bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal activity‐dependent STAT3 localization to nucleus is dependent on Tyr‐705 and Ser‐727 phosphorylation in rat hippocampal neurons
Authors: Murase Sachiko , McKay Ronald D.
Published: November 2013

Signal transducer and activator of transcription 3 (STAT3) dramatically increases during the first post‐natal week, and supports the survival of mature hippocampal neurons. Recently, we reported that chronic elevation of excitability leads to a loss of STAT3 signal, inducing vulnerability in neurons. The loss of STAT3 signal was due to impaired Erk1/2 activation. While overnight elevation of activity attenuated STAT3 signal, brief low‐frequency stimuli, which induce long‐term depression, have been shown to activate STAT3. Here we investigated how STAT3 responds to depolarization in mature neurons. A brief depolarization results in the transient activation of STAT3: it induces calcium influx through L‐type voltage‐gated calcium channels, which triggers activation of Src family kinases. Src family kinases are required for phosphorylation of STAT3 at Tyr‐705 and Ser‐727. PTyr‐705 is Janus kinase (JAK)‐dependent, while PSer‐727 is dependent on Akt, the Ser/Thr kinase. Both PTyr‐705 and PSer‐727 are necessary for nuclear translocation of STAT3 in these neurons. Chronic elevation of spontaneous activity by an A‐type potassium blocker, 4‐aminopyridine (4‐AP), also induced the transient phosphorylation of STAT3, which after 4 h fell to basal levels despite the presence of 4‐AP. These results suggest that phasic and chronic neuronal activation induce distinct molecular pathways, resulting in opposing regulation of STAT3 signal.
Lost potential of kidney and liver donors amongst deceased intracerebral hemorrhage patients
Authors: Sairanen T. , Koivisto A. , Koivusalo A.‐M. , Rantanen K. , Mustanoja S. , Meretoja A. , Putaala J. , Strbian D. , Kaste M. , Isoniemi H. , Tatlisumak T.
Published: November 2013

Background and purpose

Intracerebral hemorrhage (ICH) has high acute mortality. The number of potential kidney and liver donors amongst deceased ICH patients was estimated to improve our institutional guidelines on acute care of neurocritical patients to increase organ donation.

Methods

A chart review was carried out by a multi‐professional team for consecutive ICH patients admitted to the emergency department at Helsinki University Central Hospital and dying within 14 days between 2005 and 2010.

Results

In all, 955 patients had follow‐up data, of whom 254 (27%) died within 14 days and eight ended up as organ donors. An additional 51 potentially suitable donors not different from actual donors were identified: nine suitable for kidney donation, 11 for liver and 31 for both. In 49/51 (96%) cases prognosis seemed non‐existent and do‐not‐resuscitate orders were issued early, which led to refrainment from intensive care in 76.5%. These potential donors differed from those ICH patients surviving a whole year (n = 529) by male preponderance, more severe symptoms (median National Institutes of Health Stroke Scale 25 vs. 6 and Glasgow Coma Scale 7 vs. 15), larger hematoma volumes of 24.8 cm3 (vs. 6.7), and frequent finding of midline shift and intraventricular rupture of the hemorrhage in admission brain CT. Based on the results, our guidelines were revised towards more active treatment including mechanical ventilation for neurocritical patients at the emergency department for at least 48 h, resulting in an increase in organ donations in 2012.

Conclusions

A considerable number of ICH patients are potential organ donors if the evaluation takes place on arrival and organ donation is considered as part of usual end‐of‐life care.
Simple clinical predictors of stroke outcome based on National Institutes of Health Stroke Scale score during 1‐h recombinant tissue‐type plasminogen activator infusion
Authors: Osaki M. , Miyashita F. , Koga M. , Fukuda M. , Shigehatake Y. , Nagatsuka K. , Minematsu K. , Toyoda K.
Published: November 2013

Background and purpose

An index for predictors of stroke outcome was determined based on the National Institutes of Health Stroke Scale (NIHSS) scores during 1‐h intravenous administration of recombinant tissue‐type plasminogen activator (rt‐PA).

Methods

Stroke patients with baseline NIHSS score ≥8 and occlusion at the internal carotid or middle cerebral arteries (ICA, MCA) were retrospectively studied from a prospective single‐center registry. NIHSS scores and inverse change from baseline scores (ΔNIHSS) were assessed at 30 min and 1 h after rt‐PA infusion. Patients were divided into two groups according to arterial occlusion sites: group P, ICA or proximal M1; and group D, distal M1 or M2. A modified Rankin Scale score of 2–6 at 3 months was defined as an unfavorable outcome.

Results

In all 108 patients, the cutoff NIHSS score predicting unfavorable outcome was ≥12 and cutoff ΔNIHSS scores were ≤2 at both 30 min and 1 h. In group P (n = 36), the cutoff NIHSS score was ≥14 at both 30 min and 1 h and cutoff ΔNIHSS scores were ≤1 at 30 min and ≤2 at 1 h. Unfavorable outcome was seen in all patients with NIHSS1 h ≥ 14, ΔNIHSS30 min ≤ 1 and ΔNIHSS1 h ≤ 2. In group D (n = 72), the cutoff NIHSS scores were ≥12 at both 30 min and 1 h, and cutoff ΔNIHSS scores were ≤2 at 30 min and ≤7 at 1 h; 90% of patients with unfavorable outcome showed ΔNIHSS1 h ≤ 7.

