bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses
Authors: Retzepi M. , Calciolari E. , Wall I. , Lewis M. P. , Donos N.
Published: July 2017

Objectives

To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR).

Material and methods

Ninety‐three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5‐mm defect was created at the mid‐portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis.

Results

Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38–42%) and newly formed bone (54–61%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified.

Conclusions

Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population.
China's Housing Market Imbalance from 2003 to 2016: An Analysis Based on the User Cost Approach
Authors: Lai Pingyao
Published: July 2017

During 2003–2016, China experienced an unprecedented housing market imbalance. The present paper applies the user cost approach to conduct a systematic analysis of this important phenomenon, examines the policy factors behind the persistent housing market imbalance, and explores policy options to correct the housing market imbalance. We found that during most of 2003–2016, the user cost was significantly lower than 2 percent, caused by high income growth, rapid credit expansion and low interest rates, which led to the persistent housing market imbalance. Therefore, the government should control bank credit and introduce property taxes during the possession of houses.
What are the Determinants of Large‐scale Farming in China?
Authors: Xia Xing , Xin Xian , Ma Ling
Published: July 2017

The Chinese Government has increased its focus on expanding farm scale to promote agricultural development since 2010. A series of favorable polices has been adopted to support large‐scale farming. Using a multivariate probit model and 2015 and 2016 rural household survey data, the present paper examines the factors that influence small farmers' decision to become large‐scale farmers. The empirical regression results suggest that the decision to become a large‐scale farmer is significantly influenced by household human capital, cooperative membership, marketing channels, land‐transfer contracts and government policies. However, the influence of these factors differs with respect to becoming large‐scale grain and non‐grain farmers. These results imply that policy tools should target these factors and the appropriate group of small‐scale farmers. Generally, both central and local governments should promote large‐scale farming by enhancing rural households' human capital, improving marketing channels and providing agricultural social services, as well as encouraging returning migrant workers to engage in large‐scale farming.
Molecular markers reveal reproductive strategies of non‐pollinating fig wasps
Authors: COOK JAMES M. , REUTER CAROLINE , MOORE JAMIE C. , WEST STUART A.
Published: July 2017

1. Fig wasps have proved extremely useful study organisms for testing how reproductive decisions evolve in response to population structure. In particular, they provide textbook examples of how natural selection can favour female‐biased offspring sex ratios, lethal combat for mates and dimorphic mating strategies.

2. However, previous work has been challenged, because supposedly single species have been discovered to be a number of cryptic species. Consequently, new studies are required to determine population structure and reproductive decisions of individuals unambiguously assigned to species.

3. Microsatellites were used to determine species identity and reproductive patterns in three non‐pollinating Sycoscapter species associated with the same fig species. Foundress number was typically one to five and most figs contained more than one Sycoscapter species. Foundresses produced very small clutches of about one to four offspring, but one foundress may lay eggs in several figs.

4. Overall, the data were a poor match to theoretical predictions of solitary male clutches and gregarious clutches with n − 1 females. However, sex ratios were male‐biased in solitary clutches and female‐biased in gregarious ones.

5. At the brood level (all wasps in a fig), a decrease in sex ratio with increasing brood size was only significant in one species, and sex ratio was unrelated to foundress number. In addition, figs with more foundresses contain more wasp offspring.

6. Finally, 10–22% of females developed in patches without males. As males are wingless, these females disperse unmated and are constrained to produce only sons from unfertilised eggs.
Bioavailability and tolerability of nebulised dexamethasone sodium phosphate in adult horses
Authors: Haspel A. D. , Giguère S. , Hart K. A. , Berghaus L. J. , Davis J. L.
Published: July 2017

Background

Nebulisation of the injectable dexamethasone sodium phosphate (DSP) would offer an inexpensive way of delivering a potent corticosteroid directly to the lungs of horses with asthma. However, this approach would be advantageous only if systemic absorption is minimal and if the preservatives present in the formulation do not induce airway inflammation.

Objective

To investigate the bioavailability of nebulisedDSPand determine whether it induces airway inflammation or hypothalamic‐pituitary‐adrenal (HPA) axis suppression in healthy adult horses.

Study design

Randomised crossover experiment.

Methods

Dexamethasone sodium phosphate was administered to six healthy adult horses at a dose of 5 mg q. 24 h for 5 days via nebulised, or intravenous (i.v.) routes. Plasma dexamethasone concentrations were measured byUPLC/MS‐MSto calculate bioavailability. Cytological examination of bronchoalveolar fluid was performed at baseline and after the last dose ofDSP. A validated chemiluminescent immunoassay was used to measure basal serum cortisol concentrations.

Results

After nebulisation to adult horses, dexamethasone had a mean (±s.d.) maximum plasma concentration of 0.774 ± 0.215 ng/mL and systemic bioavailability of 4.3 ± 1.2%. Regardless of route of administration, there was a significant decrease in the percentage of neutrophils in bronchoalveolar lavage fluid over time. During i.v. administration, basal serum cortisol concentration decreased significantly from baseline to Day 3 and remained low on Day 5. In contrast, basal serum cortisol concentration did not change significantly during administration via nebulisation.

