bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐Neglect in an Elderly Community‐Dwelling U.S. Chinese Population: Findings from the Population Study of Chinese Elderly in Chicago Study
Authors: Dong XinQi
Published: November 2014

This study aimed to examine the prevalence of self‐neglect and its specific behaviors in an elderly community‐dwelling U.S. Chinese population through a population‐based cohort study (PINE Study) in the greater Chicago area. Community‐dwelling population of older Chinese adults were interviewed from 2011 to 2013 (n = 3,159). The personal and home environment of participants was rated based on prevalence of hoarding behavior, personal hygiene, repairs needed on the home, sanitary condition of the home, and adequacy of utilities. Prevalence estimates were presented according to self‐reported quality of life (QOL). It was found that the prevalence of self‐neglect was 18.2% for mild self‐neglect and 10.9% for moderate to severe self‐neglect. Unsanitary conditions (17.0%) was the most prevalent, followed by need for home repair (16.3%), hoarding behavior (14.9%), poor personal hygiene (11.3%), and inadequate utilities (4.2%). The prevalence of elder self‐neglect of all severities and of all types was higher in older adults with fair or poor QOL than in those with good or very good QOL. Poorer QOL was significantly associated with greater risk of self‐neglect of all severities (mild self‐neglect: odds ratio (OR) = 1.93, 95% confidence interval (CI) = 1.26–2.96, P < .001; moderate to severe self‐neglect: OR = 3.58, 95% CI = 1.79–7.13, P < .001) and specific personal and environmental hazards. The study's authors conclude that elder self‐neglect is prevalent, especially in elderly adults with poorer QOL. Future research is needed to examine risk and protective factors associated with elder self‐neglect.
Shared Medical Appointments to Screen for Geriatric Syndromes: Preliminary Data from a Quality Improvement Initiative
Authors: May Suepattra G. , Cheng Peter H. , Tietbohl Caroline K. , Trujillo Laurel , Reilly Kelly , Frosch Dominick L. , Lin Grace A.
Published: November 2014

Older adults are at greater risk of developing conditions that affect health outcomes, quality of life, and costs of care. Screening for geriatric conditions such as memory loss, fall risk, and depression may contribute to the prevention of adverse physical and mental comorbidities, unnecessary hospitalizations, and premature nursing home admissions. Because screening is not consistently performed in primary care settings, a shared medical appointment (SMA) program was developed to fill this gap in care. The goals of the program were to improve early identification of at‐risk individuals and ensure appropriate follow‐up for memory loss, fall risk, and depression; facilitate discussion about prevention, diagnosis, and treatment of these conditions; implement strategies to reduce risks for these conditions; and increase access to screening and expand preventive health services for older adults. Between August 2011 and May 2013, 136 individuals aged 60 and older participated in the program. Three case studies highlighting the psychosocial and physiological findings of participation in the program are presented. Preliminary data suggest that SMAs are an effective model of regularly screening at‐risk older adults that augments primary care practice by facilitating early detection and referral for syndromes that may otherwise be missed or delayed.
Gingival crevicular fluid proteomes in health, gingivitis and chronic periodontitis
Authors: Huynh A. H. S. , Veith P. D. , McGregor N. R. , Adams G. G. , Chen D. , Reynolds E. C. , Ngo L. H. , Darby I. B.
Published: November 2014

Objective

The aim of this study was to compare the proteome composition of gingival crevicular fluid obtained from healthy periodontium, gingivitis and chronic periodontitis affected sites.

Background

Owing to its site‐specific nature, gingival crevicular fluid is ideal for studying biological processes that occur during periodontal health and disease progression. However, few studies have been conducted into the gingival crevicular fluid proteome due to the small volumes obtained.

Methods

Fifteen males were chosen for each of three different groups, healthy periodontium, gingivitis and chronic periodontitis. They were categorized based on clinical measurements including probing depth, bleeding on probing, plaque index, radiographic bone level, modified gingival index and smoking status. Gingival crevicular fluid was collected from each patient, pooled into healthy, gingivitis and chronic periodontitis groups and their proteome analyzed by gel electrophoresis and liquid chromatography electrospray ionization ion trap tandem mass spectrometry.

Results

One hundred and twenty‐one proteins in total were identified, and two‐thirds of these were identified in all three conditions. Forty‐two proteins were considered to have changed in abundance. Of note, cystatin B and cystatin S decreased in abundance from health to gingivitis and further in chronic periodontitis. Complement proteins demonstrated an increase from health to gingivitis followed by a decrease in chronic periodontitis. Immunoglobulins, keratin proteins, fibronectin, lactotransferrin precursor, 14‐3‐3 protein zeta/delta, neutrophil defensin 3 and alpha‐actinin exhibited fluctuations in levels.