Conclusion

NIHSS and ΔNIHSS during 1‐h rt‐PA infusion seemed predictive of 3‐month outcome when the site of arterial occlusion was identified prior to rt‐PA.
Periplasmic glucose‐binding protein from Pseudomonas putida CSV86 – identification of the glucose‐binding pocket by homology‐model‐guided site‐specific mutagenesis
Authors: Modak Arnab , Bhaumik Prasenjit , Phale Prashant S.
Published: November 2013

Glucose transport in Pseudomonas putida CSV86 is mediated via a periplasmic glucose‐binding protein (GBP)‐dependent putative glucose ABC transporter. Here we describe a homology model and functional characterization of GBP from CSV86 (ppGBP). A whole‐cell [14C]‐glucose uptake study revealed that glucose is transported by the high‐affinity intracellular phosphorylative pathway. ppGBP was cloned, over‐expressed in Escherichia coli and purified to apparent homogeneity. The purified ppGBPs from both E. coli and CSV86 were found to be specific for glucose. A homology model of ppGBP was constructed that resembles the class II family of periplasmic binding proteins. The model showed highest structural similarity to GBP of Thermus thermophilus (ttGBP, rmsd 0.64 Å). Structural analysis and molecular docking studies predicted W35, W36, E41, K92, K339 and H379 of ppGBP as putative glucose‐binding residues. Alanine substitution of these residues resulted in significantly reduced [14C]‐glucose binding activity. Analysis of the operonic arrangement and structural comparative studies suggested that ppGBP and ttGBP probably originated from a common ancestor. Structural adaptations that inhibit binding of di‐ or trisaccharides at the glucose‐binding pocket of ppGBP were also identified.
Understanding posttraumatic stress disorder: insights from the methylome
Authors: Malan‐Müller S. , Seedat S. , Hemmings S. M. J.
Published: November 2013

Genome‐wide association studies (GWAS) have identified numerous disease‐associated variants; however, these variants have a minor effect on disease and explain only a small amount of the heritability of complex disorders. The search for the missing heritability has shifted attention to rare variants, copy number variants, copy neutral variants and epigenetic modifications. The central role of epigenetics, and specifically DNA methylation, in disease susceptibility and progression has become more apparent in recent years. Epigenetic mechanisms facilitate the response to environmental changes and challenges by regulating gene expression. This makes the study of DNA methylation in psychiatric disorders such as posttraumatic stress disorder (PTSD) highly salient, as the environment plays such a vital role in disease aetiology. The epigenome is dynamic and can be modulated by numerous factors, including learning and memory, which are important in the context of PTSD. Numerous studies have shown the effects of early life events, such as maternal separation and traumas during adulthood, on DNA methylation patterns and subsequent gene expression profiles. Aberrations in adaptive DNA methylation contribute to disease susceptibility when an organism is unable to effectively respond to environmental demands. Epigenetic mechanisms are also involved in higher order brain functions. Dysregulation of methylation is associated with neurodevelopmental and neurodegenerative cognitive disorders, affective disorders, addictive behaviours and altered stress responses. A thorough understanding of how the environment, methylome and transcriptome interact and influence each other in the context of fear and anxiety is integral to our understanding and treatment of stress‐related disorders such as PTSD.
From projected species distribution to food‐web structure under climate change
Authors: Albouy Camille , Velez Laure , Coll Marta , Colloca Francesco , Le Loc'h François , Mouillot David , Gravel Dominique
Published: November 2013

Climate change is inducing deep modifications in species geographic ranges worldwide. However, the consequences of such changes on community structure are still poorly understood, particularly the impacts on food‐web properties. Here, we propose a new framework, coupling species distribution and trophic models, to predict climate change impacts on food‐web structure across the Mediterranean Sea. Sea surface temperature was used to determine the fish climate niches and their future distributions. Body size was used to infer trophic interactions between fish species. Our projections reveal that 54 fish species of 256 endemic and native species included in our analysis would disappear by 2080–2099 from the Mediterranean continental shelf. The number of feeding links between fish species would decrease on 73.4% of the continental shelf. However, the connectance of the overall fish web would increase on average, from 0.26 to 0.29, mainly due to a differential loss rate of feeding links and species richness. This result masks a systematic decrease in predator generality, estimated here as the number of prey species, from 30.0 to 25.4. Therefore, our study highlights large‐scale impacts of climate change on marine food‐web structure with potential deep consequences on ecosystem functioning. However, these impacts will likely be highly heterogeneous in space, challenging our current understanding of climate change impact on local marine ecosystems.
Increased cardiovascular risk in patients with severe mental illness
Authors: Gladigau E. L. , Fazio T. N. , Hannam J. P. , Dawson L. M. , Jones S. G.
Published: November 2013

Background

People with severe mental illness (SMI) have a reduced life expectancy. A major cause of mortality is cardiovascular disease.

Aims

The aims of this study were to document the prevalence of cardiovascular risk factors in people with SMI engaged in community psychiatric rehabilitation and compare prevalence rates to the general, and Aboriginal and Torres Strait Islander (ATSI) populations of Australia.

Method

A cross‐sectional audit was conducted on patients receiving care from Melbourne's Inner‐West Area Mental Health Service. Profiles were collected on: smoking status, body mass index, waist circumference, blood pressure, diabetic status and fasting lipid profiles. These were compared with the general and ATSI Australian populations.

Results

Complete data were available for 60 patients. Most were involuntary patients with a diagnosis of schizophrenia or schizoaffective disorder. Patients were more likely to smoke, be obese, have dyslipidaemia and the metabolic syndrome compared with the general and ATSI populations of Australia. Patients were more likely to have diabetes than the general population but had similar rates to the ATSI population. Patients had similar rates of hypertension to the general population but were less likely to be hypertensive compared with the ATSI population.

Conclusion

Australians living with SMI have very high rates of cardiovascular risk factors, far in excess of the general Australian population and comparable with the ATSI population.
Functional polymorphisms of TLR8 are associated with hepatitis C virus infection
Authors: Wang Chiou‐Huey , Eng Hock‐Liew , Lin Kuei‐Hsiang , Liu Hsiang‐Chun , Chang Cheng‐Hsien , Lin Tsun‐Mei
Published: November 2013

Chronic hepatitis C virus (HCV) infection is a worldwide threat to public health. Toll‐like receptor 8 (TLR8) is critical for eliminating RNA viruses, and variation within the TLR8 gene may alter the function of TLR8 in response to HCV infection. Our previous study demonstrated that the TLR8‐129G>C (rs3764879) and TLR8+1G>A (rs3764880) variants were in complete linkage disequilibrium, and that the frequency of TLR8‐129C/+1A was significantly higher in male patients with HCV infection compared with the healthy controls. In the present study, we found that the promoter activity of TLR8‐129G was higher than that of TLR8‐129C in THP‐1 cells. Moreover, TLR8‐129G mRNA stability and competitive DNA‐binding ability were significantly lower than that of TLR8‐129C. To investigate the functional effects of TLR8 polymorphisms, we compared the nuclear factor‐κB (NF‐κB)‐driven luciferase activity in HEK293 cells transfected with the TLR8 variants. TLR8+1A plasmids induced less NF‐κB signalling than did those transfected with TLR8+1G after 20 μm CL075 (P = 0·011) stimulation. We also analysed the mRNA expression and cytokine production in whole blood and monocytes from people of various genotypes stimulated ex vivo by the interferon‐γ and TLR7/8 agonist CL075, R848. TLR8 expression in CD14+ cells derived from volunteers with TLR8‐129G/+1G was significantly higher than that derived from TLR8‐129C/+1A, and interleukin‐12p40 production was higher in volunteers with TLR8‐129G/+1G after stimulation. The data indicate that variations in TLR8 genes may modulate immune responses during HCV infection.
Clinical diagnosis of pandemic A(H1N1) 2009 influenza in children with negative rapid influenza diagnostic test by lymphopenia and lower C‐reactive protein levels
Authors: Wang Lin , Chang Ling‐Sai , Lee Ing‐Kit , Tang Kuo‐Shu , Li Chung‐Chen , Eng Hock‐Liew , You Huey‐Ling , Yang Kuender D.
Published: November 2013

Background

The sensitivity of rapid influenza diagnostic test (RIDT) of children with influenza‐like illness (ILI) remains low.

Objective

We compare the parameters between pandemic A(H1N1) 2009 influenza with negative RIDT and ILI not H1N1 for improving the low sensitivity of RIDT for children with ILI.

Methods

In a cohort of consecutive laboratory‐confirmed H1N1 influenza, we identified 150 H1N1 children with positive RIDT, 152 H1N1 children with negative RIDT, and 75 children with ILI not H1N1. Viral load in throat, complete blood count (CBC), and C‐reactive protein (CRP) levels between H1N1 children with negative RIDT and children with ILI not H1N1 were assessed.

Results

The diagnostic sensitivity of the RIDT was 45·5%. An analysis of CBC and CRP levels indicated that H1N1 children with negative RIDT had lower total leukocyte, neutrophil, lymphocyte, and basophil counts, and serum CRP levels (P < 0·01). Lymphocyte counts less than 1500 cells/mm3 and CRP levels <15 mg/l, determined by a receiver operating characteristic curve, showed a diagnostic sensitivity of 52·5% and 80·7%, respectively. Combining the lymphocyte counts and CRP levels provided a diagnostic sensitivity of 91·5%. Moreover, H1N1 children with negative RIDT had a lower viral load than those with positive RIDT (3·33 versus 4·48 log10 copies/ml, P < 0·001); the viral load was negatively correlated to the lymphocyte count (P < 0·001).

Conclusions

A combination of a low lymphocyte count and a low CRP level could, in the early disease phase, provide a useful screening for H1N1 children with false‐negative RIDT, potentially facilitating differential diagnoses.
Influenza outbreak control practices and the effectiveness of interventions in long‐term care facilities: a systematic review
Authors: Rainwater‐Lovett Kaitlin , Chun Kevin , Lessler Justin
Published: November 2013

Background

Evaluation of influenza control measures frequently focuses on the efficacy of chemoprophylaxis and vaccination, while the effectiveness of non‐pharmaceutical interventions (NPI) receives less emphasis. While influenza control measures are frequently reported for individual outbreaks, there have been few efforts to characterize the real‐world effectiveness of these interventions across outbreaks.

Objectives

To characterize influenza case and outbreak definitions and control measures reported by long‐term care facilities (LTCFs) of elderly adults and estimate the reduction in influenza‐like illness (ILI) attack rates due to chemoprophylaxis and NPI.

Methods

We conducted a literature search in PubMed including English‐language studies reporting influenza outbreaks among elderly individuals in LTCFs. A Bayesian hierarchical logistic regression model estimated the effects of control measures on ILI attack rates.