Main limitations

Small sample size and short period of drug administration.

Conclusions

Dexamethasone sodium phosphate administered via nebulisation had minimal systemic bioavailability and did not induce lower airway inflammation orHPAaxis suppression in healthy horses.
Effect of PNPLA3 I148M polymorphism on histologically proven non‐alcoholic fatty liver disease in liver transplant recipients
Authors: Kim Hyeyoung , Lee Kwang‐Woong , Lee Kyoungbun , Seo Sooin , Park Min‐Young , Ahn Sung Woo , Hong Suk Kyun , Yoon Kyung Chul , Kim Hyo‐Sin , Choi YoungRok , Lee Hae Won , Yi Nam‐Joon , Suh Kyung‐Suk
Published: July 2017

Aim

PNPLA3 I148M polymorphism (rs738409 C>G) is the most important and best‐known polymorphism for non‐alcoholic fatty liver disease (NAFLD). However, little is known about the effect of this polymorphism on NAFLD after liver transplantation (LT). We aimed to evaluate the association between this polymorphism and post‐LT NAFLD.

Methods

We designed a prospective case–control study. Among adult recipients who underwent LT between April 2014 and October 2015, those whose whole blood was preoperatively collected for genotyping in both recipients and coupled donors and those who underwent protocol biopsy at 1 year post‐LT were enrolled.

Results

A total of 32 recipients were enrolled. Histologically proven steatosis (≥5%) was present in 28.1% of patients at a mean time of 12.7 ± 2.0 months after LT. Moderate and more severe steatosis (≥33%) was present in 9.4%. One year after LT, steatosis was present in 50.0% of homozygous recipients with the rs738409‐G allele. It was present in 27.3% of heterozygous recipients with the rs738409‐G allele, and in 9.1% (P = 0.041) of recipients with rs738409‐CC. The genotype of the donor was not significantly (P = 0.647) associated with post‐LT NAFLD. When both recipient and coupled donor showed heterogeneous or homozygous genotype of the rs738409‐G allele, there was significantly more post‐LT NAFLD compared to that in others (47.1% vs. 6.7%; P = 0.018). In univariate and multivariate analyses, only the presence of the rs738409‐G risk allele in both donor and recipient was a significant risk factor for post‐LT NALFD (relative risk, 26.95; P = 0.048).

Conclusions

PNPLA3 I148M polymorphism can significantly affect histologically proven NAFLD at 1 year post‐LT.
The impact of immunoglobulin in acute HIV infection on the HIV reservoir: a randomized controlled trial
Authors: Tiraboschi J , Ray S , Patel K , Teague A , Pace M , Phalora P , Robinson N , Hopkins E , Meyerowitz J , Wang Y , Cason J , Kaye S , Sanderson J , Klenerman P , Fidler S , Frater J , Fox J
Published: July 2017

Objectives

Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV‐specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone.

Methods

Ten men with AHI (Fiebig II−IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV‐1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19). Blood samples were evaluated for viral reservoir, immune activation, immune exhaustion and microbial translocation. Flexible sigmoidoscopy was performed at weeks 19, 24 and 48, and gut proviral DNA and cell numbers determined.

Results

IVIG was well tolerated and no viral blips (> 50 HIV‐1 RNA copies/mL) occurred during IVIG therapy. From baseline to week 48, total HIV DNA in peripheral blood mononuclear cells (PBMCs) (cases: −3.7 log10 copies/106 CD4 cells; controls: −3.87 log10 copies/106 CD4 cells) declined with no differences observed between the groups (P = 0.49). Declines were observed in both groups from week 19 to week 48 in total HIV DNA in PBMCs (P = 0.38), serum low copy RNA (P = 0.57) and gut total HIV DNA (P = 0.55), but again there were no significant differences between arms. Biomarkers of immune activation, immune exhaustion and microbial translocation and the CD4:CD8 ratio were similar between arms for all comparisons.

Conclusions

Although safe, IVIG in AHI did not impact total HIV DNA, immune function or microbial translocation in peripheral blood or gut tissue.
Disconnected lives: Women with intellectual disabilities in conflict with the law
Authors: Levine Kathryn Ann , Proulx Jocelyn , Schwartz Karen
Published: July 2017

Background

Women with intellectual/developmental disabilities in conflict with the law experience childhood trauma, substance abuse and intimate partner violence but continue to have difficulty accessing appropriate therapeutic services, both within correctional settings and upon discharge. The aim of this study is to explore women's service needs and to critically assess whether the available services are meeting their identified needs.

Method

Semi‐structured interviews were conducted with 16 women with intellectual/developmental disabilities who were in the Special Needs Unit of a women's correctional centre from December 2014 to March 2015.

Results

Women with intellectual/developmental disabilities struggle to manage the impact of intergenerational trauma, exacerbated by issues of substance abuse and addiction, poor coping skills and minimal education, all of which impact their sense of well‐being.