Conclusion

The gingival crevicular fluid proteome in each clinical condition was different and its analysis may assist us in understanding periodontal pathogenesis.
Regulation of adrenomedullin and nitric oxide production by periodontal bacteria
Authors: Hussain Q. A. , McKay I. J. , Gonzales‐Marin C. , Allaker R. P.
Published: November 2014

Objectives

In periodontitis the host response to bacterial challenge includes activity of the multifunctional molecules adrenomedullin (AM) and nitric oxide (NO). The aim of this study was to investigate the role of periodontal bacteria in regulating the production of these molecules from cultured cells.

Material and Methods

Regulation of AM and NO production from oral keratinocytes when challenged with culture supernatants from Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Veillonella atypica, Streptococcus salivarius and Candida albicans was examined. AM and NO were measured in cell culture supernatants using an enzyme‐linked immunosorbent assay and the nitrate/nitrite (NO metabolites) Griess assay respectively. Cellular production of AM and inducible NO synthase was also analysed in target cells by immunofluorescence and Western blot analysis. The inter‐relationship of AM and NO production were further investigated with macrophages.

Results

A. actinomycetemcomitans and C. rectus induced maximal levels of both AM and NO after 6 and 48 h respectively from oral keratinocytes. AM production in macrophages was upregulated in response to the NO donor S‐nitrosoglutathione and partially blocked by the inducible NO synthase inhibitor, Nω‐Nitro‐l‐arginine methyl ester hydrochloride. Likewise, NO production was increased upon exposure to AM, while the AM receptor antagonist AM 22‐52 reduced the release of NO.

Conclusions

Pathogens associated with aggressive periodontitis, A. actinomycetemcomitans and C. rectus, were more effective than those associated with chronic periodontitis, P. gingivalis and Prev. intermedia, and commensals, S. salivarius and V. atypica, as regards the upregulation of AM and NO production from oral keratinocytes. Interaction between these molecules was also demonstrated with macrophages. Understanding the coordinated regulation of AM and NO production in response to periodontal bacteria may identify ways to promote their protective effects and minimize destructive potential.
Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma
Authors: Kolligs Frank T. , Bilbao Jose I. , Jakobs Tobias , Iñarrairaegui Mercedes , Nagel Jutta M. , Rodriguez Macarena , Haug Alexander , D'Avola Delia , op den Winkel Mark , Martinez‐Cuesta Antonio , Trumm Christoph , Benito Alberto , Tatsch Klaus , Zech Christoph J. , Hoffmann Ralf‐Thorsten , Sangro Bruno
Published: November 2014

Background & Aims

To compare selective internal radiation therapy (SIRT) with transarterial chemoembolization (TACE), the standard‐of‐care for intermediate‐stage unresectable, hepatocellular carcinoma (HCC), as first‐line treatment.

Methods

SIRTACE was an open‐label multicenter randomized‐controlled pilot study, which prospectively compared primarily safety and health‐related quality of life (HRQoL) changes following TACE and SIRT. Patients with unresectable HCC, Child‐Pugh ≤B7, ECOG performance status ≤2 and ≤5 liver lesions (≤20 cm total maximum diameter) without extrahepatic spread were randomized to receive either TACE (at 6‐weekly intervals until tumour enhancement was not observed on MRI or disease progression) or single‐session SIRT (yttrium‐90 resin microspheres).

Results

Twenty‐eight patients with BCLC stage A (32.1%), B (46.4%) or C (21.4%) received either a mean of 3.4 (median 2) TACE interventions (N = 15) or single SIRT (N = 13). Both treatments were well tolerated. Despite SIRT patients having significantly worse physical functioning at baseline, at week‐12, neither treatment had a significantly different impact on HRQoL as measured by Functional Assessment of Cancer Therapy‐Hepatobiliary total or its subscales. Both TACE and SIRT were effective for the local control of liver tumours. Best overall response‐rate (RECIST 1.0) of target lesions were 13.3% and 30.8%, disease control rates were 73.3% and 76.9% for TACE and SIRT, respectively. Two patients in each group were down‐staged for liver transplantation (N = 3) or radiofrequency ablation (N = 1).

Conclusions

Single‐session SIRT appeared to be as safe and had a similar impact on HRQoL as multiple sessions of TACE, suggesting that SIRT might be an alternative option for patients eligible for TACE.
Prognostic role of magnetic resonance imaging vs. computed tomography for hepatocellular carcinoma undergoing chemoembolization
Authors: Kim Beom Kyung , Kim Kyung Ah , An Chansik , Yoo Eun Jin , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Han Kwang‐Hyub , Kim Seung Up , Kim Myeong‐Jin
Published: November 2014

Background & Aims

Computed tomography (CT) and magnetic resonance imaging (MRI) play important roles in diagnosis and staging of hepatocellular carcinoma (HCC). However, prognostic roles of radiological characteristics are not yet determined.

Methods

Eighty‐eight patients treated with chemoembolization were analysed. Radiological parameters at baseline were assessed in all patients using both dynamic CT and MRI. Treatment responses were assessed using modified RECIST 4 weeks after the first chemoembolization.

