bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Too Many Private Equity Funds Top Quartile?
Authors: Harris Robert , Jenkinson Tim , Stucke Rüdiger
Published: December 2012

Assessing investment performance for private equity is inherently difficult due in large part to the nature of illiquid assets. Compounding this problem, investors and researchers alike are bedeviled by the existing lack of comprehensive, high‐quality data. The current state of affairs obscures answers to basic practical questions, leads to lack of standardization, and creates confusion.

This paper examines measurements of “top quartile” performance, a status widely prized in the industry, especially in light of past research showing return persistence by funds raised by the same general partner. Using three popular data sources and applying metrics typically adopted in the industry, the authors demonstrate that even modest variations in methods can result in half of all funds being able to claim “top quartile” results. Sources of variation include methods of categorizing funds, definitions of vintage year, choice of the data source, specification of performance metrics, and treatment of geography and currencies.
What Happens During the Private Period?: Evidence from Public‐to‐Private Reverse LBOs
Authors: Datta Sudip , Gruskin Mark , Iskandar‐Datta Mai
Published: December 2012

This study provides new evidence on the restructuring activities undertaken by public‐to‐private reverse leveraged buyouts (RLBOs) while owned by private equity firms. The authors' comprehensive sample of public‐to‐private LBOs that return to public ownership through IPOs enables them to observe changes in profitability, valuation, financial structure, operating structure, and cost structure from the time the firms go private through (and after) their emergence through (re‐) IPOs.

With their exclusive focus on reverse LBOs involving public‐to‐private deals, the authors reach findings that contradict previous conclusions about RLBOs. At the time of the LBO, the target firms in reverse LBOs are more levered than their peers, pay higher dividends, and are more profitable than their peers. At the same time, however, they appear to have lower market valuations before the buyouts.

During the private period, the target firms of reverse LBOs achieve significant increases in employee productivity, asset restructuring, and improved gross margins, while operating with substantially higher levels of debt financing, lower levels of cash and working capital, and greater concentration of equity ownership. After the companies return to public ownership through IPOs, such companies continue to operate with higher leverage and ownership concentration than their publicly traded peers while producing further increases in profitability, resulting in substantial increases in both enterprise and equity valuation. The authors' analysis also shows that higher debt levels from the buyout play an important role in increased enterprise values. The evidence suggests that possible undervaluation as well as expected efficiency gains from restructuring actions are the primary motives for such reverse LBOs.
The Case for Secondary Buyouts as Exit Channel
Authors: Achleitner Ann‐Kristin , Bauer Oliver , Figge Christian , Lutz Eva
Published: December 2012

Do private equity firms have a clear pecking order when deciding on exit channels for their portfolio companies? Are secondary buyouts—that is, sales to other PE firms—always an exit of last resort? And are there company‐ or market‐related factors that have a clear and predictable influence on decisions to pursue secondary buyouts?

Using a proprietary dataset of over 1,100 leveraged buyouts that exited in North America or Europe between 1995 and 2008, the authors attempt to answer these questions by analyzing the returns associated with public, private, and secondary (or “financial”) exits. Based on their analysis of the realized returns, there is no clear pecking order of exit types. Secondary buyouts deliver rates of return that are the equal of those achieved through public exits.

In addition, the authors assess the relationship between the likelihood of choosing a financial exit and certain company‐related as well as market‐related factors. Portfolio companies with greater debt capacity are more likely to be sold in secondary buyouts. Furthermore, increases in both the liquidity of debt markets and the amount of undrawn capital commitments to the private equity industry increase the probability of exit through secondary buyouts.
Do Private Equity Funds Increase Firm Value? Evidence from Japanese Leveraged Buyouts
Authors: Yeh Tsung‐ming
Published: December 2012

The author summarizes the findings of his recent study of 62 buyouts of listed Japanese companies by both Japanese and “foreign” private equity funds that were transacted between 2000 and 2007. Roughly half of the author's sample of transactions were accomplished by means of takeover bids by PE funds, and such deals were transacted at prices that represented a premium (of roughly 12%) to current market values. Most of the other PE transactions were privately negotiated deals in which the purchase prices involved discounts (of about 15% on average) to current value. For both sets of deals, however, the announcements of such buyouts were associated, on average, with a significantly positive stock market reaction.

By the cutoff date of the study (May 2010), 30 of the 62 acquired firms had realized “exits.” Those companies (though not the others) experienced significant average improvements in operating performance; and the extent of such improvements were roughly consistent with the size of the positive market reaction to the buyout announcements. The test results suggest that the value increases can be attributed to the more efficient use of assets and reduction of operating costs. Meanwhile, there was no evidence suggesting that the acquired firms cut back on their research and development, capital investments, or employee wages and growth. What's more, examination of the operating performance of the 30 companies after their exits showed no deterioration in profitability or investment spending.
CDS and the Resolution of Financial Distress
Authors: Lubben Stephen J. , Narayanan Rajesh P.
Published: December 2012

The dramatic growth of Credit Default Swaps (CDS)—contracts that allow creditors to hedge their default exposure or take leveraged credit positions—threatens to complicate the resolution of financial distress in ways that existing reorganization methods and institutions have yet to adapt to. CDS contracts undermine a major premise that underlies current reorganization methods—namely, that the holder of legal rights has, and is motivated by, corresponding economic interests. Because hedging in the CDS markets immunizes creditors from the debtor's financial condition, they effectively separate their legal rights and economic interests.

