagnoletti Girolamo , Toti Paolo , Santoro Angela , Storto Giovanni , Bufo Pantaleo , Cignarelli Mauro , Esposito Franca , Landriscina Matteo
Published: July 2016

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role in thyroid carcinoma (TC), still unaddressed at present, was investigated by analyzing its expression in a cohort of 86 human TCs and evaluating its involvement in cancer cell survival and proliferationin vitro. Indeed, TRAP1 levels progressively increased from normal peritumoral thyroid gland, to papillary TCs (PTCs), follicular variants of PTCs (FV-PTCs) and poorly differentiated TCs (PDTCs). By contrast, anaplastic thyroid tumors exhibited a dual pattern, the majority being characterized by high TRAP1 levels, while a small subgroup completely negative. Consistently with a potential involvement of TRAP1 in thyroid carcinogenesis, TRAP1 silencing resulted in increased sensitivity to paclitaxel-induced apoptosis, inhibition of cell cycle progression and attenuation of ERK signaling. Noteworthy, the inhibition of TRAP1 ATPase activity by pharmacological agents resulted in attenuation of cell proliferation, inhibition of ERK signaling and reversion of drug resistance. These data suggest that TRAP1 inhibition may be regarded as potential strategy to target specific features of human TCs, i.e., cell proliferation and resistance to apoptosis.
Current status and future perspectives: TSPO in steroid neuroendocrinology
Authors: Selvaraj Vimal , Tu Lan N
Published: July 2016

The mitochondrial translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), has received significant attention both as a diagnostic biomarker and as a therapeutic target for different neuronal disease pathologies. Recently, its functional basis believed to be mediating mitochondrial cholesterol import for steroid hormone production has been refuted by studies examining bothin vivoandin vitrogeneticTspo-deficient models. As a result, there now exists a fundamental gap in the understanding of TSPO function in the nervous system, and its putative pharmacology in neurosteroid production. In this review, we discuss several recent findings in steroidogenic cells that are in direct contradiction to previous studies, and necessitate a re-examination of the purported role for TSPO inde novoneurosteroid biosynthesis. We critically examine the pharmacological effects of different TSPO-binding drugs with particular focus on studies that measure neurosteroid levels. We highlight the basis of key misconceptions regarding TSPO that continue to pervade the literature, and the need for interpretation with caution to avoid negative impacts. We also summarize the emerging perspectives that point to new directions that need to be investigated for understanding the molecular function of TSPO, only after which the true potential of this therapeutic target in medicine may be realized.
A matter of style
Authors: Oliva Miguel A. Aijón , Serrano María José
Published: July 2016

The construction of sex/gender as a dynamic set of values in communicative interaction is a matter of ever growing interest, superseding traditional approaches based on socio-structural and/or biological factors. The purpose of this paper is to investigate the relationship between the statistical patterning of linguistic choices across genders and the meaningful use of such elements in particular contexts. The main hypothesis is that large-scale patterns of variation are tightly connected to the dynamics of specific interaction: speakers are to some extent aware of the typical association of linguistic variants with social groups and interactional domains. In turn, their creative stylistic choices can help maintain or alter such associations. The variable expression of several Spanish subject pronouns is quantitatively and qualitatively analysed. The results indicate that male discourse usually shows higher rates of expressed subject pronouns, while women are more inclined to omission. But there are also differences in their respective preference for particular grammatical subjects, with men promoting the use of the singular first person and women that of the second one. A relationship is suggested between gendered styles and the discursive–cognitive continuum from objectivity to subjectivity, this being projected on a wide range of communicative possibilities.