bluuebunny/crossref_metadata_2025 huggingface dataset:
miR‐149 controls non‐alcoholic fatty liver by targeting FGF‐21
Authors: Xiao Junjie , Lv Dongchao , Zhao Yingying , Chen Xiaoyu , Song Meiyi , Liu Jingqi , Bei Yihua , Wang Fei , Yang Wenzhuo , Yang Changqing
Published: April 2016

Non‐alcoholic fatty liver disease (NAFLD), a lipid metabolism disorder characterized by the accumulation of intrahepatic fat, has emerged as a global public health problem. However, its underlying molecular mechanism remains unclear. We previously have found that miR‐149 was elevated in NAFLD induced by high‐fat diet mice model, whereas decreased by a 16‐week running programme. Here, we reported that miR‐149 was increased in HepG2 cells treated with long‐chain fatty acid (FFA). In addition, miR‐149 was able to promote lipogenesis in HepG2 cells in the absence of FFA treatment. Moreover, inhibition of miR‐149 was capable of inhibiting lipogenesis in HepG2 cells in the presence of FFA treatment. Meanwhile, fibroblast growth factor‐21 (FGF‐21) was identified as a target gene of miR‐149, which was demonstrated by the fact that miR‐149 could negatively regulate the protein expression level of FGF‐21, and FGF‐21 was also responsible for the effect of miR‐149 inhibitor in decreasing lipogenesis in HepG2 cells in the presence of FFA treatment. These data implicate that miR‐149 might be a novel therapeutic target for NAFLD.
Minocycline attenuates post‐operative cognitive impairment in aged mice by inhibiting microglia activation
Authors: Wang Hui‐Lin , Liu Hua , Xue Zhang‐Gang , Liao Qing‐Wu , Fang Hao
Published: April 2016

Although it is known that isoflurane exposure or surgery leads to post‐operative cognitive dysfunction in aged rodents, there are few clinical interventions and treatments available to prevent this disorder. Minocycline (MINO) produces neuroprotection from several neurodegenerative diseases and various experimental animal models. Therefore, we set out to investigate the effects of MINO pre‐treatment on isoflurane or surgery induced cognitive impairment in aged mice by assessing the hippocampal‐dependent spatial memory performance using the Morris water maze task. Hippocampal tissues were isolated from mice and evaluated by Western blot analysis, immunofluorescence procedures and protein array system. Our results elucidate that MINO down‐regulated the isoflurane‐induced and surgery‐induced enhancement in the protein levels of pro‐inflammatory cytokine tumour necrosis factor alpha, interleukin (IL)‐1β, interferon‐γ and microglia marker Iba‐1, and up‐regulated protein levels of the anti‐inflammatory cytokine IL‐4 and IL‐10. These findings suggest that pre‐treatment with MINO attenuated isoflurane or surgery induced cognitive impairment by inhibiting the overactivation of microglia in aged mice.
The EU Convergence Machine at Work. To the Benefit of the EU's Poorest Citizens?
Authors: Goedemé Tim , Collado Diego
Published: April 2016

Social cohesion in the EU (European Union) is usually assessed on the basis of GDP per capita and relative poverty rates. These indicators show that the ‘European convergence machine’ led to greater social cohesion between old and new Member States (EU‐15 and NMS) until the onset of the crisis. In this article we offer an alternative perspective by directly comparing EU citizens’ disposable household incomes. Using four waves of EU‐SILC data, we explore what happened between 2005 and 2011 in the EU‐15 and NMS regarding changes in the lowest household incomes in relation to the EU‐wide median. Results show that, overall, the convergence machine seemed to work well for the lowest incomes in the NMS, but not so much for those living in the EU‐15. At the same time, differences in living standards remain quite large. This points to important continued challenges for EU policy initiatives in the social domain.
Deposition of elafin in the involved vascular wall of neutrophil‐mediated cutaneous vasculitis
Authors: Muto J. , Fujimoto N. , Ono K. , Kobayashi T. , Chen K.R. , Suzuki S. , Wachi H. , Tajima S.
Published: April 2016

Background

Neutrophil elastase plays an important role in skin inflammation induced by neutrophil infiltration. Elafin is an inducible elastase inhibitor expressed by keratinocytes, and is known to be involved in pathogenesis of neutrophilic skin disorders such as psoriasis.

Methods

Immunohistochemical studies of elafin expression in the cases of vasculitis were performed. Induction of elafin expression in cultured vascular cells and its effect on neutrophil migration were studied in vitro.

Results

A positive immunoreactivity was detected in polyarteritis nodosa, giant cell arteritis and Schönlein–Henoch purpura, but no immunoreactivity was found in Churg–Strauss syndrome. Elafin expression in cultured venous endothelial cells and arterial smooth muscle cells was undetectable, but induced by interleukin‐1β (IL‐1β) and IL‐8. Elafin inhibited the elastin peptide‐induced neutrophil chemotaxis at the concentration of 10−8–10−5 mol/L.