Results

Gross vascular invasion (GVI), bile duct invasion, irregular tumour margin (ITM), peripheral ragged enhancement (PRE) and satellite nodules on CT or MRI were associated with non‐response (stable disease or progression) after chemoembolization respectively (all P ≤ 0.05). GVI, ITM and PRE on CT or MRI were also independently associated with poor overall survival (OS) respectively (all P ≤ 0.05). Using these results, a prognostic scoring system for CT and MRI were developed; 0, absence of all three features (GVI, ITM and PRE); 1, presence of one feature; 2, presence of two features; and 3, presence of three features. After adjusting tumour size, tumour number and alpha‐foetoprotein level, both CT and MRI scores were independently associated with OS (both P < 0.001). Patients with CT or MRI score ≥2 had a worse OS than those with score <2 (adjusted hazard ratios, 3.837 and 2.938 respectively). MRI‐specific parameters such as signal intensity on T2‐ or T1‐weighted images, fat signal or hyperintensity on diffusion‐weighted images did not have prognostic value (all P > 0.05).

Conclusions

Radiological parameters by CT and MRI may be useful in biological characterization of tumours and prognostification for HCC treated with chemoembolization.
The distribution of genetic variance across phenotypic space and the response to selection
Authors: Blows Mark W. , McGuigan Katrina
Published: November 2014

The role of adaptation in biological invasions will depend on the availability of genetic variation for traits under selection in the new environment. Although genetic variation is present for most traits in most populations, selection is expected to act on combinations of traits, not individual traits in isolation. The distribution of genetic variance across trait combinations can be characterized by the empirical spectral distribution of the genetic variance–covariance (G) matrix. Empirical spectral distributions of G from a range of trait types and taxa all exhibit a characteristic shape; some trait combinations have large levels of genetic variance, while others have very little genetic variance. In this study, we review what is known about the empirical spectral distribution of G and show how it predicts the response to selection across phenotypic space. In particular, trait combinations that form a nearly null genetic subspace with little genetic variance respond only inconsistently to selection. We go on to set out a framework for understanding how the empirical spectral distribution of G may differ from the random expectations that have been developed under random matrix theory (RMT). Using a data set containing a large number of gene expression traits, we illustrate how hypotheses concerning the distribution of multivariate genetic variance can be tested using RMT methods. We suggest that the relative alignment between novel selection pressures during invasion and the nearly null genetic subspace is likely to be an important component of the success or failure of invasion, and for the likelihood of rapid adaptation in small populations in general.
Life‐stage differences in spatial genetic structure in an irruptive forest insect: implications for dispersal and spatial synchrony
Authors: James Patrick M. A. , Cooke Barry , Brunet Bryan M. T. , Lumley Lisa M. , Sperling Felix A. H. , Fortin Marie‐Josée , Quinn Vanessa S. , Sturtevant Brian R.
Published: November 2014

Dispersal determines the flux of individuals, energy and information and is therefore a key determinant of ecological and evolutionary dynamics. Yet, it remains difficult to quantify its importance relative to other factors. This is particularly true in cyclic populations in which demography, drift and dispersal contribute to spatio‐temporal variability in genetic structure. Improved understanding of how dispersal influences spatial genetic structure is needed to disentangle the multiple processes that give rise to spatial synchrony in irruptive species. In this study, we examined spatial genetic structure in an economically important irruptive forest insect, the spruce budworm (Choristoneura fumiferana) to better characterize how dispersal, demography and ecological context interact to influence spatial synchrony in a localized outbreak. We characterized spatial variation in microsatellite allele frequencies using 231 individuals and seven geographic locations. We show that (i) gene flow among populations is likely very high (Fst ≈ 0); (ii) despite an overall low level of genetic structure, important differences exist between adult (moth) and juvenile (larvae) life stages; and (iii) the localized outbreak is the likely source of moths captured elsewhere in our study area. This study demonstrates the potential of using molecular methods to distinguish residents from migrants and for understanding how dispersal contributes to spatial synchronization. In irruptive populations, the strength of genetic structure depends on the timing of data collection (e.g. trough vs. peak), location and dispersal. Taking into account this ecological context allows us to make more general characterizations of how dispersal can affect spatial synchrony in irruptive populations.
Comparative genomics in the Asteraceae reveals little evidence for parallel evolutionary change in invasive taxa
Authors: Hodgins Kathryn A. , Bock Dan G. , Hahn Min A. , Heredia Sylvia M. , Turner Kathryn G. , Rieseberg Loren H.
Published: November 2014