In this article, the authors discuss the challenges this separation poses for the resolution of distress both in and out of bankruptcy, and consider ways in which “on‐ground” realities may be reconciled with the legal structure that underlies the resolution of distress. At a minimum, disclosure of CDS positions in times of financial distress—along the lines of the disclosures presently required of equity investors under the Williams Act—are an essential first step toward a solution.
Foodways and Resilience under Apocalyptic Conditions
Authors: Morell‐Hart Shanti
Published: December 2012

Food is an active component of social and political process in times of daily plenty and in times of extreme scarcity. Routinized modes of foodways are hard to dislodge, even when resources and broad lifeways are violently disrupted. Ethnographic, ethnohistoric, and archaeological examples attest to the improvisational ability of individuals and communities when faced with food shortage. Using illustrations from around the world, I explore how approaches to linguistic practice contribute to discussions of starvation management. I posit that cultural redefinitions of food and foodways help to negotiate extreme circumstances and may extend even into postcrisis periods.
Resonance Magnetoelectric Effect in NaNbO3–NiFe2O4 Composite
Authors: Han Yemei , Li Lingxia , Wang Zhi , Guo Dong , Zhang Mingming
Published: December 2012

Electric field‐induced magnetization characteristics are demonstrated in (100−x)NaNbO3–xNiFe2O4(x = 15, 25, 35, 45), synthesized by the solid‐state sintering method. The composites show well‐defined ferroelectric behaviors and magnetic characteristics. The CME effect characteristics with driving frequency in a range 10 k–15 kHz were investigated at room temperature. The CME couplings increase initially with increasing the driving frequencies and then decrease with the further increase in the frequency. Large CME coefficients are obtained at electromechanical resonance frequency of 12.8 kHz. These lead‐free multiferroic composites exhibiting electrostatically induced ME resonance provide great opportunities for electric field‐tunable microwave devices.
Exploring the Development of Existing Sex Education Programmes for People with Intellectual Disabilities: An Intervention Mapping Approach
Authors: Schaafsma Dilana , Stoffelen Joke M. T. , Kok Gerjo , Curfs Leopold M. G.
Published: December 2012

Background

People with intellectual disabilities face barriers that affect their sexual health. Sex education programmes have been developed by professionals working in the field of intellectual disabilities with the aim to overcome these barriers. The aim of this study was to explore the development of these programmes.

Methods

Sex education programmes geared to people with intellectual disabilities were examined in the context of the Intervention Mapping protocol. Data were obtained via interviews with the programme developers.

Results

All programmes lack specific programme outcomes, do not have a theoretical basis, did not involve members of relevant groups in the development process and lack systematic evaluation.

Conclusions

Based on our findings and the literature, we conclude that these programmes are unlikely to be effective. Future programmes should be developed using a more systematic and theory‐ and evidence‐based approach.
Ex vivo high‐definition optical coherence tomography of basal cell carcinoma compared to frozen‐section histology in micrographic surgery: a pilot study
Authors: Maier T. , Kulichová D. , Ruzicka T. , Kunte C. , Berking C.
Published: December 2012

Background  Micrographic surgery is an established, but time‐consuming operating procedure for facial basal cell carcinoma (BCC). A new high‐definition (HD) optical coherence tomography (OCT) with high lateral and axial resolution in a horizontal (en‐face) and vertical (slice) imaging mode allows a fast and non‐invasive in vivo examination of BCC.

Objectives  To compare the diagnosis of BCC in excised tissue ex vivo by high‐definition optical coherence tomography (HD‐OCT) with the findings of frozen‐section histology in micrographic surgery.

Methods  Twenty freshly excised BCC were examined by HD‐OCT in the en‐face and slice imaging mode divided into four sections each in concordance with the four excision margins of histography, and subsequently processed for conventional micrographic evaluation.

Results  A total of 80 HD‐OCT images of 20 BCCs were evaluated and in 45% (9/20) HD‐OCT correlated perfectly with the histography results. The sensitivity and specificity for the 80 evaluated HD‐OCT images were 74% and 64% respectively.

Conclusions  High‐definition optical coherence tomography allows the postoperative identification of BCC in excised tissue ex vivo, but has still limitations in the recognition of tumour margins in comparison with the micrographic evaluation of frozen sections.
mTOR: at the crossroads of aging, chaperones, and Alzheimer's disease
Authors: Gouras Gunnar K.
Published: December 2012

Read the full article ‘Over‐expression of heat shock factor 1 phenocopies the effect of chronic inhibition of TOR by rapamycin and is sufficient to ameliorate Alzheimer's‐like deficits in mice modeling the disease’ on doi: 10.1111/jnc.12080
Oral health‐related quality of life in patients with tooth wear
Authors: Papagianni C. E. , van der Meulen M. J. , Naeije M. , Lobbezoo F.
Published: December 2012