Conclusion

Elafin deposition induced by cytokines (IL‐1β or IL‐8) will be an important regulator for the progress of leucocytoclastic vasculitis by functioning as an inhibitor for neutrophil chemotaxis as well as for vascular elastin degradation.
Beyond animals and plants: dynamic maternal effects in the fungusNeurospora crassa
Authors: Zimmerman K. C. K. , Levitis D. A. , Pringle A.
Published: April 2016

Maternal effects are widely documented in animals and plants, but not in fungi or other eukaryotes. A principal cause of maternal effects is asymmetrical parental investment in a zygote, creating greater maternal vs. paternal influence on offspring phenotypes. Asymmetrical investments are not limited to animals and plants, but are also prevalent in fungi and groups including apicomplexans, dinoflagellates and red algae. Evidence suggesting maternal effects among fungi is sparse and anecdotal. In an experiment designed to test for maternal effects across sexual reproduction in the model fungusNeurospora crassa, we measured offspring phenotypes from crosses of all possible pairs of 22 individuals. Crosses encompassed reciprocals of 11 mating‐type ‘A’ and 11 mating‐type ‘a’ wild strains. After controlling for the genetic and geographic distances between strains in any individual cross, we found strong evidence for maternal control of perithecia (sporocarp) production, as well as maternal effects on spore numbers and spore germination. However, both parents exert equal influence on the percentage of spores that are pigmented and size of pigmented spores. We propose a model linking the stage‐specific presence or absence of maternal effects to cellular developmental processes: effects appear to be mediated primarily through the maternal cytoplasm, and, after spore cell walls form, maternal influence on spore development is limited. Maternal effects in fungi, thus far largely ignored, are likely to shape species' evolution and ecologies. Moreover, the association of anisogamy and maternal effects in a fungus suggests maternal effects may also influence the biology of other anisogamous eukaryotes.
People‐centred health systems, a bottom‐up approach: where theory meets empery
Authors: Sturmberg Joachim P , Njoroge Alice
Published: April 2016

Background and methods

Health systems are complex and constantly adapt to changing demands. These complex‐adaptive characteristics are rarely considered in the current bureaucratic top‐down approaches to health system reforms aimed to constrain demand and expenditure growth. The economic focus fails to address the needs of patients, providers and communities, and ultimately results in declining effectiveness and efficiency of the health care system as well as the health of the wider community. A needs‐focused complex‐adaptive health system can be represented by the ‘healthcare vortex’ model; how to build a needs‐focused complex‐adaptive health system is illustrated by Eastern Deanery AIDS Relief Program approaches in the poor neighbourhoods of Nairobi, Kenya.

Findings and conclusions

A small group of nurses and community health workers focused on the care of terminally ill HIV/AIDS patients. This work identified additional problems: tuberculosis (TB) was underdiagnosed and undertreated, a local TB‐technician was trained to run a local lab, a courier services helped to reach all at need, collaboration with the Ministry of Health established local TB and HIV treatment programmes and philanthropists helped to supplement treatment with nutrition support. Maternal‐to‐child HIV‐prevention and adolescent counselling services addressed additional needs.

The ‘theory of the healthcare vortex’ indeed matches the ‘empery of the real world experiences’. Locally developed and delivered adaptive, people‐centred health systems, a bottom‐up community and provider initiated approach, deliver highly effective and sustainable health care despite significant resource constraints.
Influence of Color Education and Training on Shade Matching Skills
Authors: Ristic Ivan , Stankovic Sasa , Paravina Rade D
Published: April 2016

Objectives

To evaluate the influence of education and training on quality of tooth color matching.

Material and Methods

Dental students (N = 174), matched the color of eight shade tabs in a viewing booth, using VITA Linearguide 3D‐Master shade guide. The experimental group had color education and training between the before and after session. The control group did not have any additional information in between two sessions. Color differences between the task tabs and selected tabs were calculated using CIE formulas. The score for the best match (smallest color difference) was 10 points, the 2nd best match 9 points, down to 1 point for the 10th best match. Means and standard deviations were calculated. Differences were analyzed using the Student t‐test.

Results

Shade matching scores in the experimental group were significantly better after education and training (p < 0.001), with a mean score before and after shade matching sessions of 7.06 (1.19) and 8.43 (0.92), respectively. The percentage of students in the experimental group that selected one of three best matches increased 24.3%. The control group exhibited no significant improvement in the after session.

Conclusions

Within the limitations of the study, education and training improved students’ shade matching skills.

Clinical Significance

While the vast majority of dental restorations and practically all restorations in the esthetic zone are tooth colored, the profession as a whole is far from perfect when it comes to accurate shade matching. Education and training can improve shade matching ability: enhanced esthetics of dental restorations, increased patient satisfaction, and a reduced number of color corrections are some of the notable benefits and rewards. (J Esthet Restor Dent 00:000–000, 2016) J Esthet Restor Dent 28:287–294, 2016)
Trachyrhizium urniformis n. g., n. sp., a Novel Marine Filose Thecate Amoeba Related to a Cercozoan Environmental Clade (Novel Clade 4)
Authors: Shiratori Takashi , Ishida Ken‐ichiro
Published: April 2016