Asteraceae, the largest family of flowering plants, has given rise to many notorious invasive species. Using publicly available transcriptome assemblies from 35 Asteraceae, including six major invasive species, we examined evidence for micro‐ and macro‐evolutionary genomic changes associated with invasion. To detect episodes of positive selection repeated across multiple introductions, we conducted comparisons between native and introduced genotypes from six focal species and identified genes with elevated rates of amino acid change (dN/dS). We then looked for evidence of positive selection at a broader phylogenetic scale across all taxa. As invasive species may experience founder events during colonization and spread, we also looked for evidence of increased genetic load in introduced genotypes. We rarely found evidence for parallel changes in orthologous genes in the intraspecific comparisons, but in some cases we identified changes in members of the same gene family. Using among‐species comparisons, we detected positive selection in 0.003–0.69% and 2.4–7.8% of the genes using site and stochastic branch‐site models, respectively. These genes had diverse putative functions, including defence response, stress response and herbicide resistance, although there was no clear pattern in the GO terms. There was no indication that introduced genotypes have a higher proportion of deleterious alleles than native genotypes in the six focal species, suggesting multiple introductions and admixture mitigated the impact of drift. Our findings provide little evidence for common genomic responses in invasive taxa of the Asteraceae and hence suggest that multiple evolutionary pathways may lead to adaptation during introduction and spread in these species.
The development and validation of a psychological questionnaire for patients undergoing orthognathic treatment
Authors: Shelton A. T. , Houghton N. Y. , Morris D. O. , Latchford G. L. , Bekker H. L. , Munyombwe T.
Published: November 2014

Structured Abstract

Objectives

To develop a questionnaire to assess the psychosocial aspects which orthognathic patients considered important regarding their dento‐facial deformity.

Setting and sample population

A multicentre, prospective, questionnaire development and validation study based in the UK.

Material and methods

Questionnaire development involved item (question) selection through literature review, consultation and feedback from a questionnaire development group and semi‐structured interviews. A ‘final’ questionnaire was tested on a cross‐sectional sample of 110 pre‐operative and 74 post‐operative orthognathic patients and a longitudinal sample of 23 orthognathic patients. Validity was tested using Rasch analysis.

Results

Reliability for the Hospital Anxiety and Depression Scale (HADS) section was unsatisfactory (ICC = 0.232–0.829, Cronbach alpha = 0.625–0.670), but for the well‐ being (ICC = 0.857, Cronbach alpha = 0.827–0.895) and expectations (ICC = 0.861, Cronbach alpha = 0.804–0.882) sections were satisfactory. The well‐being section was the only section found to be valid for the pre‐and post‐operative samples. Responsiveness was satisfactory for the well‐being scale (p = 0.001).

Conclusions

A new condition‐specific orthognathic questionnaire has been developed which has been shown to be reliable, valid and responsive for the well‐being scale. The HADS, as tested by Rasch analysis, was found not to be valid for this orthognathic population.
The eco‐evolutionary consequences of interspecific phenological asynchrony – a theoretical perspective
Authors: Johansson Jacob , Kristensen Nadiah P. , Nilsson Jan‐Åke , Jonzén Niclas
Published: November 2014

The timing of biological events (phenology) is an important aspect of both a species’ life cycle and how it interacts with other species and its environment. Patterns of phenological change have been given much scientific attention, particularly recently in relation to climate change. For pairs of interacting species, if their rates of phenological change differ, then this may lead to asynchrony between them and disruption of their ecological interactions. However it is often difficult to interpret differential rates of phenological change and to predict their ecological and evolutionary consequences. We review theoretical results regarding this topic, with special emphasis on those arising from life history theory, evolutionary game theory and population dynamic models. Much ecological research on phenological change builds upon the concept of match/mismatch, so we start by putting forward a simple but general model that captures essential elements of this concept. We then systematically compare the predictions of this baseline model with expectations from theory in which additional ecological mechanisms and features of species life cycles are taken into account. We discuss the ways in which the fitness consequences of interspecific phenological asynchrony may be weak, strong, or idiosyncratic. We discuss theory showing that synchrony is not necessarily an expected evolutionary outcome, and how population densities are not necessarily maximized by adaptation, and the implications of these findings. By bringing together theoretical developments regarding the eco‐evolutionary consequences of phenological asynchrony, we provide an overview of available alternative hypotheses for interpreting empirical patterns as well as the starting point for the next generation of theory in this field.
Semi‐automated kinetic perimetry provides additional information to static automated perimetry in the assessment of the remaining visual field in end‐stage glaucoma
Authors: Nowomiejska Katarzyna , Wrobel‐Dudzinska Dominika , Ksiazek Katarzyna , Ksiazek Piotr , Rejdak Konrad , Maciejewski Ryszard , Juenemann Anselm G , Rejdak Robert
Published: November 2014

Purpose

To test the hypothesis whether semi‐automated kinetic perimetry (SKP) provides additional information to static automated perimetry (SAP) in the assessment of the remaining visual field in end‐stage glaucoma, as defined by disc appearance (cup‐to‐disc ratio worse than 0.9) and SAP criteria (MD worse than 20 dB).

Methods

Fifty eyes of 44 patients presenting with end‐stage glaucoma were examined first with SAP within the central 30° using stimulus size III, followed by SKP within 90° using test targets III4e and V4e.

Results

Overall, SKP provided additional information over SAP in more than half (54%) of the cases. In 16 instances (32%), SKP revealed visual field island beyond 30° that was undetected by SAP. In eight cases (16%), SKP showed both a central island and peripheral island of visual field. In three cases (6%) altitudinal scotomatous loss was found using SKP, but not in SAP. In 23 cases (46%) the central visual field island was defined both with SAP and SKP. The mean examination duration was 4 min for SAP and 9 min for SKP.