The aim of this study was to investigate the impact of tooth wear (TW) on patients' oral health‐related quality of life. A total of 198 participants were included in the study. They belonged to the following four different diagnostic categories: 51 patients with TW, 46 patients with painful temporomandibular disorders (TMD), 43 complete denture wearers and 58 healthy controls. The Dutch version of the Oral Health Impact Profile (OHIP‐NL) was used to assess the patients' oral health‐related quality of life. The results of the study show that patients with TW have an impaired oral health‐related quality of life compared with healthy controls (P < 0·001). Furthermore, the impact of TW and of edentulousness do not differ significantly, while both of these oral conditions seem to have a lower impact on quality of life compared with painful TMD (P < 0·05). It was concluded that TW has a negative impact on patients' quality of life. This impact is comparable with that of edentulousness.
Hydroxyurea therapy in sickle cell anemia patients aids to maintain oral fungal colonization balance
Authors: Salvia Ana Carolina Rodrigues Danzi , Figueiredo Maria Stella , Braga Josefina Aparecida Pellegrini , Pereira Daniel Freitas Alves , Brighenti Fernanda Lourenção , Koga‐Ito C. Y.
Published: December 2012

Background

The aim of this study was to evaluate the frequency of Candida species and presence of lesions in the oral cavity of patients with sickle cell anemia (SS).

Methods

The study included 30 patients diagnosed with sickle cell anemia and taking hydroxyurea for at least 90 days (SS/HU+); and 39 patients with sickle cell anemia and without hydroxyurea therapy (SS/HU−). Two control groups were constituted by healthy individuals matched to the test groups in age, gender, and oral conditions (C/HU+ for SS/HU+ and C/HU− for SS/HU−). Oral clinical examination and anamnesis were performed. Yeasts were collected by oral rinses and identified by API system. Antifungal susceptibility evaluation was performed according to the CLSI methodology. Data obtained for microorganisms counts were compared by Student's t test (SS/HU+ vs. C/HU+ and SS/HU− vs. C/HU−) using MINITAB for Windows 1.4. Significance level was set at 5%.

Results

No oral candidosis lesions were detected. Significant differences in yeasts counts were observed between SS/HU− group and the respective control, but there were no differences between SS/HU+ and C/HU+. Candida albicans was the most prevalent species in all groups. Candida famata was observed both in SS and control groups. Candida dubliniensis, Candida glabrata, Candida krusei, Candida tropicalis, Candida pelliculosa, and Candida parapsilosis were observed only in SS groups. Most strains were susceptible to all antifungal agents.

Conclusion

Hydroxyurea therapy seems to decrease candidal counts and resistance rate in sickle cell anemia patients. However, further studies should be conducted in the future to confirm this finding. Hydroxyurea therapy in sickle cell anemia patients maintains fungal species balance in oral cavity.
Atrial natriuretic peptide as a marker of heart failure in children with left ventricular volume overload
Authors: Kotby Alyaa A , Taman Khaled H , Sedky Heba Tallah A , Habeeb Nevin MM , El‐Hadidi Eman S , Yosseif Hanan S
Published: December 2012

Aim

To evaluate the role of atrial natriuretic peptide (ANP) in differentiating the aetiology of heart failure in children with left ventricular (LV) volume overload.

Methods

The study was conducted on 48 patients with LV volume overload (G one: rheumatic heart disease in failure; G2: compensated rheumatic heart disease; G3: congenital left to right shunt; and G4: dilated cardiomyopathy). Twelve healthy children served as a control group. New York Heart Association (NYHA) class, LV dimensions and functions using Vivid 7 dimensions were evaluated. Serum ANP was measured using the ELISA technique, before and 3 months after treatment with angiotensin converting enzyme inhibitor.

Results

ANP was raised in all patients as compared to controls (G one: 28.33 ± 5.78, G2: 26.5 ± 4.11, G3: 28.5 ± 6.6, G4: 29.25 ± 4.5 pg/mL, control group: 5.54 ± 1.4 pg/mL, P < 0.001 for all) and varied significantly between different NYHA classes regardless of the underlying cardiac lesion. It was significantly higher in group 1 than 2 (P < 0.05). It decreased significantly after treatment (G1: 15.3 ± 5.3, G2: 10.7 ± 2.5, G3: 11.5 ± 3.8, G4: 15.7 ± 10.7 pg/mL, P < 0.001). The rate of change of ANP correlated with that of LV end diastolic diameter (r = 0.3, P < 0.05) irrespective of the underlying cause.

Conclusion

ANP increases in cases of LV volume overload irrespective of the aetiology of heart failure. It can differentiate between children in quiescent state from those in clinical failure even in the absence of echocardiographically detectable systolic dysfunction. Furthermore, it can monitor LV remodelling with treatment.
Detection and Characterization of Phytoplasma Associated with Big Bud Disease of Tomato in China
Authors: Xu Xia , Mou Hai‐Qing , Zhu Shui‐Fang , Liao Xiao‐Lan , Zhao Wen‐Jun
Published: December 2012

Symptomatic tomato plants exhibiting big bud, proliferation and small leaves of lateral shoots, purplish top leaves, phyllody, enlarged pistils, hypertrophic calyxes and small and polygonal fruit were collected in Yunnan Province of China. Pleomorphic phytoplasma‐like bodies were observed in the phloem sieve tube elements of symptomatic plants by transmission electron microscopy. The presence of phytoplasma in collected samples was further analysed and identified by PCR and virtual computer‐simulated restriction fragment length polymorphism (virtual RFLP). A 1.2 kb product was amplified by PCR with universal primers R16F2n/R16R2. Sequence comparisons revealed that the tested strains shared 99% 16S rRNA gene sequence similarity with members of ‘Candidatus Phytoplasma aurantifolia’ (16SrII group). Phylogenetic and virtual RFLP analysis of the 16S rRNA gene sequences confirmed that the phytoplasma is a member of the 16SrII group. This is the first report of 16SrII group phytoplasma infecting tomato in China.
Reaction of Melon (Cucumis meloL.) Cultivars toMonosporascus cannonballus(Pollack &Uecker) and their Effect on Total Phenol, Total Protein and Peroxidase Activities
Authors: Salari Mohammad , Panjehkeh Naser , Nasirpoor Zahra , Abkhoo Javad
Published: December 2012