Conclusions

This study highlights the need for increasing trauma treatment for women with intellectual/developmental disabilities, and emphasizes the need for accessible intervention to facilitate coping, trauma processing and community integration.
Development and implementation of a clinical pathway for cardiac surgery in the intensive care unit: Effects on protocol adherence
Authors: van der Kolk Marion , van den Boogaard Mark , ter Brugge‐Speelman Corine , Hol Jeroen , Noyez Luc , van Laarhoven Kees , van der Hoeven Hans , Pickkers Peter
Published: July 2017

Rationale, aims and objectives

Cardiac surgery (CS) is facilitated by multiple perioperative guidelines and protocols. Use of a clinical pathway (CP) may facilitate the care of these patients.

Methods

This is a pre‐post design study in the ICU of a tertiary referral centre. A CP for CS patients in the ICU was developed by ICU‐nurses and enabled them to execute proactively predefined actions in accordance with and within the preset boundaries which were part of a variance report. A tailored implementation strategy was used. Primary outcome measure was protocol adherence above 80% on the domains of blood pressure control, action on chest tube blood loss and electrolyte control within the CP.

Results

In a 4‐month period, 84 consecutive CP patients were included and compared with 162 matched control patients admitted in the year before implementation; 3 patients were excluded. Propensity score was used as matching parameter. CP patients were more likely to receive early adequate treatment for derangements in electrolytes (96% vs 47%, P < .001), blood pressure (90% vs 49%, P < .001) and adequate treatment for chest tube blood loss (90% vs 10%, P < .001). We found no differences in hospital and ICU LOS, ICU readmission or mortality.

Conclusion

Use of the CP improved postoperative ICU treatment for cardiac surgical patients. Implementation of a CP and the use of a special variance report could be a blueprint for the implementation and use of a CP in low‐volume high complex surgery.
Commitment, Forgiveness, and Relationship Self‐Regulation: An Actor Partner Interdependence Model of Relationship Virtues and Relationship Effort in Couple Relationships
Authors: Novak Joshua R. , Smith Heather M. , Larson Jeffry H. , Crane D. Russell
Published: July 2017

Dyadic data from 679 committed couples were used to examine associations between commitment, forgiveness, and perceptions of partner's relationship self‐regulation (RSR) behaviors—that is effort and strategies that partners exert to maintain the relationship. We found that for both partners, higher self‐reports of commitment and forgiveness were associated with higher perceptions of their partner's RSR. For females, higher commitment and forgiveness were associated with higher male perceptions of her RSR, and higher male forgiveness was associated with higher female perceptions of his RSR. These findings demonstrate the importance of marital virtues and relationship work and give credence to the marital competence model of “other‐centeredness” by Carroll et al. (2006, Journal of Family Issues, 27(7), 1001). Clinical implications are discussed.
Melatonin impedes Tet1‐dependent mGluR5 promoter demethylation to relieve pain
Authors: Hsieh Ming‐Chun , Ho Yu‐Cheng , Lai Cheng‐Yuan , Chou Dylan , Wang Hsueh‐Hsiao , Chen Gin‐Den , Lin Tzer‐Bin , Peng Hsien‐Yu
Published: July 2017

Melatonin (N‐acetyl‐5‐methoxytryptamine)/MT2 receptor‐dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten‐eleven translocation methylcytosine dioxygenase 1 (Tet1)‐dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2‐dependent analgesia involves spinal Tet1‐dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1‐encoding vectors to naïve rats produced profound and long‐lasting nociceptive hypersensitivity. In addition, enhanced Tet1 expression, Tet1‐metabotropic glutamate receptor subtype 5 (mGluR5) promoter coupling, demethylation at the mGluR5 promoter, and mGluR5 expression in dorsal horn neurons were observed. Rats subjected to spinal nerve ligation and intraplantar complete Freund's adjuvant injection displayed tactile allodynia and behavioral hyperalgesia associated with similar changes in the dorsal horn. Notably, intrathecal melatonin injection reversed the protein expression, protein‐promoter coupling, promoter demethylation, and pain hypersensitivity induced by Tet1 gene transfer, spinal nerve ligation, and intraplantar complete Freund's adjuvant injection. All the effects caused by melatonin were blocked by pretreatment with a MT2 receptor‐selective antagonist. In conclusion, melatonin relieves pain by impeding Tet1‐dependent demethylation of mGluR5 in dorsal horn neurons through the MT2 receptor. Our findings link melatonin/MT2 signaling to Tet1‐dependent epigenetic demethylation of nociceptive genes for the first time and suggest melatonin as a promising therapy for the treatment of pain.
Brainstem auditory evoked responses in 37 dogs with otitis media before and after topical therapy
Authors: Paterson S.
Published: July 2017

Objectives

The objective of this study was to determine whether intra‐aural administration of aqueous solutions of marbofloxacin, gentamicin, tobramycin and ticarcillin (used off‐licence) was associated with changes in hearing as measured by brainstem auditory evoked responses.

Materials and Methods

Dogs diagnosed with otitis media (n=37) underwent brainstem auditory evoked response testing and then were treated for their ear disease. First, the external ear canal and middle ear were flushed with sterile saline followed by EDTA tris with 0·15% chlorhexidine. Then, a combination of aqueous antibiotic mixed with an aqueous solution of EDTA tris was instilled into the middle ear. Follow‐up examinations were undertaken for each dog, and treatment was continued until there were no detected infectious organisms or inflammatory infiltrate. Brainstem auditory evoked response testing was repeated after resolution of the infection and discontinuation of therapy.

Results

Brainstem auditory evoked responses in dogs treated with aqueous solutions of marbofloxacin or gentamicin remained unchanged or improved after therapy of otitis media but were impaired in dogs treated with ticarcillin or tobramycin.

Clinical Significance

If off‐licence use of topical antibiotics is deemed necessary in cases of otitis media, aqueous solutions of marbofloxacin and gentamicin appear to be less ototoxic than aqueous solutions of ticarcillin or tobramycin.
Creativity in local government: Definition and determinants
Authors: Kruyen Peter M. , van Genugten Marieke
Published: July 2017

In current thinking about public service improvement, civil servant creativity plays an important role. Using the results of 43 semi‐structured interviews, we assessed the degree to which our theoretical knowledge about creativity—based primarily on business research—matches the insights of managers in local government. Respondents considered employee creativity to be important, but—in contrast to the literature—understood creativity as the act of trying out new things to better deal with specific problems at hand instead of developing new ideas potentially applicable to a wider context. As such, respondents did not see creativity as the main precondition for innovation. In line with the literature, there is little consistency across respondents about individual‐ and context‐level determinants of creativity. Lastly, respondents put forward several factors that have received little attention in the literature but are particularly relevant in understanding differences in work‐related creativity in the context of local government.
Multidimensional assessment of quality of life of children and problems of parents in Indian society after pediatric renal transplant: Beyond the conventional thoughts
Authors: Yadav Priyank , Nunia Sandeep , Bansal Ankur , Sureka Sanjoy K. , Jena Rahul , Ansari Mohd. Sualeh , Srivastava Aneesh
Published: July 2017

This study evaluated multidimensional QoL after renal transplant to find the physical, psychosocial, and economic issues after pediatric transplant. Sixty‐two patients under the age of 18 at the time of assessment were asked to complete WHOQOL questionnaires. Assessment of behavioral, emotional status of child, problems of parents, and SEC of family were also performed. The beneficial effect of transplantation was observed across all domains of QoL (physical, psychological, social, environmental, and overall QoL). The greatest change was observed in QoL domains that dealt with overall satisfaction (81.28±15.76 vs 45.32±10.98; P<.0001). The domain dealing with environmental factors showed the least variation after transplantation (65.58±17.45 vs 51.34±17.81; P<.0001). Feelings of happiness and peer group socialization were reported in 81% and 69% of patients, respectively. There was no marital disharmony in 52% of families. However, SEC deteriorated in 16% of families and 59% of the families availed financial assistance. Sixty‐nine percent of children had not attended school after one year of transplantation, but return to school after transplant was reduced to 8% at 5 years. Pre‐ and post‐transplant social and psychological support may help these patients and their families adjust in society and have a positive outlook for their future.
A systematic review of the prevalence and impact of urinary incontinence in cystic fibrosis
Authors: Frayman Katherine B. , Kazmerski Traci M. , Sawyer Susan M.
Published: July 2017

This systematic review synthesizes published articles investigating the prevalence, severity and impact of urinary incontinence (UI), a condition associated with cystic fibrosis (CF). References were identified through searching Medline, Embase and PubMed using the medical subject headings ‘cystic fibrosis’ AND ‘urinary incontinence’. Articles were included if UI prevalence was investigated as an outcome. Twelve studies met selection criteria. The prevalence of UI ranged from 5% to 76%. Age and gender contributed to this variability. When assessed, UI commonly limited airway clearance, exercise and/or spirometry, and had a variable impact on patients’ lives. Worry and embarrassment were features for many; others were less affected. In CF, UI is common and can interfere with respiratory care and social well‐being. The prevalence, characteristics and impact are poorly understood, which is made worse by inconsistent definitions across studies. Future research is needed to improve approaches to prevention, identification, management and education.
Unification of some multivariate process capability indices for asymmetric specification region
Authors: Chatterjee Moutushi , Chakraborty Ashis Kumar
Published: July 2017

In manufacturing industries, it is often seen that the bilateral specification limits corresponding to a particular quality characteristic are not symmetric with respect to the stipulated target. A unified superstructureof univariate process capability indices was specially designed for processes with asymmetric specification limits. However, as in most of the practical situations a process consists of a number of inter‐related quality characteristics, subsequently, a multivariate analogue of, which is calledCM(u,v), was developed. In the present paper, we study some properties ofCM(u,v) like threshold value and compatibility with the asymmetry in loss function. We also discuss estimation procedures for plug‐in estimators of some of the member indices ofCM(u,v). Finally, the superstructure is applied to a numerical example to supplement the theory developed in this article.
Scope to map soil management units at the district level from remotely sensed γ‐ray spectrometry and proximal sensed EM induction data
Authors: Jing Y. Z. , Huang J. , Banks R. , Triantafilis J.
Published: July 2017

The traditional method of soil mapping involves classifying soil into pre‐existing classes using morphological observations and then air‐photograph interpretation to extrapolate the information. To accelerate the process, less costly ancillary data can be used to assist mapping. However, digital soil mapping (DSM) is still affected by the classifications used to identify soil types. One reason is because the morphological characteristics are not mutually exclusive, which causes misclassification. In this study, we used a DSM approach, where ancillary data were surrogate for morphological data, with soil types identified by numerical clustering of remotely and proximally sensed data collected across a farming district near Gunnedah, Australia. Remotely sensed data were obtained from an air‐borne gamma‐ray (γ‐ray) spectrometer survey, including potassium (K), thorium (Th), uranium (U) and total counts. Proximally sensed data were measured using EM38 (i.e. EM38h and EM38v). Using fuzzy k‐means and a linear mixed model with measured physical (e.g. clay) and chemical (e.g. CEC) properties from the topsoil (0–0.30 m) and subsoil (0.9–1.2 m), we found that k = 5 was also optimal given that mean‐squared prediction error (i.e. ) was minimised. The approach highlighted subtle differences in physical and chemical properties in productive areas. The DSM was unsuccessful in identifying small units; however, inclusion of elevation data might overcome this limitation. This research has implications for providing fast, accurate and meaningful DSM at a district scale, where traditional methods are too expensive.
Can virtue be learned? An exploration of student learning experiences in ethics courses and their implications for influencing moral character
Authors: Agnew Cochran Elizabeth , Fozard Weaver Darlene
Published: July 2017

What does it mean to teach virtue, or to learn it? We consider this question through an institutional review board (IRB) supported research study attending to student learning experiences in undergraduate ethics courses at a Catholic university with an explicit commitment to social justice. This essay draws on and interprets qualitative data concerning the outcomes of select pedagogical approaches that involve exposing students to the experiences of others: the use of narratives; participation in structured experiential learning activities; and community engagement through deep listening and facilitated dialogue. We focus our interpretation around the implications of these pedagogies in relation to student understanding of and attitudes regarding three character traits identified as “other‐regarding” virtues in theological and philosophical scholarship – altruism, compassion, and solidarity. This paper considers the implications of these pedagogies and the practical effects of different sorts of teaching strategies on students' self‐understanding as moral agents.
Mainstreaming geography's decolonial imperative
Authors: Jazeel Tariq
Published: July 2017

This commentary makes three points in relation to the theme of ‘decolonising geographical knowledge’. First, it highlights the potential that the theme has in terms of widening the imperative to decolonise geographical knowledge; second, drawing on decolonial critiques of postcolonial theory, it stresses the structural difficulty of decolonisation efforts that are conceived within extant disciplinary infrastructures; and third, it argues that decolonising geographical knowledge should encourage geographers to, in fact, turn away from the discipline as we attempt to ‘speak to’ the places, peoples, and communities on and with which we work.
Aldehyde dehydrogenase 1 a1 regulates energy metabolism in adipocytes from different species
Authors: Yang Kefeng , Adin Christopher , Shen Qiwen , Lee Ly James , Yu Lianbo , Fadda Paolo , Samogyi Arpad , Ham Kathleen , Xu Lu , Gilor Chen , Ziouzenkova Ouliana
Published: July 2017

Background

Survival and longevity of xenotransplants depend on immune function and ability to integrate energy metabolism between cells from different species. However, mechanisms for interspecies cross talk in energy metabolism are not well understood. White adipose tissue stores energy and is capable of mobilization and dissipation of energy as heat (thermogenesis) by adipocytes expressing uncoupling protein 1 (Ucp1). Both pathways are under the control of vitamin A metabolizing enzymes. Deficient retinoic acid production in aldehyde dehydrogenase 1 A1 (Aldh1a1) knockout adipocytes (KO) inhibits adipogenesis and increases thermogenesis. Here we test the role Aldh1a1 in regulation of lipid metabolism in xenocultures.

Methods

Murine wide‐type (WT) and KO pre‐adipocytes were encapsulated into a poly‐L‐lysine polymer that allows exchange of humoral factors <32kD via nanopores. Encapsulated murine adipocytes were co‐incubated with primary differentiated canine adipocytes. Then, expression of adipogenic and thermogenic genes in differentiated canine adipocytes was detected by real‐time polymerase chain reaction (PCR). The regulatory factors in WT and KO cells were identified by comparison of secretome using proteomics and in transcriptome by gene microarray.

Results

Co‐culture of encapsulated mouse KO vs WT adipocytes increased expression of peroxisome proliferator‐activated receptor gamma (Pparg), but reduced expression of its target genes fatty acid binding protein 4 (Fabp4), and adipose triglyceride lipase (Atgl) in canine adipocytes, suggesting inhibition of PPARγ activation. Co‐culture with KO adipocytes also induced expression of Ucp1 in canine adipocytes compared to expression in WT adipocytes. Cumulatively, murine KO compared to WT adipocytes decreased lipid accumulation in canine adipocytes. Comparative proteomics revealed significantly higher levels of vitamin A carriers, retinol binding protein 4 (RBP4), and lipokalin 2 (LCN2) in KO vs WT adipocytes.

Conclusions

Our data demonstrate the functional exchange of regulatory factors between adipocytes from different species for regulation of energy balance. RBP4 and LCN2 appear to be involved in the transport of retinoids for regulation of lipid accumulation and thermogenesis in xenocultures. While the rarity of thermogenic adipocytes in humans and dogs precludes their use for autologous transplantation, our study demonstrates that xenotransplantation of engineered cells could be a potential solution for the reduction in obesity in dogs and a strategy for translation to patients.
Gene expression analyses reveal metabolic specifications in acute O2‐sensing chemoreceptor cells
Authors: Gao Lin , Bonilla‐Henao Victoria , García‐Flores Paula , Arias‐Mayenco Ignacio , Ortega‐Sáenz Patricia , López‐Barneo José
Published: July 2017

Key points

Glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM) are essential for reflex cardiorespiratory adaptation to hypoxia. However, the mechanisms whereby these cells detect changes in O2 tension are poorly understood.

The metabolic properties of acute O2‐sensing cells have been investigated by comparing the transcriptomes of CB and AM cells, which are O2‐sensitive, with superior cervical ganglion neurons, which are practically O2‐insensitive.

In O2‐sensitive cells, we found a characteristic prolyl hydroxylase 3 down‐regulation and hypoxia inducible factor 2α up‐regulation, as well as overexpression of genes coding for three atypical mitochondrial electron transport subunits and pyruvate carboxylase, an enzyme that replenishes tricarboxylic acid cycle intermediates.

In agreement with this observation, the inhibition of succinate dehydrogenase impairs CB acute O2 sensing. The responsiveness of peripheral chemoreceptor cells to acute hypoxia depends on a ‘signature metabolic profile’.

Acute O2 sensing is a fundamental property of cells in the peripheral chemoreceptors, e.g. glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM), and is necessary for adaptation to hypoxia. These cells contain O2‐sensitive ion channels, which mediate membrane depolarization and transmitter release upon exposure to hypoxia. However, the mechanisms underlying the detection of changes in O2 tension by cells are still poorly understood. Recently, we suggested that CB glomus cells have specific metabolic features that favour the accumulation of reduced quinone and the production of mitochondrial NADH and reactive oxygen species during hypoxia. These signals alter membrane ion channel activity. To investigate the metabolic profile characteristic of acute O2‐sensing cells, we used adult mice to compare the transcriptomes of three cell types derived from common sympathoadrenal progenitors, but exhibiting variable responsiveness to acute hypoxia: CB and AM cells, which are O2‐sensitive (glomus cells > chromaffin cells), and superior cervical ganglion neurons, which are practically O2‐insensitive. In the O2‐sensitive cells, we found a characteristic mRNA expression pattern of prolyl hydroxylase 3/hypoxia inducible factor 2α and up‐regulation of several genes, in particular three atypical mitochondrial electron transport subunits and some ion channels. In addition, we found that pyruvate carboxylase, an enzyme fundamental to tricarboxylic acid cycle anaplerosis, is overexpressed in CB glomus cells. We also observed that the inhibition of succinate dehydrogenase impairs CB acute O2 sensing. Our data suggest that responsiveness to acute hypoxia depends on a ‘signature metabolic profile’ in chemoreceptor cells.
PI3Kγ activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity
Authors: Breasson Ludovic , Becattini Barbara , Sardi Claudia , Molinaro Angela , Zani Fabio , Marone Romina , Botindari Fabrizio , Bousquenaud Mélanie , Ruegg Curzio , Wymann Matthias P. , Solinas Giovanni
Published: July 2017

The kinase PI3Kγ aggravates obesity by activating macrophages and triggering inflammation in adipose tissue.
Impact of a Carbapenem Antimicrobial Stewardship Program on Patient Outcomes
Authors: Seah Valerie Xue Fen , Ong Rina Yue Ling , Lim Ashley Shi Yuan , Chong Chia Yin , Tan Natalie Woon Hui , Thoon Koh Cheng
Published: July 2017

Antimicrobial stewardship programs (ASPs) aim to improve appropriate antimicrobial use. However, concerns of the negative consequences from accepting ASP interventions exist, particularly when deescalation or discontinuation of broad-spectrum antibiotics is recommended. Hence, we sought to evaluate the impact on clinical outcomes when ASP interventions for inappropriate carbapenem use were accepted or rejected by primary providers. We retrospectively reviewed all carbapenem prescriptions deemed inappropriate according to institutional guidelines with ASP interventions between July 2011 and December 2014. Intervention acceptance and outcomes, including carbapenem utilization, length of stay, hospitalization charges, 30-day readmission, and mortality rates were reviewed. Data were analyzed in two groups, one in which physicians accepted all interventions (“accepted”) and one in which interventions were rejected (“rejected”). A total of 158 ASP interventions were made. These included carbapenem discontinuation (35%), change to narrower-spectrum antibiotic (32%), dose optimization (17%), further investigations (including imaging and procalcitonin) (11%), infectious diseases referral (3%), antibiotic discontinuation (other than carbapenem) (1%), and source control (1%). Of 220 unique patients, carbapenem use was inappropriate in 101 (45.9%) patients. A significant reduction in carbapenem utilization was observed in the accepted group versus rejected group (median defined daily doses, 0.224 versus 0.668 per 1,000 patient-days, respectively;P< 0.001). There was a significant reduction in 30-day mortality in the accepted (none) versus rejected group (10 deaths,P= 0.015), but there were no differences in length of stay, hospitalization charge, or 30-day readmission rates. Hypotension was independently associated with mortality in multivariate analysis (odds ratio, 5.25; 95% confidence interval, 1.34 to 20.6). In our institution, acceptance of carbapenem ASP interventions did not compromise patient safety in terms of clinical outcomes while reducing consumption.
Intestinal Epithelial Ecto-5′-Nucleotidase (CD73) Regulates Intestinal Colonization and Infection by Nontyphoidal Salmonella
Authors: Kao Daniel J. , Saeedi Bejan J. , Kitzenberg David , Burney Krista M. , Dobrinskikh Evgenia , Battista Kayla D. , Vázquez-Torres Andrés , Colgan Sean P. , Kominsky Douglas J.
Published: July 2017

Ecto-5′-nucleotidase (CD73) is expressed abundantly on the apical surface of intestinal epithelial cells (IECs) and functions as the terminal enzyme in the generation of extracellular adenosine. Previous work demonstrated that adenosine signaling in IECs results in a number of tissue-protective effects during inflammation; however, a rationale for its apical expression has been lacking. We hypothesized that the highly polarized expression of CD73 is indicative of an important role for extracellular adenosine as a mediator of host-microbe interactions. We show that adenosine harbors bacteriostatic activity against
Salmonella enterica
serovar Typhimurium that is not shared by the related purine metabolite 5′-AMP, inosine, or hypoxanthine. Analysis of
Salmonella
colonization in IEC-specific CD73 knockout mice (
CD73

f/f

Villin

Cre

) revealed a nearly 10-fold increase in colonization compared to that in controls. Despite the increased luminal colonization by
Salmonella
,
CD73

f/f

Villin

Cre

mice were protected against
Salmonella
colitis and showed reduced
Salmonella
burdens in viscera, suggesting that adenosine promotes dissemination. The knockdown of CD73 expression in cultured IECs resulted in dramatic defects in intraepithelial localization and replication as well as defective transepithelial translocation by
Salmonella
. In conclusion, we define a novel antimicrobial activity of adenosine in the gastrointestinal tract and unveil an important role for adenosine as a regulator of host-microbe interactions. These findings have broad implications for the development of new therapeutic agents for infectious disease.
Disseminated cryptococcosis in an immunocompetent patient
Authors: Mada Pradeep , Nowack Brad , Cady Beth , Joel Chandranesan Andrew Stevenson
Published: July 2017

Cryptococcosis is a fungal infection which is commonly associated with immune-compromised state. Disseminated infection in immunocompetent individuals is extremely rare. We present a case of a 56-year-old African American patient who presented with unilateral knee pain and swelling and was subsequently diagnosed with cryptococcal bone mass with dissemination of infection.
Hyperacute muscle weakness in an unusual coexistence of antisignal recognition particle and anti-Mi-2 antibodies
Authors: Akintayo Richard Oluyinka , Agbola Olanrewaju Festus , Adeyemo Abiodun Waliyullah , Adelowo Olufemi
Published: July 2017

Idiopathic inflammatory myopathies are a heterogeneous group of systemic diseases characterised by variable phenotypes of chronic progressive muscle weakness. Myositis-specific antibodies (MSAs) include antibodies to cytoplasmic signal recognition particle (SRP) and various tRNA synthetases as well as the nuclear helicase protein Mi-2. These antibodies are typically found only in a fraction of true myositis cases and they tend to be mutually exclusive. Few cases of coexistence of two MSAs in the same patient have been reported and these cases all involve an antisynthetase antibody coexisting with either anti-SRP or anti-Mi-2 antibody. Peculiar clinical manifestations may be associated with different combinations of MSAs but the rarity of these cases makes their characterisation difficult. We report the first ever case of anti-SRP and anti-Mi-2 copositive polymyositis in a 19-year-old boy who presented with a week history of profound muscle weakness that attained its peak within 24â€‰hours of onset.
Is the mechanism of re-expansion pulmonary oedema in a heart–lung interaction?
Authors: Mokotedi Candy Masego , Balik Martin
Published: July 2017

The mechanism of re-expansion pulmonary oedema (Re-PE) is unclear. There are multiple variables in play when evaluating the response to evacuation of pleural fluid. We present an educational case of a critically ill patient admitted for respiratory failure who was fully dependent on ventricular pacing set at a constant rate throughout the episode of Re-PE. The transthoracic echocardiography (TTE) showed an ejection fraction of 38%, moderate mitral regurgitation (MR), mildly dilated right ventricle and moderate pulmonary hypertension. A pleural tap evacuated 850 mL of transudate, which was followed by tachypnoea and deteriorating oxygenation. Another repeat TTE revealed a Re-PE with elevated left ventricular end-diastolic pressure, severe MR, increased pulmonary hypertension and a decrease in stroke volume. There were no parallel changes in ventilation modality, heart rate, fluid therapy and vasopressor dosage. The treatment was initiated with dobutamine. The patient was extubated the next day and was later discharged to the cardiology department.
Determining clinical decision thresholds for HIV-positive patients suspected of having tuberculosis
Authors: Boyles Tom , Locatelli Isabella , Senn Nicolas , Ebell Mark
Published: July 2017

Clinical decision thresholds may aid the evaluation of diagnostic tests but have rarely been determined for tuberculosis (TB). We presented clinicians with six web-based clinical scenarios, describing patients with HIV and possible TB at various sites and with a range of clinical stability. The probability of disease was varied randomly and clinicians asked to make treatment decisions; threshold curves and therapeutic thresholds were calculated. Test and treatment thresholds were calculated using Bayes theorem and the diagnostic accuracy of Xpert MTB/RIF. We received 165 replies to our survey. Therapeutic thresholds vary depending on the clinical stability and site of suspected disease. For inpatients, it ranges from 3.4% in unstable to 79.6% in stable patients. For TB meningitis, it ranges from 0% in unstable to 51.4% in stable patients and for pulmonary TB in outpatients it ranges from 29.1% in unstable to 74.5% in the stable patients. Test and treatment thresholds vary in a similar way with test thresholds ranging from 0 in unstable patients with suspected meningitis to 8.2% for stable inpatients. Treatment thresholds vary from 0 for unstable patients with suspected meningitis to 97% for stable inpatients. Therapeutic thresholds for TB can be determined by presenting clinicians with patient scenarios with random probabilities of disease and can be used to calculate test and treatment thresholds using Bayes theorem. Thresholds are lower when patients are more clinically unstable and when the implications of inappropriately withholding therapy are more serious. These results can be used to improve use and evaluation of diagnostic tests.
The Risk of Ischemic Events Increased in Patients with Asymptomatic Carotid Stenosis with Decreased Cerebrovascular Reserve
Authors: Liu Shulan , Cai Jing , Ge Fugui , Yue Wei
Published: July 2017

Identifying high-risk patients with asymptomatic carotid stenosis (ACS) is necessary regardless of whether intensive medical therapy or aggressive treatment is applied. In order to assess the relationship between cerebrovascular reserve (CVR) measured by perfusion CT with inhalation of CO2 and the risk of ischemic events in ACS, this long-term follow-up study was conducted. Forty-five patients with ACS who underwent the examination of CVR measured by perfusion CT with inhalation of CO2 were collected and followed-up for at least 5 years. The primary end point was the occurrence of ipsilateral cerebral ischemic events. HRs and their 95% CI were calculated by Kaplan-Meier survival analysis and Cox regression models. The mean follow-up time was 68.7±10.7 months (40.0–84.0 months). 13 (28.9%) ipsilateral ischemic events were observed. The annual risk of ipsilateral ischemic events was 4.8%. Kaplan-Meier survival analysis and univariate Cox regression analysis indicated that patients with less CVR experienced more ischemic events (p=0.006 and p=0.013, respectively), which was confirmed by multiple Cox regression analysis (p=0.012). CVR measured by perfusion CT may potentially be the factor which can predict the risk of ipsilateral ischemic events in patients with ACS. Multidisciplinary management is necessary for these high-risk patients.
Ab initio calculations on structural and electronic transport properties of six-atom GaN clusters
Authors: Song Jinfeng , Long Xiaojiang , Hao Yanjun , Zhu Jun , Guo Yundong
Published: July 2017

The structural and electronic transport properties of GaxNy ([Formula: see text]) clusters are investigated in the framework of density functional theory (DFT). To get their most stable structures, a strategy of particle swarm optimization (PSO) algorithm is adopted. It is found that the most stable cluster’s binding energy and HOMO–LUMO gap energy decrease with Ga atom’s number in cluster increasing. The electronic transport properties of the clusters connected with two Al(100) electrodes are obtained by a method of combining nonequilibrium Green’s function (NEGF) with DFT. Equilibrium conductance of all six-atom GaN cluster is low (less than 0.65 G0), and Ga2N4 has the highest one (0.635 G0). Significant negative differential resistance (NDR) phenomenon is observed in configurations with cluster Ga2N4, Ga3N3 and Ga5N1, and these three clusters have almost the same current value in voltage region from 0.8 V to 1.3 V.