A novel cercozoan filose thecate amoeba, Trachyrhizium urniformis n. g., n. sp., was isolated from a marine sediment sample collected at Agenashiku Island, Okinawa, Japan. We performed light and electron microscopic observations, and a molecular phylogenetic analysis using the small subunit ribosomal RNA gene of the isolate. Cells of T. urniformis are spherical in shape and are covered by a thin theca possessing a wide rounded aperture. Branching and occasionally anastomosing filopodia with small granules emerge from the aperture. The granules are transported in the filopodia bidirectionally. Transmission electron microscopy showed that cells of T. urniformis possess nucleus with permanently condensed chromatin, Golgi apparatuses, microbodies, mitochondria with tubular cristae, and extrusomes. Several morphological and ultrastructural features of T. urniformis (the presence of thecae and nucleus with permanently condensed chromatin) show similarities with those of Thecofilosea. In a phylogenetic analysis, T. urniformis included in Thecofilosea with weak statistical supports and formed a clade with two sequences that constitutes a cercozoan environmental clade, novel clade 4. On the basis of morphological and ultrastructural information and the results of the phylogenetic analysis, we propose T. urniformis as a new member of class Thecofilosea.
Next‐Generation Sequencing Assessment of Eukaryotic Diversity in Oil Sands Tailings Ponds Sediments and Surface Water
Authors: Aguilar Maria , Richardson Elisabeth , Tan BoonFei , Walker Giselle , Dunfield Peter F. , Bass David , Nesbø Camilla , Foght Julia , Dacks Joel B.
Published: April 2016

Tailings ponds in the Athabasca oil sands (Canada) contain fluid wastes, generated by the extraction of bitumen from oil sands ores. Although the autochthonous prokaryotic communities have been relatively well characterized, almost nothing is known about microbial eukaryotes living in the anoxic soft sediments of tailings ponds or in the thin oxic layer of water that covers them. We carried out the first next‐generation sequencing study of microbial eukaryotic diversity in oil sands tailings ponds. In metagenomes prepared from tailings sediment and surface water, we detected very low numbers of sequences encoding eukaryotic small subunit ribosomal RNA representing seven major taxonomic groups of protists. We also produced and analysed three amplicon‐based 18S rRNA libraries prepared from sediment samples. These revealed a more diverse set of taxa, 169 different OTUs encompassing up to eleven higher order groups of eukaryotes, according to detailed classification using homology searching and phylogenetic methods. The 10 most abundant OTUs accounted for > 90% of the total of reads, vs. large numbers of rare OTUs (< 1% abundance). Despite the anoxic and hydrocarbon‐enriched nature of the environment, the tailings ponds harbour complex communities of microbial eukaryotes indicating that these organisms should be taken into account when studying the microbiology of the oil sands.
Temporal and spatial trends in prey composition of wahoo Acanthocybium solandri: a diet analysis from the central North Pacific Ocean using visual and DNA bar‐coding techniques
Authors: Oyafuso Z. S. , Toonen R. J. , Franklin E. C.
Published: April 2016

A diet analysis was conducted on 444 wahoo Acanthocybium solandri caught in the central North Pacific Ocean longline fishery and a nearshore troll fishery surrounding the Hawaiian Islands from June to December 2014. In addition to traditional observational methods of stomach contents, a DNA bar‐coding approach was integrated into the analysis by sequencing the cytochrome c oxidase subunit 1 (COI) region of the mtDNA genome to taxonomically identify individual prey items that could not be classified visually to species. For nearshore‐caught A. solandri, juvenile pre‐settlement reef fish species from various families dominated the prey composition during the summer months, followed primarily by Carangidae in autumn months. Gempylidae, Echeneidae and Scombridae were dominant prey taxa from the offshore fishery. Molidae was a common prey family found in stomachs collected north‐east of the Hawaiian Archipelago while tetraodontiform reef fishes, known to have extended pelagic stages, were prominent prey items south‐west of the Hawaiian Islands. The diet composition of A. solandri was indicative of an adaptive feeder and thus revealed dominant geographic and seasonal abundances of certain taxa from various ecosystems in the marine environment. The addition of molecular bar‐coding to the traditional visual method of prey identifications allowed for a more comprehensive range of the prey field of A. solandri to be identified and should be used as a standard component in future diet studies.
Quality, Textural, and Sensory Properties of Yellow Alkaline Noodles Formulated with Salted Duck Egg White
Authors: Tan Thuan‐Chew , Phatthanawiboon Tanyong , Mat Easa Azhar
Published: April 2016

The objective of this study was to utilize salted duck egg white as an alternative source of salt for yellow alkaline noodles (YAN). YAN with salted duck egg white (YAN‐EW) was formulated by incorporating 15.21 g of salted duck egg white to replace the 1 g of salt. The effects of this substitution on the proximate compositions, physicochemical properties, cooking properties, textural properties and organoleptic properties of YAN were determined. YAN‐EW showed to have significantly higher (P < 0.05) protein content, lighter and more yellowish compared to control YAN‐C. No significant difference between YAN‐EW and YAN‐C in terms of pH and cooking properties. YAN‐EW exhibited similar hardness and springiness as YAN‐C, but have significantly higher (P < 0.05) cohesiveness and chewiness. YAN‐EW received scores on a par with YAN‐C in all sensory attributes. All the sensory attributes scored higher than 5, indicating good acceptance of YAN‐EW by the sensory panelists.