Eighteen melon cultivars were screened for resistance toMonosporascus cannonballusunder greenhouse conditions. The melon cultivars were grown in pasteurized sand, which had been inoculated with a high level (60CFUs/g of soil) ofM. cannonballusmycelium from culture. CultivarsNabijani,Sfidak khatdar,Sfidak bekhat,Ghandak,Mollamosai,Chappat,Hajmashallahi andShadgan were moderately resistant toM. cannonballusbut all other melon cultivars were moderately to highly susceptible (HS) to this pathogen. A second screening was performed for resistance toM. cannonballusunder greenhouse conditions. In the second screening, cultivarsNabijani,Sfidak khatdar,Sfidak bekhat,Ghandak,Mollamosai,Chappat,Hajmashallahi andShadgan were moderately resistant toM. cannonballus. To examine the melon resistance mechanism againstM. cannonballus,the activities of total phenol, total protein and peroxidase in two melon cultivarsNabijani (as resistant) and Khaghani (as susceptible) were determined at 0, 24, 48 and 72 h after inoculation. Inoculated resistant cultivar roots had always higher content of total phenol, total protein and peroxidase than the corresponding inoculated susceptible cultivar roots. The results indicated that there was a relationship between resistance inNabijani and accumulation of total phenol, total protein and peroxidase.
Hepatitis viruses (other than hepatitis B and C viruses) as causes of hepatocellular carcinoma: an update
Authors: Kew M. C.
Published: December 2012

Chronic hepatitis B and C virus infections are universally accepted as causes of hepatocellular carcinoma in humans. Hepatitis A and E viruses cause only acute self‐limiting infections of the liver. Of the remaining hepatitis viruses ‐ Delta hepatitis, hepatitis G (GB‐C), TT and SEN ‐ all have at some time been incriminated as causes of hepatocellular carcinoma. Delta hepatitis virus requires helper functions from hepatitis B virus to become invasive. Chronic Delta/hepatitis B viral co‐infection runs a more severe course than that resulting from chronic hepatitis B virus infection alone, with progression to cirrhosis being more likely and more rapid. A substantial majority of the early studies did not find an increased incidence of hepatocellular carcinoma in co‐infected individuals. But more recently, an increased incidence of the tumour has been recorded more often than no increase. Further studies are needed to draw a firm conclusion with regard to the hepatocarcinogenic effect of dual Delta/hepatitis B virus co‐infection. With one exception, no published study (of 13) has incriminated chronic infection with hepatitis G virus as a cause of hepatocellular carcinoma. The dissenting study, published in 1999, was the only one performed in the United States. Fewer studies of the hepatocarcinogenic effect of TT virus have been performed. Apart from one study, published in 1999, no convincing evidence is available that supports a causal role for TT virus in hepatocarcinogenesis. The exception was in Japanese patients with high hepatitis C viral loads but independent of chronic hepatitis C virus infection. No evidence has been produced to indicate that SEN virus causes hepatocellular carcinoma.
The 2‐methylcitrate cycle is implicated in the detoxification of propionate in Toxoplasma gondii
Authors: Limenitakis Julien , Oppenheim Rebecca D. , Creek Darren J. , Foth Bernardo J. , Barrett Michael P. , Soldati‐Favre Dominique
Published: December 2012

Toxoplasma gondii belongs to the coccidian subgroup of the Apicomplexa phylum. The Coccidia are obligate intracellular pathogens that establish infection in their mammalian host via the enteric route. These parasites lack a mitochondrial pyruvate dehydrogenase complex but have preserved the degradation of branched‐chain amino acids (BCAA) as a possible pathway to generate acetyl‐CoA. Importantly, degradation of leucine, isoleucine and valine could lead to concomitant accumulation of propionyl‐CoA, a toxic metabolite that inhibits cell growth. Like fungi and bacteria, the Coccidia possess the complete set of enzymes necessary to metabolize and detoxify propionate by oxidation to pyruvate via the 2‐methylcitrate cycle (2‐MCC). Phylogenetic analysis provides evidence that the 2‐MCC was acquired via horizontal gene transfer. In T. gondii tachyzoites, this pathway is split between the cytosol and the mitochondrion. Although the rate‐limiting enzyme 2‐methylisocitrate lyase is dispensable for parasite survival, its substrates accumulate in parasites deficient in the enzyme and its absence confers increased sensitivity to propionic acid. BCAA is also dispensable in tachyzoites, leaving unresolved the source of mitochondrial acetyl‐CoA.
Interocular differences in visual latency induced by reduced‐aperture monovision
Authors: Plainis Sotiris , Petratou Dionysia , Giannakopoulou Trisevgeni , Radhakrishnan Hema , Pallikaris Ioannis G , Charman W Neil
Published: December 2012

Purpose

To explore the interocular differences in the temporal responses of the eyes induced by the monocular use of small‐aperture optics designed to aid presbyopes by increasing their depth‐of‐focus.