Conclusions

In clinical practice, SKP with III4e and V4e test targets provides more information than 30° SAP regarding the remaining peripheral VF in patients with end‐stage glaucoma; however, a longer test time is required for SKP.
Evaluation of the relative roles of global versus local sedimentary controls on Middle to Late Pleistocene formation of continental margin strata, Canterbury Basin, New Zealand
Authors: Villaseñor Tania , Jaeger John M. , Marsaglia Kathleen M. , Browne Greg H.
Published: November 2014

Determining the relative influence of eustasy versus local sedimentary processes on strata formation is a fundamental challenge in the study of continental margin stratigraphy. In this paper, the relative contribution of these factors on continental margin evolution during the Middle to Late Pleistocene is evaluated using samples from Integrated Ocean Drilling Program Expedition 317. Core‐logging, biostratigraphy and quantitative X‐ray diffraction mineralogy are used to delineate continental shelf sedimentary systems. Major lithological unconformities bound stratigraphic sequences that contain recurring compositional patterns and that resemble other examples of Middle to Upper Pleistocene sequences. However, a preliminary chronology suggests that sequence boundary formation cannot be linked ‘one to one’ with eustatic cycles and therefore these sequences can contain multiple ca 100 ka eustatic cycles. Smaller amplitude, higher frequency transitions in sediment composition are interpreted as stratigraphic sequences driven by more rapid perturbations in the interplay of accommodation and sediment supply; their stratigraphy is variable in time and across the shelf, suggesting a strong influence of local sedimentary forcing in their formation. Changes in sediment composition after the Middle Pleistocene Transition indicate that sediment transfer from onshore sources in the glaciated Southern Alps to the middle‐shelf occurred over a single 100 ka glacio‐eustatic cycle, with an additional 100 ka lag before the mineralogical signal was preserved on the outer‐shelf. This phenomenon is coincident with rapid shelf progradation in this basin, suggesting a causal relation between across‐shelf sediment transport and margin progradation. This is one of very few studies that provide insights at the core scale into the processes driving continental margin evolution during the Middle to Late Pleistocene. This work shows that compositional changes in mud‐dominated successions can lead to a sequence stratigraphic interpretation and the identification of high‐frequency sequences, which may not be possible using a conventional stratigraphic approach.
Platelet Factor 4 Limits Th17 Differentiation and Ischaemia–Reperfusion Injury After Liver Transplantation in Mice
Authors: Guo H. , Wang Y. , Zhao Z. , Shao X.
Published: November 2014

Liver ischaemia/reperfusion injury (IRI) is a serious pathologic process encountered in a number of clinical syndromes including liver transplantation, liver resection, trauma and haemorrhagic shock. Platelet factor 4 (PF4) was the first discovered CXC chemokine and is found in platelet granules at very high concentration. In this study, we provide strong evidence that PF4 is involved directly in liver innate immune response against IRI by regulating Th17 differentiation. PF4 deficiency aggravates liver IRI, as shown by higher serum alanine aminotransferase (ALT) levels and Suzuki scores. PF4 deficiency promotes Th17 response with higher levels of IL‐23, IL‐6 and IL‐17, which aggravates liver IRI. Furthermore, PF4 deficiency limits suppressor of cytokine signalling 3 (SOCS3) expressions, and PF4 fails to suppress expression of IL‐17 in cells transfected with SOCS3 SiRNA. In conclusion, PF4 limits liver IRI through IL‐17 inhibition via upregulation of SOCS3.
Placental Transfer of IgG Antibodies Specific to Klebsiella and Pseudomonas LPS and to Group B Streptococcus in Twin Pregnancies
Authors: Stach S. C. L. , Brizot M. L. , Liao A. W. , Palmeira P. , Francisco R. P. V. , Carneiro‐Sampaio M. M. S. , Zugaib M.
Published: November 2014

Group B Streptococcus (GBS), Klebsiella spp. and Pseudomonas spp. are important aetiological agents of neonatal infections in Brazil. There is a lack of data in the literature regarding the specific transport of immunoglobulin G (IgG) against these pathogens in multiple pregnancies. Maternal (n = 55) and umbilical cord (n = 110) blood samples were prospectively collected at birth from 55 twin pregnancies. The factors associated with cord levels and transfer ratios of IgG against GBS, Klebsiella and Pseudomonas were examined. The IgG umbilical cord serum levels specific to GBS, Klebsiella LPS and Pseudomonas LPS were significantly associated with maternal‐specific IgG concentrations and the presence of diabetes. The anti‐Klebsiella IgG cord serum concentrations were also related to birthweight and the presence of hypertension. The transfer ratios against GBS and Pseudomonas LPS were associated with maternal‐specific IgG concentrations. The transfer ratios for GBS and Pseudomonas LPS were associated with gestational age at delivery and the presence of diabetes, respectively. None of the examined parameters were related to Klebsiella LPS transfer ratios. We conclude that in twin pregnancies, specific maternal IgG serum concentrations and diabetes were the parameters associated with umbilical cord serum IgG concentrations reactive with the three pathogens investigated. All the other parameters investigated showed different associations with neonatal‐specific IgG levels according to the antigen studied. There was no uniformity of the investigated parameters regarding association with placental IgG transfer ratios against the GBS, Pseudomonas LPS and Klebsiella LPS.
Narrating Sustainability in Canadian Health Care Reform Discourse
Authors: Bhatia Vandna , Orsini Michael
Published: November 2014