Results

Of 654 articles identified in the literature review, 37 articles describing 60 influenza outbreaks met the inclusion criteria. Individuals in facilities where chemoprophylaxis was used were significantly less likely to develop influenza A or B than those in facilities with no interventions [odds ratio (OR) 0·48, 95% CI: 0·28, 0·84]. Considered by drug class, adamantanes significantly reduced infection risk (OR 0·22, 95% CI: 0·12, 0·42), while neuraminidase inhibitors did not show a significant effect. Although NPI showed no significant effect, the results suggest that personal protective equipment may produce modest protective effects.

Conclusions

Our results indicate pharmaceutical control measures have the clearest reported protective effect in LTCFs. Non‐pharmaceutical approaches may be useful; however, most data were from observational studies and standardized reporting or well‐conducted clinical trials of NPI are needed to more precisely measure these effects.
Appropriate physical activity and dietary intake achieve optimal metabolic control in older type 2 diabetes patients
Authors: Huang Jui‐Hua , Cheng Fu‐Chou , Tsai Leih‐Ching , Lee Ning‐Yuean , Lu Yi‐Fa
Published: November 2013

Aims/Introduction

The aim of the present study was to investigate an appropriate level of physical activity and optimal dietary intake in older type 2 diabetes patients.

Materials and Methods

The cross‐sectional study enrolled 210 older type 2 diabetes patients. Participants were interviewed to obtain information on physical activity, 24‐h dietary recall and typical weekly dietary patterns. Anthropometric measurements, and biochemical analysis of blood and urine were determined.

Results

Moderate physical activity (either moderate leisure‐time physical activity or moderate physical activity level) and diet with protein intake of ≥0.8 g/kg/day were associated with lower glycated hemoglobin and triglyceride, higher high‐density lipoprotein, lower waist circumference, body mass index and body fat, as well as better serum magnesium and albumin levels in older diabetic patients. In contrast, inadequate protein intake was correlated with higher glycated hemoglobin, triglyceride, body fat percentage, waist circumference and body mass index. In addition, high physical activity with inadequate protein and magnesium intake might exacerbate magnesium deficiency, resulting in poor glycemic control in older diabetic patients. Furthermore, low physical activity and inadequate protein intake were linked with poor glycemic control, and lower high‐density lipoprotein, and higher triglyceride, body fat percentage, waist circumference and body mass index.

Conclusions

Moderate physical activity and adequate dietary protein intake (≥0.8 g/kg/day) might be the optimal recommendation for better metabolic control in older adults with type 2 diabetes.
The Imbalance of Th17 cells and CD4+CD25highFoxp3+ Treg cells in patients with atopic dermatitis
Authors: Ma L. , Xue H.‐B. , Guan X.‐H. , Shu C.‐M. , Wang F. , Zhang J.‐H. , An R.‐Z.
Published: November 2013

Background

Th17/Treg imbalance is involved in several autoimmune, inflammatory and allergic reactions. Nevertheless, the possible contribution of Th17/Treg imbalance in atopic dermatitis (AD) remains unknown.

Objective

To explore the possible role of Th17/Treg imbalance in AD.

Methods

Th17 and Treg cells percentage in peripheral blood mononuclear cells (PBMCs) and skin specimens, specific transcription factor retinoic acid‐related orphan receptor (ROR)γt and Foxp3 mRNA levels in PBMCs, as well as Th17‐ and Treg‐related cytokines mRNA levels in PBMCs, serum concentrations, and expression levels in PBMCs culture supernatant after recombinant Dermatophagoides pteronyssinus antigen stimulation were detected in AD patients. Controls included patients with psoriasis, allergic contact dermatitis (ACD) and healthy donors.

Results

Th17 cells percentage, RORγt, IL‐17 and IL‐23 levels in peripheral circulation of AD patients were significantly higher than those in ACD patients and healthy controls, but lower than those of psoriasis patients. Treg cells percentage, Foxp3 and TGF‐β mRNA levels were reduced in AD patients compared with healthy controls, while there were no significant differences among AD, ACD and psoriasis patients. Th17 cells percentage, IL‐17 and IL‐23 levels were increased, while Treg cells percentage and TGF‐β level were decreased in AD lesion and PBMCs culture supernatant respectively. There was a negative association between Th17 and Treg cells percentage in AD patients. AD severity score positively correlated with Th17 cells percentage and Th17/Treg ratio, while negatively correlated with Treg cells percentage. Serum IgE levels positively correlated with Th17/Treg ratio.

Conclusion

In AD, there exists an immune imbalance in Th17 and Treg cells, which may contribute to its pathogenesis and development.
Quality of reporting clinical trials published in five leading Sri Lankan medical journals
Authors: Abeysena Chrishantha , Poddalgoda Indeewari
Published: November 2013

Objectives

To assess the quality of reporting of clinical trials published in five leading Sri Lankan medical journals.

Methods

Six medical journals were hand searched for clinical trials published from 1982 to 2011. Eligible criteria were all randomized and non‐randomized clinical trials conducted in humans. A checklist was developed based on CONSORT and TREND recommendations. Each study was independently evaluated by two reviewers. Outcome measures were presence of checklist items in published reports.

Results

Fifteen randomized and 24 non‐randomized parallel group trials from 724 studies in five journals met the inclusion criteria. Out of 39 trials, 39 (97%) clearly described the objectives, 16 (41%) defined the periods of recruitment, 7 (18%) reported how sample size was determined, 10 (25.6%) reported the methods to enhance the quality of measurements, 20 (51%) reported baseline demographic and clinical characteristics of each group, 4 (10%) showed flow diagrams, 23 (69%) reported statistical methods used to compare groups for primary outcomes, 21 (54%) reported effect size, 4 (10%) reported its precision, and 20 (51%) interpreted the results in the context of current evidence, and 5 (13%) described the generalizability of the findings. Of the 15 randomized trials, only one (7%) reported sequence generation, 5 (33%) allocation concealment, 9 (60%) reported blinding status of participants or investigators, and 2 (13%) reported intention to treat analysis.

Conclusions

Reporting of several essential recommendations remained suboptimal. Education and training of trial methods and awareness of the CONSORT and TREND statements and more attention to the quality of reporting may improve matters.
Evidence‐based healthcare and the Cochrane Collaboration: An unfinished journey as yet!
Authors: Meyer Sascha
Published: November 2013

Objective

Although evidence‐based medicine and the Cochrane Collaboration have become key players in modern medicine, it is important to note that evidencebased medicine and the Cochrane Collaboration are confronted with a number of substantial challenges that need to be addressed. The aim of this work is to highlight some of these problems.

Methods

This comment is based on a semi‐structured literature review and my personal experience in the field of evidence‐based medicine.

Results

In this comment, 3 important areas of controversy and conflict (“Improving the quality of Cochrane Review”; “Increasing the relevance to middle‐ and low‐income countries”; and “Keeping reviews up to date”) will be highlighted, and possible solutions will be presented.

Conclusion

With the Cochrane Collaboration now having been at the forefront of promoting and implementing core principles of evidence‐based medicine, further organizational, political and administrative efforts will have to be put in place to further improve the impact of evidence‐based medicine in the field of health care. This process can best be realized through networking and cooperation of the medical community worldwide, irrespective of geographic origin. When successfully tackling the above mentioned issues and obstacles, the already amazing success story of evidence‐based medicine and the Cochrane Collaboration will grow even more substantial.
Finding and filling the gaps in the evidence with high quality clinical trials – the experience of one Cochrane Review Group
Authors: Jahnke Nikki , Remmington Tracey , Smyth Alan R
Published: November 2013

The Cochrane Cystic Fibrosis and Genetic Disorders Group publishes systematic reviews of randomized trials for many genetic disorders. Given the rarity of these disorders, there are often few relevant trials to be included. Therefore, it is common for the reviews to be ‘empty’ and unable to present evidence which aids decision‐making in clinical practice. However, we do not regard this as negative; rather we see this as a challenge and an opportunity to influence the research agenda. We have several reviews which clearly illustrate the cycle of assessing the evidence base, identifying the lack of data, generating high quality research and incorporating the resulting data into the original systematic review.
Diversity of the Luciferin Binding Protein Gene in Bioluminescent Dinoflagellates – Insights from a New Gene in Noctiluca scintillans and Sequences from Gonyaulacoid Genera
Authors: Valiadi Martha , Iglesias‐Rodriguez Maria Debora
Published: November 2013

Dinoflagellate bioluminescence systems operate with or without a luciferin binding protein, representing two distinct modes of light production. However, the distribution, diversity, and evolution of the luciferin binding protein gene within bioluminescent dinoflagellates are not well known. We used PCR to detect and partially sequence this gene from the heterotrophic dinoflagellate Noctiluca scintillans and a group of ecologically important gonyaulacoid species. We report an additional luciferin binding protein gene in N. scintillans which is not attached to luciferase, further to its typical combined bioluminescence gene. This supports the hypothesis that a profound re‐organization of the bioluminescence system has taken place in this organism. We also show that the luciferin binding protein gene is present in the genera Ceratocorys, Gonyaulax, and Protoceratium, and is prevalent in bioluminescent species of Alexandrium. Therefore, this gene is an integral component of the standard molecular bioluminescence machinery in dinoflagellates. Nucleotide sequences showed high within‐strain variation among gene copies, revealing a highly diverse gene family comprising multiple gene types in some organisms. Phylogenetic analyses showed that, in some species, the evolution of the luciferin binding protein gene was different from the organism's general phylogenies, highlighting the complex evolutionary history of dinoflagellate bioluminescence systems.
Treatment of patients with dual hepatitis C virus and hepatitis B virus infection: Resolved and unresolved issues
Authors: Liu Chun‐Jen
Published: November 2013

Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is not uncommon in HCV or HBV endemic areas and among subjects at risk of parenteral transmission. In patients dually infected with hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In the past decade, the following issues have been resolved. In dually infected patients with active hepatitis C, combined pegylated interferon alfa plus ribavirin was effective, the treatment outcomes being similar to patients with HCV monoinfection. During long‐term follow‐up, the HCV response was sustained in around 97% of patients; and the long‐term outcomes including the development of hepatocellular carcinoma and liver‐related mortality were improved. However, several clinical issues remain to be resolved. First, host and viral factors influencing the long‐term outcomes and treatment options in patients with dual HCV/HBV infection await further studies. Second, about 60% of dually infected patients with baseline undetectable serum HBV DNA levels develop HBV reactivation after the start of treatment. How to prevent and treat HBV reactivation should be clarified. Third, about 30% of dually infected patients lose hepatitis B surface antigen at 5 years after the end of combination therapy; the mechanisms need further investigations. Fourth, the optimal treatment strategies for dually infected patients with active hepatitis B or established cirrhosis should be explored in future clinical trials. Finally, the role of new direct‐acting antiviral‐based therapy for the treatment of patients with dual HCV/HBV infection also remains to be evaluated.
Improvement of plant abiotic stress tolerance through modulation of the polyamine pathway
Authors: Shi Haitao , Chan Zhulong
Published: November 2013

Polyamines (mainly putrescine (Put), spermidine (Spd), and spermine (Spm)) have been widely found in a range of physiological processes and in almost all diverse environmental stresses. In various plant species, abiotic stresses modulated the accumulation of polyamines and related gene expression. Studies using loss‐of‐function mutants and transgenic overexpression plants modulating polyamine metabolic pathways confirmed protective roles of polyamines during plant abiotic stress responses, and indicated the possibility to improve plant tolerance through genetic manipulation of the polyamine pathway. Additionally, putative mechanisms of polyamines involved in plant abiotic stress tolerance were thoroughly discussed and crosstalks among polyamine, abscisic acid, and nitric oxide in plant responses to abiotic stress were emphasized. Special attention was paid to the interaction between polyamine and reactive oxygen species, ion channels, amino acid and carbon metabolism, and other adaptive responses. Further studies are needed to elucidate the polyamine signaling pathway, especially polyamine‐regulated downstream targets and the connections between polyamines and other stress responsive molecules.
Course of Depressive Symptoms across Pregnancy in African American Women
Authors: Wilusz Matthew J. , Peters Rosalind M. , Cassidy‐Bushrow Andrea E.
Published: November 2013

Introduction

Although African American women are at increased risk for antenatal depression, less is known regarding the course of antenatal depression symptoms among African American women. Because pregnancy is a state of rapid physical and mental changes, we examined if depression symptoms changed between the second and third trimesters in a sample of pregnant African American women.

Methods

A nonprobability sample of women was recruited from obstetrics clinics within a large Midwestern health system. African American women in their second trimester (N = 189) completed an initial study visit; a convenience sample of 37 women (19.6%) completed a second identical study visit during their third trimester. The 20‐item Center for Epidemiological Studies Depression Scale (CES‐D) was used to measure depressive symptoms; a CES‐D score of 16 or higher equates with clinical depression and a CES‐D score of 23 or higher indicates major depression. Paired t tests and correlation coefficients were used to estimate change in depression symptoms.

Results

Mean (SD) second‐ and third‐trimester CES‐D scores were not statistically significantly different (15.3 [10.6] and 15.1 [10.3], respectively; P = .87) and were moderately and significantly correlated (r = 0.65; P <.001). Prevalence of CES‐D scores of 16 or higher was 43.2% (n = 16) in the second trimester and 37.8% (n = 14) in the third trimester, which was not significantly different (P = .77). Between the 2 visits, 67.6% (n = 25) were classified identically with a CES‐D scores of 16 or higher with only fair agreement between the 2 measures (kappa = 0.33). Prevalence of CES‐D scores of 23 or higher was 27.0% (n = 10) and 21.6% (n = 8) in the second and third trimesters, respectively, and was not significantly different (P = .69). Between the 2 visits, 83.8% (n = 31) were classified identically with CES‐D scores of 23 or higher, with moderate agreement between the 2 measures (kappa = 0.56).

Discussion

Depression symptoms were relatively constant across the latter 2 trimesters of pregnancy. The second trimester may be an appropriate time to screen women for antenatal depression, as it is less likely to be affected by early‐pregnancy somatic events yet is early enough that intervention may impart positive health benefits for mother and child.
Powdery Mildew on Mulberry in Yunnan, China is Distinct from Other Phyllactinia spp. on Morus
Authors: Wang Jing‐Jie , Yang Li , Qiu Xin , Fan Rui , Ao Xiang , Zhou Wei , Li Jing‐Hua , Zhao Dong‐Yang , Wan Yong‐Ji
Published: November 2013

The occurrence of an epidemic outbreak of a powdery mildew disease on mulberry in Yunnan province, China, is reported. Its symptoms are characteristic for powdery mildews and visible as white pathches covering the abaxial surfaces of leaves leading to chlorosis and necrosis. The pathogen is morphologically barely distinguishable from Phyllactinia moricola. However, it exhibits several new morphological characteristics which 2–3 conidia could be formed in short chains at the apex of the conidiophores and the conidia could produce two germ tubes in any position. Phylogenetic analyses of ITS sequences show that the pathogen has a close genetic relationship with P. moricola and Ph. broussonetiae‐kaempferi, two species on hosts belonging to family Moraceae. However, the ITS differences between Japanese sequences and the Chinese sequence derived from mulberry are greater than expected for a single species and suggest a cryptic species in China, but the present data are not sufficient for a final conclusion. Therefore, the Morus powdery mildew in Yunnan can currently only be classified as Phyllactinia sp. Morphological features, including conidial germination pattern of this powdery mildew are described in detail, and the local climatic conditions of the disease are analysed, which will provide the base for finding an effective method, including bio‐control, to control the disease under local conditions.
Liquiritigenin exhibits antitumour action in pituitary adenoma cells via Ras/ERKs and ROS-dependent mitochondrial signalling pathways
Authors: Wang Di , Wong Hei-Kiu , Feng Yi-Bin , Zhang Zhang-Jin
Published: November 2013

Objective

The purpose of this study was to investigate antitumour effects of liquiritigenin (LQ) on pituitary adenoma in in-vitro and in-vivo models.

Methods

The effects of LQ on cell viability, apoptosis rate, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) level and various apoptosis-related mediators were examined in MMQ and GH3 cells that are derived from rat pituitary adenoma. Antitumour effect of LQ was also examined in the mouse model of GH3-xenografted tumour.

Key findings

LQ inhibited cell viability, caused G1 phase arrest and initiated apoptosis in both MMQ and GH3 cells. LQ dissipated MMP, increased intracellular ROS level and cytosol cytochrome C, and reduced the expression of Ras, B-cell lymphoma 2 and B-cell lymphoma-extra large. LQ also inhibited the activation of extracellular signalling-regulated kinases (ERKs) and the translocation of from cytoplasm to nucleus. LQ markedly reduced tumour size without affecting bodyweight in mice with GH3 cells xenograft.

Conclusions

LQ effectively inhibits pituitary adenoma tumour growth and induces cell apoptotic death mainly via Ras/ERKs and ROS-dependent mitochondrial pathways, suggesting that LQ is a potential suppressor of pituitary adenoma.
Clinical practice guidelines—Nursing management for pediatric patients with small bowel or multivisceral transplant
Authors: Bodeur Cynthia , Aucoin Julia , Johnson Raeanne , Garrison Kaitlyn , Summers Amanda , Schutz Kristen , Davis Megan , Woody Sherri , Ellington Kelly
Published: November 2013

Purpose

Small bowel or multivisceral transplant is a relatively new treatment for irreversible intestinal damage, and no published practice guidelines exist. The purpose of this article is to report evidence regarding the best plan of care to achieve adequate nutrition and appropriate development for children.

Design and Methods

An integrative review was conducted with 54 articles related to management of this transplant population. A nine‐member nursing team integrated the findings.

Practice Implications

This resulting guideline represents the best research and best practices on which to base staff education and competency validations to manage this medically fragile patient population.
Hepatitis C virus dysregulates glucose homeostasis by a dual mechanism involving induction of PGC1α and dephosphorylation of FoxO1
Authors: Bernsmeier C. , Calabrese D. , Heim M. H. , Duong H. T. F.
Published: November 2013

The maintenance of glucose homeostasis is a complex process in which the insulin signalling pathway plays a major role. Disruption of insulin‐regulated glucose homeostasis is frequently observed in chronic hepatitis C (CHC) infection and might potentially contribute to type 2 diabetes mellitus (T2DM) development. Presently, the mechanism that links HCV infection to insulin resistance remains unclear. Previously, we have reported that HCV protein expression in HCV transgenic mice (B6HCV) leads to an overexpression of protein phosphatase 2A (PP2A) through an ER stress response. In the present work, we describe an association of FoxO1 hypophosphorylation and upregulation of both PGC‐1α and G6Pase to phenotypic hyperglycaemia and insulin resistance in B6HCV mice. In vitro, we observed that PGC1α is concomitantly induced with PP2A. Moreover, we show that the enhanced PP2A expression is sufficient to inhibit insulin‐induced FoxO1 phosphorylation via blockade of insulin‐mediated Akt activation or/and through direct association and dephosphorylation of pS‐FoxO1. Consequently, we found that the gluconeogenic gene glucose‐6‐phosphatase is upregulated. These observations were confirmed in liver biopsies obtained from CHC patients. In summary, our results show that HCV‐mediated upregulation of PP2A catalytic subunit alters signalling pathways that control hepatic glucose homeostasis by inhibiting Akt and dephosphorylation of FoxO1.
Using financial incentives to increase fruit and vegetable consumption in the UK
Authors: Betty A. L.
Published: November 2013

Encouraging the consumption of fruits and vegetables can help people increase their intake of micronutrients, dietary fibre and non‐nutrient substances, which together have benefits for health. A high intake of fruits and vegetables is associated with a lower risk of a number of diseases including heart disease, stroke, type 2 diabetes and some cancers. Among the numerous barriers to purchasing fruits and vegetables, price is still cited as a common factor. Therefore, more needs to be done to incentivise consumers to pick up more of these foods during their weekly shop.

The UK Public Health Responsibility Deal seeks to reshape the food environment through behaviour change interventions; however, evidence to support the effectiveness of altering environments to change behaviour as a means to improve population health is weak. In particular, reducing price is a frequently considered policy to improve dietary habits. However, few studies to date have evaluated the effectiveness of such interventions on encouraging fruit and vegetable consumption.

Our goal (The Co‐operative Group), in line with the Public Health Responsibility Deal, is to do more to create a positive environment that supports and enables people to increase their fruit and vegetable consumption. In light of this, we piloted a coupon incentive scheme in July 2012 for low fruit and vegetable spenders to see if making these items more affordable would encourage purchases and facilitate increased consumption. Results showed that sales of fruits and vegetables increased by 23.2% during the four‐week campaign, with 132 000 redemptions of the coupon by 90 000 members.
The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin
Authors: Pustovit R. V. , Callaghan B. , Kosari S. , Rivera L. R. , Thomas H. , Brock J. A. , Furness J. B.
Published: November 2013

Background

Discovery of adequate pharmacological treatments for constipation has proven elusive. Increased numbers of bowel movements were reported as a side‐effect of ulimorelin treatment of gastroparesis, but there has been no investigation of the site of action.

Methods

Anesthetized rats were used to investigate sites and mechanisms of action of ulimorelin.

Key Results

Intravenous ulimorelin (1–5 mg/kg) caused a substantial and prolonged (~1 h) increase in colorectal propulsive activity and expulsion of colonic contents. This was prevented by cutting the nerves emerging from the lumbosacral cord, by the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin receptor. The effect of intravenous ulimorelin was mimicked by direct application of ulimorelin (5 μg) to the lumbosacral spinal cord.

Conclusions & Inferences

Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. Its effects are long‐lasting, in contrast with other colokinetics that target ghrelin receptors.
Caterpillar attack triggers accumulation of the toxic maize protein RIP2
Authors: Chuang Wen‐Po , Herde Marco , Ray Swayamjit , Castano‐Duque Lina , Howe Gregg A. , Luthe Dawn S.
Published: November 2013

Some plant‐derived anti‐herbivore defensive proteins are induced by insect feeding, resist digestion in the caterpillar gut and are eliminated in the frass. We have identified several maize proteins in fall armyworm (Spodoptera frugiperda) frass that potentially play a role in herbivore defense. Furthermore, the toxicity of one of these proteins, ribosome‐inactivating protein 2 (RIP2), was assessed and factors regulating its accumulation were determined.

To understand factors regulating RIP2 protein accumulation, maize (Zea mays) plants were infested with fall armyworm larvae or treated with exogenous hormones. The toxicity of recombinant RIP2 protein against fall armyworm was tested.

The results show that RIP2 protein is synthesized as an inactive proenzyme that can be processed in the caterpillar gut. Also, caterpillar feeding, but not mechanical wounding, induced foliar RIP2 protein accumulation. Quantitative real‐time PCR indicated that RIP2 transcripts were rapidly induced (1 h) and immunoblot analysis indicated that RIP2 protein accumulated soon after attack and was present in the leaf for up to 4 d after caterpillar removal. Several phytohormones, including methyl jasmonate, ethylene, and abscisic acid, regulated RIP2 protein expression. Furthermore, bioassays of purified recombinant RIP2 protein against fall armyworm significantly retarded caterpillar growth.

We conclude that the toxic protein RIP2 is induced by caterpillar feeding and is one of a potential suite of proteins that defend maize against chewing herbivores.
On the Importance of the First Observation in GLS Detrending in Unit Root Testing
Authors: Westerlund Joakim
Published: November 2013

First‐differencing is generally taken to imply the loss of one observation, the first, or at least that the effect of ignoring this observation is asymptotically negligible. However, this is not always true, as in the case of generalized least squares (GLS) detrending. In order to illustrate this, the current article considers as an example the use of GLS detrended data when testing for a unit root. The results show that the treatment of the first observation is absolutely crucial for test performance, and that ignorance causes test break‐down.
Enzyme Activity and Structural Dynamics Linked to Micelle Formation: A Fluorescence Anisotropy and ESR Study
Authors: Chin Michael , Somasundaran Ponisseril
Published: November 2013

Activities of the enzymes, protease subtilisin and horse radish peroxidase (HRP) have been increased 50 and 40%, respectively, in the presence of the nonionic surfactant, alkyl polyglucoside, compared with the activities in buffer alone. This enzyme hyperactivity reaches a peak at 3.0 mm of surfactant. Investigation into the structure of surfactant aggregates indicates “giant” micelle superstructures at this range of surfactant concentration of 1.7 μm in diameter—dramatically decreasing to 60 and 70 nm at higher surfactant concentrations, while surface tension measurements indicate two critical micelle concentration inflection points at 0.2 and 5.0 mm, which suggests transitions in micelle structure with respect to concentration. Furthermore, electron spin resonance (ESR) indicates that the micelles in first critical micelle concentration regime are loosely packed relative to the second aggregate phase. We hypothesize that this loose packing results in diminished hydration shell repulsion between the micelles, leading to the large, micrometer‐sized aggregates. We further hypothesize that it is the interaction with these loosely packed micelles that affects the flexibility of the HRP and protease enzyme structure. Time‐resolved fluorescence anisotropy of subtilisin in Brij‐30 indicates increasing flexibility of catalytic active site with surfactant concentration. This is correlated with an increase in enzymatic activity.
Singlet Oxygen Generation by Cyclometalated Complexes and Applications
Authors: Ashen‐Garry David , Selke Matthias
Published: November 2013

While cyclometalated complexes have been extensively studied for optoelectronic applications, these compounds also represent a relatively new class of photosensitizers for the production of singlet oxygen. Thus far, singlet oxygen generation from cyclometalated Ir and Pt complexes has been studied in detail. In this review, photophysical data for singlet oxygen generation from these complexes are presented, and the mechanism of 1O2 generation is discussed, including evidence for singlet oxygen generation via an electron‐transfer mechanism for some of cyclometalated Ir complexes. The period from the first report of singlet oxygen generation by a cyclometalated Ir complex in 2002 through August 2013 is covered in this review. This new class of singlet oxygen photosensitizers may prove to be rather versatile due to the ease of substitution of ancillary ligands without loss of activity. Several cyclometalated complexes have been tethered to zeolites, polystyrene, or quantum dots. Applications for photooxygenation of organic molecules, including “traditional” singlet oxygen reactions (ene reaction, [4 + 2] and [2 + 2] cycloadditions) as well as oxidative coupling of amines are presented. Potential biomedical applications are also reviewed.