Methods

Monocular and binocular pattern‐reversal visual evoked potentials (VEPs) were measured at a mean photopic field luminance of 30 cd/m2 in seven normal subjects with either natural pupils or when the non‐dominant eye wore a small‐aperture contact lens (aperture diameter 1.5, 2.5 or 3.5 mm, or an annular opaque stop of inner and outer diameters 1.5 and 4.0 mm respectively). Responses were also measured with varying stimulus luminance (5, 13.9, 27.2 and 45 cd/m2) and a fixed 3.0 mm artificial pupil.

Results

Mean natural pupil diameters were 4.7 and 4.4 mm under monocular and binocular conditions respectively. The small‐aperture contact lenses reduced the amplitude of the P100 component of the VEP and increased its latency. Inter‐ocular differences in latency rose to about 20–25 ms when the pupil diameter of the non‐dominant eye was reduced to 1.5 mm. The measurements with fixed pupil and varying luminance suggested that the observed effects were explicable in terms of the changes in retinal illuminance produced by the restrictions in pupil area.

Conclusions

The anisocoria induced by small‐aperture approaches to aid presbyopes produces marked interocular differences in visual latency. The literature of the Pulfrich effect suggests that such differences can lead to distortions in the perception of relative movement and, in some cases, to possible hazard.
Reducing saturated fatty acids in Arabidopsis seeds by expression of a Caenorhabditis elegans 16:0–specific desaturase
Authors: Fahy Deirdre , Scheer Barbara , Wallis James G. , Browse John
Published: December 2012

Plant oilseeds are a major source of nutritional oils. Their fatty acid composition, especially the proportion of saturated and unsaturated fatty acids, has important effects on human health. Because intake of saturated fats is correlated with the incidence of cardiovascular disease and diabetes, a goal of metabolic engineering is to develop oils low in saturated fatty acids. Palmitic acid (16:0) is the most abundant saturated fatty acid in the seeds of many oilseed crops and in Arabidopsis thaliana. We expressed FAT–5, a membrane‐bound desaturase cloned from Caenorhabditis elegans, in Arabidopsis using a strong seed‐specific promoter. The FAT‐5 enzyme is highly specific to 16:0 as substrate, converting it to 16:1∆9; expression of fat‐5 reduced the 16:0 content of the seed by two‐thirds. Decreased 16:0 and elevated 16:1 levels were evident both in the storage and membrane lipids of seeds. Regiochemical analysis of phosphatidylcholine showed that 16:1 was distributed at both positions on the glycerolipid backbone, unlike 16:0, which is predominately found at the sn‐1 position. Seeds from a plant line homozygous for FAT–5 expression were comparable to wild type with respect to seed set and germination, while oil content and weight were somewhat reduced. These experiments demonstrate that targeted heterologous expression of a desaturase in oilseeds can reduce the level of saturated fatty acids in the oil, significantly improving its nutritional value.
Giant Congenital Melanocytic Nevus with Cartilaginous Differentiation
Authors: de Blacam Catherine , Mc Dermott Michael , O'Donovan David
Published: December 2012

We report the unusual presence of a benign focus of cartilage in an excised portion of giant congenital melanocytic nevus.
Orphan Rocker Tracks: A Variant of Friction Melanosis in an Institutionalized Child
Authors: Diamond Gary , Amitai Dan Ben
Published: December 2012

Friction melanosis is an acquired pigmentary disorder consisting of diffuse, brown pigmentation resulting from repeated rubbing of affected areas of the skin. An institutionalized child whose lower back was subjected to intense and repeated rocking displayed the characteristic lesions.
Predictive value of clinical chorioamnionitis in extremely premature infants
Authors: Tokumasu Hironobu , Hinotsu Shiro , Kita Fumiyo , Kawakami Koji
Published: December 2012

Background

Clinical chorioamnionitis and histological chorioamnionitis are important risk factors for neonatal complications and neurodevelopmental impairment in premature infants. It is unclear, however, whether a diagnosis of clinical chorioamnionitis is sufficient to establish a diagnosis of histological chorioamnionitis. The aim of this study was to evaluate the predictive value of clinical chorioamnionitis in the diagnosis of histological chorioamnionitis in extremely premature infants.

Methods

This study was a secondary analysis of data from the Neonatal Research Network in Japan, a population‐based cohort study aimed at identifying the clinical characteristics and morbidity of very low‐birthweight infants. Data for extremely premature infants <28 weeks' gestational age from 2003 to 2007, were used. Subset analysis investigated positive predictive value by gestational age.

Results

Of the 2470 infants analyzed, 786 were diagnosed with clinical chorioamnionitis and 1129 with histological chorioamnionitis. The positive predictive value of clinical chorioamnionitis for histological chorioamnionitis was 86.6% (681/786; 95% confidence interval [CI]: 84.4–88.6%), sensitivity was 60.3% (681/1129; 95%CI: 58.8–61.7%), and specificity was 92.2% (1236/1341; 95%CI: 90.9–93.3%). In subset analysis, the positive predictive value was particularly high at 23 weeks of gestation (89.1%; 115/129), with sensitivity of 65.3% (115/176) and specificity of 89.6% (120/134).