In Canada, as in other industrialized welfare states, definitions of health system sustainability reflect different goals and correspondingly diverse ways of understanding exactly what is to be sustained and how. In this article, we report on results from a survey of documents and groups involved in and/or concerned about sustainability of the healthcare system. We identify four broad narratives of sustainability in Canadian healthcare reform discourse, and explore what these different sustainability narratives tell us about the character and contours of these often‐fractious debates. We argue that sustainability itself may not be a paradigm shift, as has been suggested, but a plot device that helps to steer the story in a particular direction, ‘black‐boxing’ certain aspects of context and emphasizing others.
Quantitative polymerase chain reaction for detection of human herpesvirus‐7 infection in umbilical cord blood donors
Authors: Abedi E. , Kheirandish M. , Sharifi Z. , Samiee S. , Kokhaei P. , Pourpak Z. , Ashraf M.J.
Published: November 2014

Objective

Umbilical cord blood (UCB) has been a reasonable alternative to granulocyte colony‐stimulating factor‐mobilized peripheral blood or bone marrow, as a source of hematopoietic stem cells with a lower risk of graft‐versus‐host disease. In immunocompromised hosts after transplantation, the risk of viral infection in adults, especially with beta‐herpesviruses such as human herpesvirus‐7 (HHV‐7), may be increased. This virus in immunocompromised patients can be reactivated from latency and converted to an active phase. Therefore, light‐upon‐extension real‐time polymerase chain reaction (PCR) was developed to assess the prevalence and load of HHV‐7 in the plasma and buffy coat of donors.

Methods

About 825 UCB samples under standard protocol from donors were collected. Then, DNA from plasma and buffy coat was extracted and quantitative real‐time PCR was performed with light‐upon‐extension primers.

Results

Overall, HHV‐7 was detected in 3.64% (30/825) of UCB donors. HHV‐7 DNA was detected in 26 (3.2%) buffy coat samples (latent infection), and only 4 (0.48%) of them were positive for HHV‐7 DNA in plasma samples (active infection); the mean HHV‐7 viral load was 1.31 × 101 copies/mL in latent infection, and 1.94 × 105 copies/mL in active infection.

Conclusions

We suggest that real‐time PCR in plasma and buffy coat could be a useful method to detect active and latent HHV‐7 infection in UCB donors and determine its role in subsequent transmission events.
Atorvastatin reduces T‐cell activation and exhaustion among HIV‐infected cART‐treated suboptimal immune responders in Uganda: a randomised crossover placebo‐controlled trial
Authors: Nakanjako Damalie , Ssinabulya Isaac , Nabatanzi Rose , Bayigga Lois , Kiragga Agnes , Joloba Moses , Kaleebu Pontiano , Kambugu Andrew D. , Kamya Moses R. , Sekaly Rafick , Elliott Alison , Mayanja‐Kizza Harriet
Published: November 2014

Objective

T‐cell activation independently predicts mortality, poor immune recovery and non‐AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti‐immune activation effects among HIV‐infected cART‐naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T‐cell activation among cART‐treated adults with suboptimal immune recovery.

Methods

A randomised double‐blind placebo‐controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T‐cell activation (CD3 + CD4 + /CD8 +  CD38 + HLADR+) and in T‐cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry.

Results

Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T‐cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8‐T‐cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T‐cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T‐cell exhaustion (27% vs. 16%), P = 0.004. There was no carry‐over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported.

Conclusion

Atorvastatin reduced T‐cell immune activation and exhaustion among cART‐treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub‐Saharan Africa.
PRL1 modulates root stem cell niche activity and meristem size through WOX5 and PLTs in Arabidopsis
Authors: Ji Hongtao , Wang Shuangfeng , Li Kexue , Szakonyi Dóra , Koncz Csaba , Li Xia
Published: November 2014