Practical Applications

High demand on traditional Chinese foods, such as mooncakes and glutinous rice dumplings, generated a large amount of waste, i.e., salted duck egg white. Potential use of salted duck egg white as a food ingredient is of great interest to the industry. The present work describes the use of salted duck egg white in yellow alkaline noodle. The main finding is that salted duck egg white showed potential to be utilized as an alternative source to table salt in noodle formulation. This information can be useful to noodle producers in utilizing “waste” as a natural source of salt.
Influence of sewer network models on urban flood damage assessment based on coupled 1D/2D models
Authors: Martins R. , Leandro J. , Djordjević S.
Published: April 2016

One of the main steps in assessing flood risk in urbanised areas is the quantification of damage costs. Damage is often estimated based on depth‐damage curves for which depth maps are obtained (ideally) from coupled flood models. While the comparative analysis of flood damage models has been extensively researched in the literature, the influence of the underlying sewer network model has not been investigated. In this study, a 2D locally inertial equations flood risk analysis model (GWM) is coupled with two stormwater models (SWMM, tested with three different configurations, and SIPSON). The assessment of the network performance is made through the total exchanged volume between the surface and stormwater system, the surcharged conduits and manholes, maximum overland inundation and costs using a stepped version of the multi‐coloured manual depth‐damage curves for continuous urban fabric. The models behave similarly; however, they do show differences in the head pressures, number of surcharged manholes and maximum depth in some locations. The case study results show that despite the good agreement in damage between the four configurations (≈6% maximum disagreement), some localised high differences in maximum depth observed [0.25 (m)] exist. It was also shown that
SWMM
needs to be calibrated in order to perform similarly to Preissmann slot models.
Flood vulnerability assessment in the mountain–plateau transition zone: a case study of Marginea village (Romania)
Authors: Romanescu G. , Hapciuc O.E. , Minea I. , Iosub M.
Published: April 2016

The Sucevita catchment is affected by heavy rains, which produce annual floods with catastrophic effects. Among them, the material damages caused to the dwellings of Marginea village stand out. The present study examines the vulnerability of the population and buildings of a village situated in the eastern part of the Eastern Carpathians. By applying the multicriteria method, areas with high flood vulnerability were pointed out in the Sucevita catchment. Hydraulic modelling was carried out using the HEC‐RAS software and revealed that 58 dwellings with high vulnerability will be affected in the case of a flood with an exceedance probability of 1% and 17 buildings in the case of a flood with an exceedance probability of 5%. By knowing the flood vulnerability zones, the appropriate measures can reduce the damages of a hydrological event. Moreover, the proper delimitation of the floodplain leads to adequate economic management and ensures the security of the population.
Extended‐Spectrum Β‐Lactamase and Plasmid‐Mediated AMPC Genes in Swine and Ground Pork
Authors: Sabia Carla , Stefani Sara , Messi Patrizia , de Niederhäusern Simona , Bondi Moreno , Condò Carla , Iseppi Ramona , Anacarso Immacolata
Published: April 2016

We investigated the presence of ESBL and AmpC‐producing Enterobacteriaceae isolated from 200 rectal swabs of healthy swine and 200 samples of ground pork. Phenotypic testing by using the double synergy differential test (DSDT) for ESBL/AmpC‐positive strains was confirmed by PCR and DNA sequence analysis. The localization of beta‐lactamase genes was established by conjugation experiments. ESBL and/or AmpC‐producing Enterobacteriaceae was found in 52.2% (95/182) of the isolates collected from rectal swabs and 3% (3/100) of isolates obtained from ground pork samples. Polymerase chain reaction and sequencing confirmed the presence of blaTEM‐20, blaTEM‐34, blaTEM‐52, blaCTX‐M‐1, blaSHV‐12, blaTEM‐1+SHV‐12, blaTEM‐20+SHV‐12, blaCMY‐2, blaTEM‐1+ CMY‐2, blaACC‐1 and blaACC‐2. The conjugation assays yielded positive results, denoting a plasmid localization of the genes.

Practical Applications

In this study, the prevalence of ESBL and AmpC‐producing Enterobacteriaceae isolated from rectal swabs of healthy swine and samples of ground pork were determined. ESBL/AmpC‐positive strains were confirmed by PCR and DNA sequence analysis. The most frequently isolated species was E.coli, among the most common variants detected TEM‐type ESBL, TEM‐52 was showed. These findings provide new information about the presence of ESBL/AmpC at the farm level and have important implications for assessments of risks of meat contamination during slaughter.
Long‐term pain relief with optimized medical treatment including antioxidants and step‐up interventional therapy in patients with chronic pancreatitis
Authors: Shalimar  , Midha Shallu , Hasan Ajmal , Dhingra Rajan , Garg Pramod Kumar
Published: April 2016

Background and aim

Abdominal pain is difficult to treat in patients with chronic pancreatitis (CP). Medical therapy including antioxidants has been shown to relieve pain of CP in the short‐term. Our aim was to study the long‐term results of optimized medical and interventional therapy for pain relief in patients with CP with a step‐up approach.

Methods

All consecutive patients with CP were included prospectively in the study. They were treated medically with a well‐balanced diet, pancreatic enzymes, and antioxidants (9000 IU beta‐carotene, 0.54 g vitamin C, 270 IU vitamin E, 600 µg organic selenium, and 2 g methionine). Endoscopic therapy and/or surgery were offered if medical therapy failed. Pain relief was the primary outcome measure.