Conclusions

The finding that clinical chorioamnionitis is a useful predictor of histological chorioamnionitis provides important insights into the relationship between these two diagnoses, and has important implications in determining the appropriate timing of delivery of extremely premature infants.
The modality‐specific contribution of peptidergic and non‐peptidergic nociceptors is manifest at the level of dorsal horn nociresponsive neurons
Authors: Zhang Jie , Cavanaugh Daniel J. , Nemenov Michael I. , Basbaum Allan I.
Published: December 2012

Key points

Ablation of TRPV1+/peptidergic or of MrgprD+/non‐peptidergic nociceptors produces modality‐specific deficits in the behavioural responses to heat and mechanical stimuli, respectively. Noxious heat‐induced dorsal horn Fos expression is also eliminated, despite the heat responsiveness of the non‐peptidergic nociceptors.

To assess whether this modality‐specific contribution is manifest at the level of individual spinal neurons, we made extracellular recordings from mouse dorsal horn after selective ablation of the two nociceptor populations.

Intrathecal capsaicin, which ablated the TRPV1+ nociceptors, abolished responsiveness of superficial and deep dorsal horn neurons to noxious heat, with no change in response to noxious mechanical stimulation.

Ablation of MrgprD+ afferents did not alter the response to noxious heat but reduced the firing of dorsal horn neurons in response to noxious mechanical stimulation.

These findings argue strongly that TRPV1+ and MrgprD+ nociceptors provide modality‐specific contributions to the response properties of spinal cord neurons.

Abstract  We previously demonstrated that genetic and/or pharmacological ablation of the TRPV1+/peptidergic or the MrgprD+/non‐peptidergic subset of nociceptors produced selective, modality‐specific deficits in the behavioural responses to heat and mechanical stimuli, respectively. To assess whether this modality‐specific contribution is also manifest at the level of spinal cord neuron responsiveness, here we made extracellular recordings from lumbar dorsal horn neurons of the mouse in response to graded thermal and mechanical stimulation. We found that, following intrathecal injection of capsaicin to eliminate the central terminals of TRPV1+ nociceptors, neurons in the region of laminae I and V of the spinal cord lost responsiveness to noxious heat (whether generated by a contact heat probe or diode laser), with no change in their response to noxious mechanical stimulation. In contrast, ablation of MrgprD+ afferents did not alter the response to noxious heat, but reduced the firing of superficial dorsal horn nociceptive‐specific neurons in response to graded mechanical stimulation and decreased the relative number of wide dynamic range neurons that were exclusively mechanosensitive. Neither ablation procedure reduced the number of dorsal horn neurons that responded to noxious cold. These findings support the conclusion that TRPV1+ nociceptors are necessary and probably sufficient for noxious heat activation of dorsal horn neurons and that, despite their polymodal properties, TRPV1+ and MrgprD+ nociceptors provide modality‐specific contributions to the response properties of spinal cord neurons.
Effects of voluntary wheel running on the kidney at baseline and after ischaemia–reperfusion‐induced acute kidney injury: a strain difference comparison
Authors: Moningka Natasha C. , Cunningham, Jr Mark W. , Sterling Myrline , West Crystal A. , Verlander Jill W. , Croker Byron P. , Ahlgren Joslyn , Hayward Linda , Baylis Chris
Published: December 2012

Key points

The impact of exercise on functional proteins critical for proper blood vessel health in the kidney is not well understood.

Using rats of different genetic backgrounds, we studied how chronic exercise affects the abundance of specific blood vessel proteins in the kidney, and whether this has any impact on the rat's susceptibility to acute kidney injury.

We found that the renal response to exercise is dependent on genetic background, and that in one strain exercise rendered the kidney more vulnerable to acute kidney injury.

The vulnerable rats exhibited exercise‐dependent loss of the protective renal proteins critical for proper blood vessel health, while the protected strain showed increases in these protective proteins.

Our findings are particularly relevant regarding exercise prescription to kidney disease patients.

Abstract  Exercise‐induced vascular endothelial adaptations in the kidney are not well understood. Therefore, we investigated the impact of voluntary wheel running (VWR) on the abundance of endothelial nitric oxide synthase (eNOS) and extracellular superoxide dismutase (EC SOD), in kidney and lung, and other SOD isoforms and total antioxidant capacity (TAC), in kidney. We also determined whether VWR influences susceptibility to acute kidney injury (AKI). Male Sprague–Dawley and Fisher 344 rats, VWR or sedentary for 12 weeks, were subjected to AKI (uninephrectomy (UNX) and 35 min of left kidney ischaemia–24 h reperfusion, IR). We measured glomerular filtration rate (GFR) and renal plasma flow (RPF), and analysed renal structural injury. Running was comparable between strains and VWR reduced body weight. In Sprague–Dawley rats, VWR reduced eNOS and EC SOD, but increased Mn SOD in kidney. Similar changes were seen after 6 weeks of VWR in Sprague–Dawley rats. In Fisher 344 rats, VWR increased eNOS, all SOD isoforms and TAC in kidney. Both strains increased eNOS and EC SOD in lung with VWR. Compared to UNX alone, UNX‐IR injury markedly reduced renal function for both strains; however, in the Sprague–Dawley rats, VWR exacerbated falls in GFR and RPF due to UNX‐IR, whereas in the Fisher 344 rats, GFR was unaffected by VWR. Some indices of renal structural injury due to UNX‐IR tended to be worse in SD vs. F344. Our study demonstrates that genetic background influences the effect of exercise on kidney eNOS and EC SOD, which in turn influence the susceptibility to AKI.
Gastric vagal afferent modulation by leptin is influenced by food intake status
Authors: Kentish Stephen J. , O'Donnell Tracey A. , Isaacs Nicole J. , Young Richard L. , Li Hui , Harrington Andrea M. , Brierley Stuart M. , Wittert Gary A. , Blackshaw L. Ashley , Page Amanda J.
Published: December 2012

Key points

Obesity occurs when energy intake exceeds expenditure, and the excess energy is stored as fat.

We show that, after a 14 h food deprivation or 12 weeks consumption of a high‐fat diet, gastric vagal afferent responses to mechanical stimulation in the presence of the satiety peptide leptin are altered.

Leptin has an excitatory effect on gastric mucosal vagal afferents, which is abolished after food restriction or prolonged excess.

In contrast, leptin has an inhibitory effect on gastric tension‐sensitive afferents, but only after food restriction or energy excess conditions.

These changes in the response to leptin in the stomach, after food restriction or prolonged high‐fat feeding, occur in such a manner as to facilitate an increase in food intake in both conditions.

Abstract  Energy intake is strongly influenced by vagal afferent signals from the stomach, and is also modulated by leptin. Leptin may be secreted from gastric epithelial cells, so we aimed to determine the direct effect of leptin on gastric vagal afferents under different feeding conditions. Female C57BL/6 mice were fed standard laboratory diet, high‐fat diet or were food restricted. The expression of leptin receptor (Lep‐R) and its signal transduction molecules in vagal afferents was determined by retrograde tracing and reverse‐transcription polymerase chain reaction, and the relationship between leptin‐immunopositive cells and gastric vagal afferent endings determined by anterograde tracing and leptin immunohistochemistry. An in vitro preparation was used to determine the functional effects of leptin on gastric vagal afferents and the second messenger pathways involved. Leptin potentiated vagal mucosal afferent responses to tactile stimuli, and epithelial cells expressing leptin were found close to vagal mucosal endings. After fasting or diet‐induced obesity, potentiation of mucosal afferents by leptin was lost and Lep‐R expression reduced in the cell bodies of gastric mucosal afferents. These effects in diet‐induced obese mice were accompanied by a reduction in anatomical vagal innervation of the gastric mucosa. In striking contrast, after fasting or diet‐induced obesity, leptin actually inhibited responses to distension in tension receptors. The inhibitory effect on gastric tension receptors was mediated through phosphatidylinositol 3‐kinase‐dependent activation of large‐conductance calcium‐activated potassium channels. The excitatory effect of leptin on gastric mucosal vagal afferents was mediated by phospholipase C‐dependent activation of canonical transient receptor potential channels. These data suggest the effect of leptin on gastric vagal afferent excitability is dynamic and related to the feeding state. Paradoxically, in obesity, leptin may reduce responses to gastric distension following food intake.
Infant satiety depends on transient expression of cholecystokinin‐1 receptors on ependymal cells lining the third ventricle in mice
Authors: Ozaki Tomoya , Mohammad Shahid , Morioka Eri , Takiguchi Soichi , Ikeda Masayuki
Published: December 2012

Key points

In mammals, satiety‐controlling mechanisms develop before the switch from ingestive behaviour from milk suckling to regular food intake; however, the underlying mechanisms are currently unknown.

We show that absence of the cholecystokinin‐1 (CCK‐1) receptor gene significantly increases suckling pup weight, regardless of maternal genotype in mice.

CCK‐1 receptor expression was observed in satiety‐controlling regions such as the hypothalamus, caudal brainstem, nodose ganglion and pylorus, which is consistent with suggested receptor function in adults, whereas corresponding receptor expression was low to non‐existent at pre‐weanling stages.

Third ventricle ependymal tanycyte‐like cells transiently expressed CCK‐1 receptors at critical developmental stages, and gastrointestinal milk filling upregulated cFos expression in these cells.

Localized blocking of ependymal CCK‐1 receptors was sufficient to produce overweight pups, suggesting that the ependymal CCK‐1 receptor is an infant‐specific satiety controller.

Abstract  Cholecystokinin (CCK) is a hypothetical controller for suckling and infancy body weight, although the underlying mechanisms remain unclear. Therefore, the present study analysed the mechanisms using mice lacking the CCK‐1 receptor (CCK1R–/–). Although CCK1R–/– mice displayed normal weights at birth and adulthood, CCK1R–/– pups had enlarged adipocytes and were overweight from the first to second week after birth, regardless of maternal genotype. The lacZ reporter gene assay and/or calcium imaging analysis demonstrated that CCK‐1 receptors were abundant in satiety‐controlling regions such as the hypothalamus, brainstem, nodose ganglion and pylorus in adults, whereas these signals were few to lacking at pre‐weanling stages. At postnatal day (PD) 6, the increase in cFos expression in the medullary nucleus tractus solitarius was similarly triggered by gastrointestinal milk‐ or saline filling in both genotypes, further indicating immature CCK‐1 receptor function in an ascending satiety‐controlling system during infancy. Conversely, third ventricle ependymal tanycyte‐like cells expressed CCK‐1 receptors with expression peaking at PD6. At PD6, wild‐type but not CCK1R–/– mice had increased cFos immunoreactivity in ependymal cells following gastrointestinal milk filling whereas the response became negligible at PD12. In addition, ependymal cFos was not increased by saline filling, indicating that these responses are dependent on CCK‐1 receptors, developmental stage and nutrients. Furthermore, body weights of wild‐type pups were transiently increased by blocking ependymal CCK receptor function with microinjection of a CCK‐1 antagonist, but not a CCK‐2 antagonist. Hence, we demonstrate de novo functions of ependymal CCK‐1 receptors and reveal a new aspect of infant satiety‐controlling mechanisms.
Distinct roles of GABAB1a‐ and GABAB1b‐containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity
Authors: Craig Michael T. , Mayne Elizabeth W. , Bettler Bernhard , Paulsen Ole , McBain Chris J.
Published: December 2012