The stem cell niche in the root meristem maintains pluripotent stem cells to ensure a constant supply of cells for root growth. Despite extensive progress, the molecular mechanisms through which root stem cell fates and stem cell niche activity are determined remain largely unknown. In Arabidopsis thaliana, the Pleiotropic Regulatory Locus 1 (PRL1) encodes a WD40‐repeat protein subunit of the spliceosome‐activating Nineteen Complex (NTC) that plays a role in multiple stress, hormone and developmental signaling pathways. Here, we show that PRL1 is involved in the control of root meristem size and root stem cell niche activity. PRL1 is strongly expressed in the root meristem and its loss of function mutation results in disorganization of the quiescent center (QC), premature stem cell differentiation, aberrant cell division, and reduced root meristem size. Our genetic studies indicate that PRL1 is required for confined expression of the homeodomain transcription factor WOX5 in the QC and acts upstream of the transcription factor PLETHORA (PLT) in modulating stem cell niche activity and root meristem size. These findings define a role for PRL1 as an important determinant of PLT signaling that modulates maintenance of the stem cell niche and root meristem size.
Peripheral chemoreceptors and cardiorespiratory coupling: a link to sympatho‐excitation
Authors: Zoccal Daniel B.
Published: November 2014

New Findings

What is the topic of this review?

Chronic intermittent hypoxia (CIH), as observed in patients with obstructive sleep apnoea, is associated with the development of sympathetically mediated arterial hypertension. Nevertheless, the mechanisms underpinning the augmented sympathetic outflow in CIH still remain under investigation.

What advances does it highlight?

In this report, I present experimental evidence supporting the hypothesis that changes in the function of the respiratory network and coupling with the sympathetic nervous system may be considered as a novel and relevant mechanism for the increase in baseline sympathetic outflow in animals submitted to CIH.

Chronic intermittent hypoxia (CIH) has been identified as a relevant risk factor for the development of enhanced sympathetic outflow and arterial hypertension. Several studies have highlighted the importance of peripheral chemoreceptors for the cardiovascular changes elicited by CIH. However, the effects of CIH on the central mechanisms regulating sympathetic outflow are not fully elucidated. Our research group has explored the hypothesis that the enhanced sympathetic drive following CIH exposure is, at least in part, dependent on alterations in the respiratory network and its interaction with the sympathetic nervous system. In this report, I discuss the changes in the discharge profile of baseline sympathetic activity in rats exposed to CIH, their association with the generation of active expiration and the interactions between expiratory and sympathetic neurones after CIH conditioning. Together, these findings are consistent with the theory that mechanisms of central respiratory–sympathetic coupling are a novel factor in the development of neurogenic hypertension.
Short‐latency inhibitory reflex responses to inspiratory loading of the scalene muscles are impaired in spinal cord injury
Authors: McBain Rachel A. , Hudson Anna L. , Gandevia Simon C. , Butler Jane E.
Published: November 2014

New Findings

What is the central question of this study?

The aim was to determine whether the reflex inhibition in the electromyographic activity of scalene muscles in response to inspiratory muscle loading is present in individuals with cervical spinal cord injury and to examine whether the intercostal muscle afferents are critical for genesis of the reflex.

What is the main finding and its importance?

The lack of reflex inhibition in response to inspiratory loading in individuals with complete cervical spinal cord injury suggests that the reflex critically requires input from intercostal afferents and/or an intact intersegmental neural network.

In healthy individuals, transient loading of inspiratory muscles with a brief inspiratory occlusion produces a short‐latency inhibitory response (IR) in the electromyographic activity of scalene muscles at ∼40 ms, followed by an excitatory response (ER). It has been argued that this reflex plays a protective role in neuromuscular control of the inspiratory muscles and that it is co‐ordinated by spinal segmental or supraspinal circuits. In this study, the reflex response to airway occlusion was recorded bilaterally from scalene muscles in 14 subjects and from the right costal diaphragm in seven subjects with spinal cord injury [SCI, C4–C6; American Spinal Injury Association (ASIA) Impairment Scale (AIS) A]. The incidence, latency and size of the reflex were compared with previously published data from able‐bodied subjects. Only two subjects with SCI showed an IR, and six subjects had an ER. Latencies to the onset and peak of the IR and ER were 5–50 ms longer than in able‐bodied subjects. However, when reflexes were identified, their size in individuals with SCI was similar to that of control subjects. We conclude that afferents from the scalene muscles and diaphragm are insufficient in most subjects with SCI to evoke the usual inhibition to airway occlusion and that input from chest wall afferents below the spinal cord lesion may be important for genesis of the short‐latency inhibition in the able‐bodied subjects.
The role of gastrointestinal vagal afferent fibres in obesity
Authors: Kentish Stephen J. , Page Amanda J.
Published: November 2014

Gastrointestinal (GI) vagal afferents are a key mediatory of food intake. Through a balance of responses to chemical and mechanical stimuli food intake can be tightly controlled via the ascending satiety signals initiated in the GI tract. However, vagal responses to both mechanical and chemical stimuli are modified in diet‐induced obesity (DIO). Much of the research to date whilst in relatively isolated/controlled circumstances indicates a shift between a balance of orexigenic and anorexigenic vagal signals to blunted anorexigenic and potentiated orexigenic capacity. Although the mechanism responsible for the DIO shift in GI vagal afferent signalling is unknown, one possible contributing factor is the gut microbiota. Nevertheless, whatever the mechanism, the observed changes in gastrointestinal vagal afferent signalling may underlie the pathophysiological changes in food consumption that are pivotal for the development and maintenance of obesity.