Results

A total of 313 patients (mean age 26.16 ± 12.17; 244 males) with CP were included; 288 (92%) patients had abdominal pain. The etiology of CP was idiopathic in 224 (71.6%) and alcohol in 82 (26.2%). At 1‐year follow‐up, significant pain relief was achieved in 84.7% of patients: 52.1% with medical therapy, 16.7% with endoscopic therapy, 7.6% with surgery, and 8.3% spontaneously. The mean pain score decreased from 6.36 ± 1.92 to 1.62 ± 2.10 (P < 0.001). Of the 288 patients, 261, 218, 112, and 51 patients were followed up for 3, 5, 10, and 15 years, respectively; 54.0%, 57.3%, 60.7%, and 68.8% of them became pain free at those follow‐up periods.

Conclusion

Significant pain relief is achieved in the majority of patients with optimized medical and interventional treatment.
Exosome in intestinal mucosal immunity
Authors: Xu An Tao , Lu Jun Tao , Ran Zhi Hua , Zheng Qing
Published: April 2016

Intercellular communication of immune cells is critical to elicit efficient inflammatory responses. In intestinal mucosa, imbalance in pro‐inflammatory and anti‐inflammatory mediators, especially cytokines and chemokines, characterizes the underlying immune mechanisms of inflammatory bowel disease. Exosomes, small membrane vesicles secreted into the extracellular environment, are emerging as another important intercellular messenger in immune responses. A major recent breakthrough in this field unveils the capacity of exosomes to mediate the functional transfer of genetic materials (mRNAs and miRNAs) between immune cells. RAB27A and RAB27B are two small GTPases involved in exosome secretion. With respect to intestinal mucosal immunity, increased number of RAB27A‐positive immune cells and RAB27B‐positive immune cells are demonstrated in the colonic mucosa of patients with active ulcerative colitis as compared with that of healthy controls. This indicates the important role of exosome‐mediated immune responses in the pathogenesis of inflammatory bowel disease. Here, we will discuss the immune properties of exosomes and recent advances in their function with a special focus on intestinal mucosal immunity.
Geriatric Syndromes in Hospitalized Older Adults Discharged to Skilled Nursing Facilities
Authors: Bell Susan P. , Vasilevskis Eduard E. , Saraf Avantika A. , Jacobsen J. M. L. , Kripalani Sunil , Mixon Amanda S. , Schnelle John F. , Simmons Sandra F.
Published: April 2016

Objectives

To determine the prevalence, recognition, co‐occurrence, and recent onset of geriatric syndromes in individuals transferred from the hospital to a skilled nursing facility (SNF).

Design

Quality improvement project.

Setting

Acute care academic medical center and 23 regional partner SNFs.

Participants

Medicare beneficiaries hospitalized between January 2013 and April 2014 and referred to SNFs (N = 686).

Measurements

Project staff measured nine geriatric syndromes: weight loss, lack of appetite, incontinence, and pain (standardized interview); depression (Geriatric Depression Scale); delirium (Brief Confusion Assessment Method); cognitive impairment (Brief Interview for Mental Status); and falls and pressure ulcers (hospital medical record using hospital‐implemented screening tools). Estimated prevalence, new‐onset prevalence, and common coexisting clusters were determined. The extent to which treating physicians commonly recognized syndromes and communicated them to SNFs in hospital discharge documentation was evaluated.

Results

Geriatric syndromes were prevalent in more than 90% of hospitalized adults referred to SNFs; 55% met criteria for three or more coexisting syndromes. The most‐prevalent syndromes were falls (39%), incontinence (39%), loss of appetite (37%), and weight loss (33%). In individuals who met criteria for three or more syndromes, the most common triad clusters were nutritional syndromes (weight loss, loss of appetite), incontinence, and depression. Treating hospital physicians commonly did not recognize and document geriatric syndromes in discharge summaries, missing 33% to 95% of syndromes present according to research personnel.

Conclusion

Geriatric syndromes in hospitalized older adults transferred to SNFs are prevalent and commonly coexist, with the most frequent clusters including nutritional syndromes, depression, and incontinence. Despite the high prevalence, this clinical information is rarely communicated to SNFs on discharge.
Effects of Self‐Management Groups for People with Dementia and Their Spouses—Randomized Controlled Trial
Authors: Laakkonen Marja‐Liisa , Kautiainen Hannu , Hölttä Eeva , Savikko Niina , Tilvis Reijo S. , Strandberg Timo E. , Pitkälä Kaisu H.
Published: April 2016

Objectives

To investigate the effect of self‐management group rehabilitation for persons with dementia (PwD) and their spouses on their health‐related quality of life (HRQoL), the cognition of the PwD, and the costs of health and social services.

Design

A randomized controlled trial.

Setting

Primary care and memory clinics in the Helsinki metropolitan area, Finland.

Participants

PwD (N = 136) and their spouses (N = 136).

Intervention

Couples were randomized to usual care or eight‐session self‐management groups for PwD and concurrently for their spouses. Sessions aim to enhance self‐efficacy and problem‐solving skills and to provide peer support.

Measurements

The primary outcome measures were the HRQoL of PwD (measured using a generic, comprehensive (15‐dimensional), self‐administered instrument (15D)) and spouses (measured using the RAND‐36) and the spousal Sense of Competence Questionnaire (SCQ). Secondary outcome measures were PwD cognition (Verbal Fluency (VF), Clock Drawing Test (CDT)) and costs of health and social services during 24 months.

Results

At 3 months, the spouse physical component of the RAND‐36 improved (mean change 1.0, 95% confidence interval (CI) = −0.5 to 2.4) for those undergoing the intervention and worsened for controls (mean change −2.0, 95% CI = −3.5 to −0.4) (P = .006 adjusted for age, sex, baseline value of the physical component of the RAND‐36). There were no differences between the groups on the mental component of the RAND‐36, the SCQ, or the 15D. At 9 months, PwD change in VF was −0.38 (95% CI = −1.03 to 0.27) in intervention group and −1.60 (95% CI = −2.26 to −0.94) for controls (P = .011 adjusted for age, sex, baseline MMSE score). CDT changes were similar to VF changes. Differences in incremental costs between the groups was −436 € per person per year (95% CI = −4,986 to 4,115) for PwD (P = .35 adjusted for age, CDR) and −896 € per person per year (95% CI = −3,657 to 1,864) for spouses (P = .51 adjusted for PwD age, CDR).

Conclusions

The intervention had beneficial effects on the HRQoL of spouses and the cognitive function of PwD without increasing total costs. Trial registration: anzctr.org.au Identifier: ACTRN12611001173987.
Effect of Hospice Use on Costs of Care for Long‐Stay Nursing Home Decedents
Authors: Unroe Kathleen T. , Sachs Greg A. , Dennis M. E. , Hickman Susan E. , Stump Timothy E. , Tu Wanzhu , Callahan Christopher M.
Published: April 2016

Objectives

To analyze the costs for long‐stay (>90 days) nursing home (NH) decedents with and without hospice care.

Design

Retrospective cohort study using a 1999–2009 data set of linked Medicare and Medicaid claims and minimum data set (MDS) assessments.

Setting

IndianaNHs.

Participants

Long‐stayNHdecedents (N = 2,510).

Measurements

Medicare costs were calculated for 2, 7, 14, 30, 90, and 180 days before death; Medicaid costs were calculated for dual‐eligible beneficiaries. Total costs and costs for hospice,NH, and inpatient care are reported.

Results

Of 2,510 long‐stayNHdecedents, 35% received hospice. Mean length of hospice was 103 days (median 34 days). Hospice users were more likely to have cancer (P< .001), a do‐not‐resuscitate order in place (P< .001), greater cognitive impairment (P< .001), and worse activity of daily living (ADL) function (P< .001) and less likely to have had a hospitalization in the year before death (P< .001). In propensity score analyses, hospice users had lower total Medicare costs for all time periods up to and including 90 days before death. For dually eligible beneficiaries, overall costs and Medicare costs were significantly lower for hospice users up to 30 days before death. Medicaid costs were not different between the groups except for the 2‐day time period.

Conclusion

In this analysis of costs to Medicare and Medicaid for long‐stayNHdecedents, use of hospice did not increase costs in the last 6 months of life. Evidence supporting cost savings is sensitive to analyses that vary the time period before death.
Vitamin E supplementation inhibits muscle damage and inflammation after moderate exercise in hypoxia
Authors: Santos S. A. , Silva E. T. , Caris A. V. , Lira F. S. , Tufik S. , dos Santos R. V. T.
Published: April 2016

Background

Exercise under hypoxic conditions represents an additional stress in relation to exercise in normoxia. Hypoxia induces oxidative stress and inflammation as mediated through tumour necrosis factor (TNF)‐α release that might be exacerbated through exercise. In addition, vitamin E supplementation might attenuate oxidative stress and inflammation resulting from hypoxia during exercise. The present study aimed to evaluate the effects of vitamin E supplementation (250 mg) on inflammatory parameters and cellular damage after exercise under hypoxia simulating an altitude of 4200 m.

Methods

Nine volunteers performed three sessions of 60 min of exercise (70% maximal oxygen uptake) interspersed for 1 week under normoxia, hypoxia and hypoxia after vitamin E supplementation 1 h before exercise. Blood was collected before, immediately after and at 1 h after exercise to measure inflammatory parameters and cell damage.

Results

Percentage oxygen saturation of haemoglobin decreased after exercise and recovered 1 h later in the hypoxia + vitamin condition (P < 0.05). Supplementation decreased creatine kinase (CK)‐TOTAL, CK‐MB and lactate dehydrogenase 1 h after exercise (P < 0.05). The exercise in hypoxia increased interleukin (IL)‐6, TNF‐α, IL‐1ra and IL‐10 immediately after exercise (P < 0.05). Supplementation reversed the changes observed after exercise in hypoxia without supplementation (P < 0.05).

Conclusions

We conclude that 250 mg of vitamin E supplementation at 1 h before exercise reduces cell damage markers after exercise in hypoxia and changes the concentration of cytokines, suggesting a possible protective effect against inflammation induced by hypoxia during exercise.
Financial Distress Prediction in an International Context: A Review and Empirical Analysis of Altman's Z‐Score Model
Authors: Altman Edward I. , Iwanicz‐Drozdowska Małgorzata , Laitinen Erkki K. , Suvas Arto
Published: April 2016

This paper assesses the classification performance of the Z‐Score model in predicting bankruptcy and other types of firm distress, with the goal of examining the model's usefulness for all parties, especially banks that operate internationally and need to assess the failure risk of firms. We analyze the performance of the Z‐Score model for firms from 31 European and three non‐European countries using different modifications of the original model. This study is the first to offer such a comprehensive international analysis. Except for the United States and China, the firms in the sample are primarily private, and include non‐financial companies across all industrial sectors. We use the original Z′′‐Score model developed by Altman, Corporate Financial Distress: A Complete Guide to Predicting, Avoiding, and Dealing with Bankruptcy (1983) for private and public manufacturing and non‐manufacturing firms. While there is some evidence that Z‐Score models of bankruptcy prediction have been outperformed by competing market‐based or hazard models, in other studies, Z‐Score models perform very well. Without a comprehensive international comparison, however, the results of competing models are difficult to generalize. This study offers evidence that the general Z‐Score model works reasonably well for most countries (the prediction accuracy is approximately 0.75) and classification accuracy can be improved further (above 0.90) by using country‐specific estimation that incorporates additional variables.
Evolution of the microstructure of unmodified and polymer modified asphalt binders with aging in an accelerated weathering tester
Authors: MENAPACE ILARIA , MASAD EYAD
Published: April 2016

This paper presents findings on the evolution of the surface microstructure of two asphalt binders, one unmodified and one polymer modified, directly exposed to aging agents with increasing durations. The aging is performed using an accelerated weathering tester, where ultraviolet radiation, oxygen and an increased temperature are applied to the asphalt binder surface. Ultraviolet and dark cycles, which simulated the succession of day and night, alternated during the aging process, and also the temperature varied, which corresponded to typical summer day and night temperatures registered in the state of Qatar. Direct aging of an exposed binder surface is more effective in showing microstructural modifications than previously applied protocols, which involved the heat treatment of binders previously aged with standardized methods. With the new protocol, any molecular rearrangements in the binder surface after aging induced by the heat treatment is prevented. Optical photos show the rippling and degradation of the binder surface due to aging. Microstructure images obtained by means of atomic force microscopy show gradual alteration of the surface due to aging. The original relatively flat microstructure was substituted with a profoundly different microstructure, which significantly protrudes from the surface, and is characterized by various shapes, such as rods, round structures and finally ‘flower’ or ‘leaf’ structures.
Immunomodulation – a disease‐modifying avenue for treatment of Huntington's disease?
Authors: Björkqvist Maria
Published: April 2016

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This Editorial highlights a study published in the current issue of Journal of Neurochemistry by Dobson et al. (), investigating whether the immunomodulatory agent, laquinimod exerts an immunomodulatory effect on isolated Huntington's disease monocytes. In Huntington's disease (HD) a central immune activation is mirrored in the periphery by a low‐grade immune response and monocytes isolated from HD gene carriers have been shown pathologically hyperreactive in response to stimulation. This hyperreactive immune system has become recognized as an important feature of HD pathogenesis and the employment of a strategy to affect this hyperreactivity could be a potential disease‐modifying avenue in HD.

Read the highlighted article ‘Laquinimod dampens hyperactive cytokine production in Huntington's disease patient myeloid cells’ on page 782.
Richard Hudson Quarles (1939–2015)
Authors: Johnson David , Boullerne Anne , DeVries George
Published: April 2016

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This is an obituary for Richard Hudson Quarles, an internationally renowned neuroscientist, who retired in 2007 after 39 years at the National Institutes of Health, and who died August 9, 2015 in Sandy Spring, Maryland, USA. Richard Hudson Quarles, circa 1984, courtesy of The NIH Record newsletter.
Myosin light chain kinase facilitates endocytosis of synaptic vesicles at hippocampal boutons
Authors: Li Lin , Wu Xiaomei , Yue Hai‐Yuan , Zhu Yong‐Chuan , Xu Jianhua
Published: April 2016

At nerve terminals, endocytosis efficiently recycles vesicle membrane to maintain synaptic transmission under different levels of neuronal activity. Ca2+ and its downstream signal pathways are critical for the activity‐dependent regulation of endocytosis. An activity‐ and Ca2+‐dependent kinase, myosin light chain kinase (MLCK) has been reported to regulate vesicle mobilization, vesicle cycling, and motility in different synapses, but whether it has a general contribution to regulation of endocytosis at nerve terminals remains unknown. We investigated this issue at rat hippocampal boutons by imaging vesicle endocytosis as the real‐time retrieval of vesicular synaptophysin tagged with a pH‐sensitive green fluorescence protein. We found that endocytosis induced by 200 action potentials (5–40 Hz) was slowed by acute inhibition of MLCK and down‐regulation of MLCK with RNA interference, while the total amount of vesicle exocytosis and somatic Ca2+ channel current did not change with MLCK down‐regulation. Acute inhibition of myosin II similarly impaired endocytosis. Furthermore, down‐regulation of MLCK prevented depolarization‐induced phosphorylation of myosin light chain, an effect shared by blockers of Ca2+ channels and calmodulin. These results suggest that MLCK facilitates vesicle endocytosis through activity‐dependent phosphorylation of myosin downstream of Ca2+/calmodulin, probably as a widely existing mechanism among synapses. Our study suggests that MLCK is an important activity‐dependent regulator of vesicle recycling in hippocampal neurons, which are critical for learning and memory.

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The kinetics of vesicle membrane endocytosis at nerve terminals has long been known to depend on activity and Ca2+. This study provides evidence suggesting that myosin light chain kinase increases endocytosis efficiency at hippocampal neurons by mediating Ca2+/calmodulin‐dependent phosphorylation of myosin. The authors propose that this signal cascade may serve as a common pathway contributing to the activity‐dependent regulation of vesicle endocytosis at synapses.
Proteome rearrangements after auditory learning: high‐resolution profiling of synapse‐enriched protein fractions from mouse brain
Authors: Kähne Thilo , Richter Sandra , Kolodziej Angela , Smalla Karl‐Heinz , Pielot Rainer , Engler Alexander , Ohl Frank W. , Dieterich Daniela C. , Seidenbecher Constanze , Tischmeyer Wolfgang , Naumann Michael , Gundelfinger Eckart D.
Published: April 2016

Learning and memory processes are accompanied by rearrangements of synaptic protein networks. While various studies have demonstrated the regulation of individual synaptic proteins during these processes, much less is known about the complex regulation of synaptic proteomes. Recently, we reported that auditory discrimination learning in mice is associated with a relative down‐regulation of proteins involved in the structural organization of synapses in various brain regions. Aiming at the identification of biological processes and signaling pathways involved in auditory memory formation, here, a label‐free quantification approach was utilized to identify regulated synaptic junctional proteins and phosphoproteins in the auditory cortex, frontal cortex, hippocampus, and striatum of mice 24 h after the learning experiment. Twenty proteins, including postsynaptic scaffolds, actin‐remodeling proteins, and RNA‐binding proteins, were regulated in at least three brain regions pointing to common, cross‐regional mechanisms. Most of the detected synaptic proteome changes were, however, restricted to individual brain regions. For example, several members of the Septin family of cytoskeletal proteins were up‐regulated only in the hippocampus, while Septin‐9 was down‐regulated in the hippocampus, the frontal cortex, and the striatum. Meta analyses utilizing several databases were employed to identify underlying cellular functions and biological pathways. Data are available via ProteomeExchange with identifier PXD003089.

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How does the protein composition of synapses change in different brain areas upon auditory learning? We unravel discrete proteome changes in mouse auditory cortex, frontal cortex, hippocampus, and striatum functionally implicated in the learning process. We identify not only common but also area‐specific biological pathways and cellular processes modulated 24 h after training, indicating individual contributions of the regions to memory processing.
Limited predictability of postmortem human brain tissue quality by RNA integrity numbers
Authors: Sonntag Kai‐C. , Tejada George , Subburaju Sivan , Berretta Sabina , Benes Francine M. , Woo Tsung‐Ung W.
Published: April 2016

The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the availability of intact mRNA. Using the Agilent bioanalyzer and qRT‐PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3′–5′ mRNA sequences of the cytochrome C‐1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT‐PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full‐length transcripts, despite the variable degree of linear degradation along the 3′–5′ sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality.

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Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs.
Visualization of Data Regarding Infections Using Eye Tracking Techniques
Authors: Yoon Sunmoo , Cohen Bevin , Cato Kenrick D. , Liu Jianfang , Larson Elaine L.
Published: April 2016

Objective

To evaluate ease of use and usefulness for nurses of visualizations of infectious disease transmission in a hospital.

Design

An observational study was used to evaluate perceptions of several visualizations of data extracted from electronic health records designed using a participatory approach. Twelve nurses in the master's program in an urban research‐intensive nursing school participated in May 2015.

Methods

A convergent parallel mixed method was used to evaluate nurses’ perceptions on ease of use and usefulness of five visualization conveying trends in hospital infection transmission applying think‐aloud, interview, and eye‐tracking techniques.

Findings

Subjective data from the interview and think‐aloud techniques indicated that participants preferred the traditional line graphs in simple data representation due to their familiarity, clarity, and easiness to read. An objective quantitative measure of eye movement analysis (444,421 gaze events) identified a high degree of participants’ attention span in infographics in all three scenarios. All participants responded with the correct answer within 1 min in comprehensive tests.

Conclusions

A user‐centric approach was effective in developing and evaluating visualizations for hospital infection transmission. For the visualizations designed by the users, the participants were easily able to comprehend the infection visualizations on both line graphs and infographics for simple visualization. The findings from the objective comprehension test and eye movement and subjective attitudes support the feasibility of integrating user‐centric visualization designs into electronic health records, which may inspire clinicians to be mindful of hospital infection transmission. Future studies are needed to investigate visualizations and motivation, and the effectiveness of visualization on infection rate.

Clinical Relevance

This study designed visualization images using clinical data from electronic health records applying a user‐centric approach. The design insights can be applied for visualizing patient data in electronic health records.
Simulation in Nursing Education—International Perspectives and Contemporary Scope of Practice
Authors: Kelly Michelle A. , Berragan Elizabeth , Husebø Sissel Eikeland , Orr Fiona
Published: April 2016

Purpose

This article provides insights and perspectives from four experienced educators about their approaches to developing, delivering, and evaluating impactful simulation learning experiences for undergraduate nurses. A case study format has been used to illustrate the commonalities and differences of where simulation has been positioned within curricula, with examples of specialized clinical domains and others with a more generic focus. The importance of pedagogy in developing and delivering simulations is highlighted in each case study. A range of learning theories appropriate for healthcare simulations are a reminder of the commonalities across theories and that no one theory can account for the engaging and impactful learning that simulation elicits.

Clinical Relevance

Creating meaningful and robust learning experiences through simulation can benefit students’ performance in subsequent clinical practice. The ability to rehearse particular clinical scenarios, which may be difficult to otherwise achieve, assists students in anticipating likely patient trajectories and understanding how to respond to patients, relatives, and others in the healthcare team.