Key points

GABAB receptors containing the GABAB1a subunit contribute to spontaneous termination of UP states.

GABAB receptors containing the GABAB1b subunit are essential for afferent‐evoked termination of UP states.

Abstract  During slow‐wave sleep, cortical neurons display synchronous fluctuations between periods of persistent activity (‘UP states’) and periods of relative quiescence (‘DOWN states’). Such UP and DOWN states are also seen in isolated cortical slices. Recently, we reported that both spontaneous and evoked termination of UP states in slices from the rat medial entorhinal cortex (mEC) involves GABAB receptors. Here, in order to dissociate the roles of GABAB1a‐ and GABAB1b‐containing receptors in terminating UP states, we used mEC slices from mice in which either the GABAB1a or the GABAB1b subunit had been genetically ablated. Pharmacological blockade of GABAB receptors using the antagonist CGP55845 prolonged the UP state duration in both wild‐type mice and those lacking the GABAB1b subunit, but not in those lacking the GABAB1a subunit. Conversely, electrical stimulation of layer 1 could terminate an ongoing UP state in both wild‐type mice and those lacking the GABAB1a subunit, but not in those lacking the GABAB1b subunit. Together with previous reports, indicating a preferential presynaptic location of GABAB1a‐ and postsynaptic location of GABAB1b‐containing receptors, these results suggest that presynaptic GABAB receptors contribute to spontaneous DOWN state transitions, whilst postsynaptic GABAB receptors are essential for the afferent termination of the UP state. Inputs to layer 1 from other brain regions could thus provide a powerful mechanism for synchronizing DOWN state transitions across cortical areas via activation of GABAergic interneurons targeting postsynaptic GABAB receptors.
α1A‐Adrenergic regulation of inhibition in the olfactory bulb
Authors: Zimnik Nathan C. , Treadway Tyler , Smith Richard S. , Araneda Ricardo C.
Published: December 2012

Key points

Here, in mouse brain slices, we examined the cellular effects of noradrenaline to better understand its influence on olfactory bulb processing.

β‐ and α1‐adrenergic receptor activation increases GABA currents in mitral cells in an age‐dependent manner; the β‐adrenergic effect is prominent only during early postnatal weeks, while the α1 effect is present at all ages.

This study focused on the α1‐mediated increase in GABA inhibitory currents in mitral cells and found noradrenaline acts on the α1A‐adrenergic receptor subtype to produce long‐lasting excitation of granule cells.

The enhancement of inhibition by noradrenaline was consistent across a broad concentration range; at all concentrations, noradrenaline increased inhibitory currents in mitral cells.

Our studies highlight the important role of α1A‐adrenergic receptor subtypes in increasing inhibition at dendrodendritic synapses, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviours.

Abstract  By regulating inhibition at dendrodendritic synapses between mitral and granule cells (GCs), noradrenergic neurons extending from the brainstem provide an input essential for odour processing in the olfactory bulb (OB). In the accessory OB (AOB), we have recently shown that noradrenaline (NA) increases GABA inhibitory input on to mitral cells (MCs) by exciting GCs. Here, we show that GCs in the main OB (MOB) exhibit a similar response to NA, indicating a common mechanism for noradrenergic regulation of GC→MC inhibition throughout the OB. In GCs of the MOB, NA (10 μm) produced a robust excitatory effect that included a slow afterdepolarization that followed a train of action potentials evoked by a current stimulus. The depolarization and slow afterdepolarization in GCs were blocked by the α1A‐adrenergic receptor (AR) selective antagonist WB 4101 (30 nm) and mimicked by the α1A‐AR selective agonist A 61603 (1 μm). In recordings from MCs, A 61603 (30 nm–1 μm) produced a sizeable increase in the frequency of spontaneous and miniature IPSCs, an effect completely abolished by the GABAA receptor antagonist gabazine (5 μm). Likewise, activation of β‐ARs increased the frequency of spontaneous IPSCs; however, this effect was smaller and confined to the first postnatal weeks. NA enhanced inhibition in MCs across a broad concentration range (0.1–30 μm) and its effects were completely abolished by a mixture of α1‐ and β‐AR antagonists (1 μm prazosin and 10 μm propranolol). Furthermore, the general α2‐AR agonist clonidine (10 μm) failed to affect sIPSC frequency. Thus, the NA‐mediated increase in GC→MC inhibition in the OB results mostly from activation of the α1A‐AR subtype.