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Molecular mechanisms of temperature adaptation
Authors: Bagriantsev Sviatoslav N. , Gracheva Elena O.
Published: November 2014

Thermal perception is a fundamental physiological process pertaining to the vast majority of organisms. In vertebrates, environmental temperature is detected by the primary afferents of the somatosensory neurons in the skin, which express a ‘choir’ of ion channels tuned to detect particular temperatures. Nearly two decades of research have revealed a number of receptor ion channels that mediate the perception of several temperature ranges, but most still remain molecularly orphaned. Yet even within this well‐researched realm, most of our knowledge largely pertains to two closely related species of rodents, mice and rats. While these are standard biomedical research models, mice and rats provide a limited perspective to elucidate the general principles that drive somatosensory evolution. In recent years, significant advances have been made in understanding the molecular mechanism of temperature adaptation in evolutionarily distant vertebrates and in organisms with acute thermal sensitivity. These studies have revealed the remarkable versatility of the somatosensory system and highlighted adaptations at the molecular level, which often include changes in biophysical properties of ion channels from the transient receptor potential family. Exploiting non‐standard animal models has the potential to provide unexpected insights into general principles of thermosensation and thermoregulation, unachievable using the rodent model alone.
Short‐chain fatty acid sensing in rat duodenum
Authors: Akiba Yasutada , Inoue Takuya , Kaji Izumi , Higashiyama Masaaki , Narimatsu Kazuyuki , Iwamoto Ken‐ichi , Watanabe Masahiko , Guth Paul H. , Engel Eli , Kuwahara Atsukazu , Kaunitz Jonathan D
Published: November 2014

Key points

Luminal lipid in the duodenum modulates gastroduodenal functions via the release of gut hormones and mediators such as cholecystokinin and 5‐HT.

The effects of luminal short‐chain fatty acids (SCFAs) in the foregut are unknown.

Free fatty acid receptors (FFARs) for long‐chain fatty acids (LCFAs) and SCFAs are expressed in enteroendocrine cells. SCFA receptors, termed FFA2 and FFA3, are expressed in duodenal enterochromaffin cells and L cells, respectively.

Activation of LCFA receptor (FFA1) and presumed FFA3 stimulates duodenal HCO3− secretion via a glucagon‐like peptide (GLP)‐2 pathway, whereas FFA2 activation induces HCO3− secretion via muscarinic and 5‐HT4 receptor activation.

The presence of SCFA sensing in the duodenum with GLP‐2 and 5‐HT signals further supports the hypothesis that luminal SCFA in the foregut may contribute towards the generation of functional symptoms.

Intraduodenal fatty acids (FA) and bacterial overgrowth, which generate short‐chain FAs (SCFAs), have been implicated in the generation of functional dyspepsia symptoms. We studied the mechanisms by which luminal SCFA perfusion affects duodenal HCO3− secretion (DBS), a measure of mucosal neurohumoral activation. Free fatty acid receptor (FFAR) 1 (FFA1), which binds long‐chain FA (LCFA), and SCFA receptors FFA2 and FFA3 were immunolocalised to duodenal enteroendocrine cells. FFA3 colocalised with glucagon‐like peptide (GLP)‐1, whereas FFA2 colocalised with 5‐HT. Luminal perfusion of the SCFA acetate or propionate increased DBS, enhanced by dipeptidyl peptidase‐IV (DPPIV) inhibition, at the same time as increasing GLP‐2 portal blood concentrations. Acetate‐induced DBS was partially inhibited by monocarboxylate/HCO3− exchanger inhibition without affecting GLP‐2 release, implicating acetate absorption in the partial mediation of DBS. A selective FFA2 agonist dose‐dependently increased DBS, unaffected by DPPIV inhibition or by cholecystokinin or 5‐HT3 receptor antagonists, but was inhibited by atropine and a 5‐HT4 antagonist. By contrast, a selective FFA1 agonist increased DBS accompanied by GLP‐2 release, enhanced by DPPIV inhibition and inhibited by a GLP‐2 receptor antagonist. Activation of FFA1 by LCFA and presumably FFA3 by SCFA increased DBS via GLP‐2 release, whereas FFA2 activation stimulated DBS via muscarinic and 5‐HT4 receptor activation. SCFA/HCO3− exchange also appears to be present in the duodenum. The presence of duodenal fatty acid sensing receptors that signal hormone release and possibly signal neural activation may be implicated in the pathogenesis of functional dyspepsia.
Silicon central pattern generators for cardiac diseases
Authors: Nogaret Alain , O'Callaghan Erin L. , Lataro Renata M. , Salgado Helio C. , Meliza C. Daniel , Duncan Edward , Abarbanel Henry D. I. , Paton Julian F. R.
Published: November 2014

Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronisation but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat‐to‐beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPGs) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPGs). We discuss the limitations of present CPGs and appraise the advantages of analog over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio‐respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin–Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease.