bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Characterization of a Conserved, Calcium-Dependent Periplasmic Protease from Legionella pneumophila
Authors: Chatterjee Debashree , Boyd Chelsea D. , O'Toole George A. , Sondermann Holger
Published: June 2012

The bacterial dinucleotide second messenger c-di-GMP has emerged as a central molecule in regulating bacterial behavior, including motility and biofilm formation. Proteins for the synthesis and degradation of c-di-GMP and effectors for its signal transmission are widely used in the bacterial domain. Previous work established the GGDEF-EAL domain-containing receptor LapD as a central switch inPseudomonas fluorescenscell adhesion. LapD senses c-di-GMP inside the cytosol and relays this signal to the outside by the differential recruitment of the periplasmic protease LapG. Here we identify the core components of an orthologous system inLegionella pneumophila. Despite only moderate sequence conservation at the protein level, key features concerning the regulation of LapG are retained. The output domain of the LapD-like receptor fromL. pneumophila, CdgS9, binds the LapG ortholog involving a strictly conserved surface tryptophan residue. While the endogenous substrate forL. pneumophilaLapG is unknown, the enzyme processed the correspondingP. fluorescenssubstrate, indicating a common catalytic mechanism and substrate recognition. Crystal structures ofL. pneumophilaLapG provide the first atomic models of bacterial proteases of the DUF920 family and reveal a conserved calcium-binding site important for LapG function.
LapG, Required for Modulating Biofilm Formation by Pseudomonasfluorescens Pf0-1, Is a Calcium-Dependent Protease
Authors: Boyd Chelsea D. , Chatterjee Debashree , Sondermann Holger , O'Toole George A.
Published: June 2012

Biofilm formation by
Pseudomonas
fluorescens
Pf0-1 requires the cell surface adhesin LapA. We previously reported that LapG, a periplasmic cysteine protease of
P. fluorescens
, cleaves the N terminus of LapA, thus releasing this adhesin from the cell surface and resulting in loss of the ability to make a biofilm. The activity of LapG is regulated by the inner membrane-localized cyclic-di-GMP receptor LapD via direct protein-protein interactions. Here we present chelation and metal add-back studies demonstrating that calcium availability regulates biofilm formation by
P. fluorescens
Pf0-1. The determination that LapG is a calcium-dependent protease, based on
in vivo
and
in vitro
studies, explains the basis of this calcium-dependent regulation. Based on the crystal structure of LapG of
Legionella
pneumophila
in the accompanying report by Chatterjee and colleagues (D. Chatterjee et al., J. Bacteriol. 194:4415–4425, 2012), we show that the calcium-binding residues of LapG, D134 and E136, which are near the critical C135 active-site residue, are required for LapG activity of
P. fluorescens
in vivo
and
in vitro
. Furthermore, we show that mutations in D134 and E136 result in LapG proteins no longer able to interact with LapD, indicating that calcium binding results in LapG adopting a conformation competent for interaction with the protein that regulates its activity. Finally, we show that citrate, an environmentally relevant calcium chelator, can impact LapG activity and thus biofilm formation, suggesting that a physiologically relevant chelator of calcium can impact biofilm formation by this organism.
Influence of Herpes Simplex Virus 1 Latency-Associated Transcripts on the Establishment and Maintenance of Latency in the ROSA26R Reporter Mouse Model
Authors: Nicoll M. P. , Proença J. T. , Connor V. , Efstathiou S.
Published: June 2012

Herpes simplex virus 1 (HSV-1) can establish life-long latent infection in sensory neurons, from which periodic reactivation can occur. During latency, viral gene expression is largely restricted to the latency-associated transcripts (LATs). While not essential for any phase of latency, to date the LATs have been shown to increase the efficiency of both establishment and reactivation of latency in small-animal models. We sought to investigate the role of LAT expression in the frequency of latency establishment within the ROSA26R reporter mouse model utilizing Cre recombinase-encoding recombinant viruses harboring deletions of the core LAT promoter (LAP) region. HSV-1 LAT expression was observed to influence the number of latently infected neurons in trigeminal but not dorsal root ganglia. Furthermore, the relative frequencies of latency establishment of LAT-positive and LAT-negative viruses are influenced by the inoculum dose following infection of the mouse whisker pads. Finally, analysis of the infected cell population at two latent time points revealed a relative loss of latently infected cells in the absence of LAT expression. We conclude that the HSV-1 LATs facilitate the long-term stability of the latent cell population within the infected host and that interpretation of LAT establishment phenotypes is influenced by infection methodology.
Avoiding handover fumbles: a controlled trial of a structured handover tool versus traditional handover methods
Authors: Payne Christina E , Stein Jason M , Leong Traci , Dressler Daniel D
Published: June 2012

Background

Handover of patient information represents a critical time period during a patient's hospitalisation. While recent guidelines promote standardised communication during these patient care transitions, significant variability in structure and practice persists among hospitals and providers.

Methods

The authors surveyed internal medicine residents regarding handover practices before and after introduction of a structured, web-based handover application. The handover application standardised patient data in a format suitable for both patient handovers and day-to-day patient management.

Results

A total of 80 residents were surveyed prior to the intervention (80% response rate) and 161 residents during the intervention (average 68% response rate for all surveys distributed). At baseline, residents perceived deficits in handover practices related to the variability of information transferred and correlated that variability to near-miss events. After introduction of the handover application, 100% of handovers contained an updated problem list, active medications, and code status (compared to <55% at baseline, p<0.01); residents perceived approximately half as many near-miss events on call (31.5% vs 55%; p=0.0341) and were twice as likely to respond that they were confident or very confident in their patient handovers compared to traditional practices (93% vs 49%; p=0.01).

Conclusion

Standardisation of information transmitted during patient handovers through the use of a structured, web-based application led to consistent transfer of vital patient information and was associated with improved resident confidence and fewer perceived near-miss events on call.
Impact of online education on intern behaviour around joint commission national patient safety goals: a randomised trial
Authors: Shaw Tim J , Pernar Luise I , Peyre Sarah E , Helfrick John F , Vogelgesang Kaitlin R , Graydon-Baker Erin , Chretien Yves , Brown Elizabeth J , Nicholson James C , Heit Jeremy J , Co John Patrick T , Gandhi Tejal
Published: June 2012

Purpose

To compare the effectiveness of two types of online learning methodologies for improving the patient-safety behaviours mandated in the Joint Commission National Patient Safety Goals (NPSG).

Methods

This randomised controlled trial was conducted in 2010 at Massachusetts General Hospital and Brigham and Women's Hospital (BWH) in Boston USA. Incoming interns were randomised to either receive an online Spaced Education (SE) programme consisting of cases and questions that reinforce over time, or a programme consisting of an online slide show followed by a quiz (SQ). The outcome measures included NPSG-knowledge improvement, NPSG-compliant behaviours in a simulation scenario, self-reported confidence in safety and quality, programme acceptability and programme relevance.

Results

Both online learning programmes improved knowledge retention. On four out of seven survey items measuring satisfaction and self-reported confidence, the proportion of SE interns responding positively was significantly higher (p<0.05) than the fraction of SQ interns. SE interns demonstrated a mean 4.79 (36.6%) NPSG-compliant behaviours (out of 13 total), while SQ interns completed a mean 4.17 (32.0%) (p=0.09). Among those in surgical fields, SE interns demonstrated a mean 5.67 (43.6%) NPSG-compliant behaviours, while SQ interns completed a mean 2.33 (17.9%) (p=0.015). Focus group data indicates that SE was more contextually relevant than SQ, and significantly more engaging.

Conclusion

While both online methodologies improved knowledge surrounding the NPSG, SE was more contextually relevant to trainees and was engaging. SE impacted more significantly on both self-reported confidence and the behaviour of surgical residents in a simulated scenario.
Anaesthetic drug administration as a potential contributor to healthcare-associated infections: a prospective simulation-based evaluation of aseptic techniques in the administration of anaesthetic drugs
Authors: Gargiulo Derryn A , Sheridan Janie , Webster Craig S , Swift Simon , Torrie Jane , Weller Jennifer , Henderson Kaylene , Hannam Jacqueline , Merry Alan F
Published: June 2012

Objective

To evaluate the possibility that anaesthetists are administering potentially pathogenic micro-organisms to their patients.

Design

Prospective microbiological and observational study in a realistic simulated setting.

Participants

Ten anaesthetists supported by 10 anaesthetic technicians.

Primary outcome measure

The presence or absence of organisms cultured from sterile intravenous bags used to collect drugs injected during the simulated cases and from the needles and the contents of the syringes used. The authors also observed the aseptic techniques used.

Results

Organisms were isolated from five of 38 (13%) bags from five of 20 simulated cases anaesthetised by four of 10 anaesthetists, 10 of 197 (5%) syringes and six of 17 (35%) needles. None of the anaesthetists washed their hands prior to entry, used the hand gel provided, disinfected the phial septa before drawing up drugs or disinfected the intravenous ports on the intravenous administration set before use. One was seen to recap a needle left on a syringe for possible reuse. Three participants were observed to place equipment such as stethoscopes, drug charts and pens on top of their inuse drug trays.

Conclusion

The administration of intravenous drugs during anaesthesia may be an important factor in the genesis (or potentially the prevention) of healthcare-associated infection. These observations suggest room for improvement in the aseptic techniques of at least some anaesthetists when preparing and administering intravenous drugs. Confirmation of these findings in clinical settings is needed.

Study registry number (for the VASER study)

Australian New Zealand Clinical Trials Registry: Ref: ACTRN 12609000530224,https://www.anzctr.org.au/registry/trial_review.aspx?ID=308128; note that the work presented here is a subset of the registered trial and its outcomes were not included in this registration.
Out-of-hospital cardiac arrest in Cork, Ireland
Authors: Henry Kieran , Murphy Adrian , Willis David , Cusack Stephen , Bury Gerard , O'Sullivan Iomhar , Deasy Conor
Published: June 2012

Background

Out-of-hospital cardiac arrest (OHCA) in Ireland accounts for approximately 5000 deaths annually. Little published evidence exists on survival from OHCA in this country to date. We aimed to characterise and describe ‘presumed cardiac’ OHCA in Cork City and County attended by the Ambulance Service.

Methods

Dispatch records, ambulance patient records and hospital records for a 1-year period were examined for patient demographics, OHCA characteristics, interventions and patient outcomes.

Results

There were 231 ‘presumed cardiac’ OHCAs attended over the study period; 130 (56%) were in urban locations and 101 (44%) in rural. OHCAs were lay-witnessed in 20% (n=46), and 22% (n=50) received bystander CPR. Shockable rhythm was present in 36 cases (16%) on initial assessment, and there was no difference in presence of shockable rhythm between urban and rural OHCAs (18% vs 13%, p=0.31). Resuscitation was attempted in 176 cases (77.5%), of whom 27 (15%) achieved return of spontaneous circulation and 13 (7.4%) survived to leave hospital. Survival when the initial rhythm was shockable was 16.7% (6 of 36 patients). Despite longer response times for rural compared with urban OHCAs (median (IQR) 16.5 (11.0–23.5) vs 9 (7–12) min, p<0.001), survival to leave hospital alive where resuscitation was attempted was similar (7.4% vs 7.4%, p=0.99, respectively).

Conclusion

A survival rate of 16.7% in shockable rhythms indicates scope for improvement which would influence the overall survival rate which was found to be 7.4%. Real-time feedback of performance and quality of the continuum of patient care through a clinical-quality cardiac arrest registry would monitor and incentivise such initiatives.
Improving the diagnosis of central nervous system infections in adults through introduction of a simple lumbar puncture pack
Authors: Michael Benedict Daniel , Powell Graham , Curtis Sarah , Bailey Lisa , Almond Solomon , McGill Fiona , Cousins David , Hart Ian J , Griffiths Michael , Kneen Rachel , Solomon Tom
Published: June 2012

Background

Acute central nervous system (CNS) infections, such as meningitis and encephalitis, are neurological emergencies for which accurate diagnosis and prompt treatment improve the outcome. Analysis of the cerebrospinal fluid (CSF) obtained at lumbar puncture (LP) is pivotal to establishing the diagnosis and guiding management. PCR analysis of the CSF is an important method to identify the pathogen. However, recent studies have demonstrated that many patients have inadequate CSF sample collection and analysis.

Aims

To increase the proportion of patients having an LP for a suspected CNS infection for whom the appropriate samples are taken. Secondary aims included to increase the proportion of patients for whom a pathogen was identified.

Methods

The authors developed an LP pack for patients with a suspected CNS infection. They also assessed its impact on diagnosis by comparing practice 6 months before and after its introduction to the medical admissions unit of a large inner city teaching hospital.

Results

The authors found that the LP pack reduced major errors in CSF sample collection and improved the diagnosis of acute CNS infections; among those patients who had a CSF pleocytosis, the proportion with a viral or bacterial pathogen identified by PCR was increased after introduction of the pack.

Discussion

This study has demonstrated that the introduction of a simple low-cost LP pack into a busy acute medical setting can improve the diagnosis of CNS infections and, thus, guide treatment. Further work is needed to see if these results are more widely reproducible, and to examine the clinical, health and economic impact on overall management of patients with suspected CNS infections.
Administration ofhyoscine- n-butylbromideduring colonoscopy: a survey of current UK practice: Table 1
Authors: Bedford Matthew Robert , Reuser Tristan , Wilson Paul , Karandikar Sharad , Bowley Douglas
Published: June 2012

Objective

Current British Society of Gastroenterology (BSG) guidelines suggest thathyoscine-n-butylbromide (Buscopan)should be avoided during colonoscopy in patients with a history of angle-closure glaucoma. Angle-closure glaucoma, however, is not very common, is asymptomatic before onset and is treated definitively by a single laser treatment (if spotted early). Open-angle glaucoma is not affected byhyoscine. The aim of this study was to assess the use ofhyoscineamong colonoscopists, with particular reference to glaucoma.

Design and setting

Following BSG endoscopy subcommittee approval, a short questionnaire was electronically administered to members of the BSG and the Association of Coloproctology of Great Britain and Ireland.

Main outcome measures

Hyoscineuse among colonoscopists, and effect of glaucoma history upon prescribing practice.

Results

188 colonoscopists responded to some or all of the questions. 123/183 (67.2%) of respondents claimed they were aware of the BSG guidelines. 160/187 (85.6%) sometimes or always usehyoscine, while 27/187 (14.4%) never do. 137/177 (77.4%) always enquire about glaucoma history prior to administration, although 147/176 (83.0%) make no differentiation between open-angle or angle-closure forms. 126/178 (70.8%) would (incorrectly) withholdhyoscineif the patient declares a history of any form of glaucoma. 140/179 (78.2%) do not substitute glucagon as an antispasmodic. 4/180 (2.2%) had encountered ophthalmic complications post-administration.

Conclusions

Current BSG guidelines pertaining tohyoscineuse and glaucoma are inappropriate; the authors recommend revision. Patients undergoing colonoscopy who have receivedhyoscineshould, instead, be advised to seek urgent medical advice if they develop ophthalmic symptoms.
Structural stigma, sex work and HIV: contradictions and lessons learnt from a community-led structural intervention in southern India
Authors: Biradavolu Monica Rao , Blankenship Kim M , Jena Asima , Dhungana Nimesh
Published: June 2012

Background

Recent theorisation has pushed stigma research in new directions, arguing for a need to challenge the unequal power relations that impact groups most at risk for HIV-related stigma rather than locate stigma in the individual. Such a conceptualisation resonates with the growing emphasis on structural interventions for HIV prevention that attempt to alter the social context of risk.

Methods

The paper predominantly relies on longitudinal interviews conducted three times over a 2-year period with sex workers with varying degrees of involvement with the non-governmental organisation (NGO) and community-based organisation.

Results

Recognising that stigma is socially constructed and structurally reproduced, the NGO helped mobilise marginalised and hitherto scattered female sex workers to form community-based organisations to challenge their disadvantaged status in society. The authors show how stigma alleviation strategies presented a contradiction: emboldening one group of female sex workers to self-identify as sex workers while making others reluctant to access the intervention-run clinic.

Conclusion

The paper builds on a growing body of research that acknowledges the struggles in implementing structural interventions, particularly for NGOs working in regions with a diverse population of sex workers with varying needs. The authors argue that intervention goals of reducing stigma and increasing the use of sexually transmitted infection services do not have to conflict and, in fact, must go hand-in-hand for an implementation to be considered astructuralintervention.
Standard of practice: endovascular treatment of intracranial atherosclerosis: Table 1
Authors: Hussain M Shazam , Fraser Justin F , Abruzzo Todd , Blackham Kristine A , Bulsara Ketan R , Derdeyn Colin P , Gandhi Chirag D , Hirsch Joshua A , Hsu Daniel P , Jayaraman Mahesh V , Meyers Philip M , Narayanan Sandra , Prestigiacomo Charles J , Rasmussen Peter A
Published: June 2012

Background

Symptomatic intracranial atherosclerotic disease (ICAD) worldwide represents one of the most prevalent causes of stroke. When severe, studies show that it has a very high risk for recurrent stroke, highlighting the need for effective preventative strategies. The mainstay of treatment has been medical therapy and is of critical importance in all patients with this disease. Endovascular therapy is also a possible therapeutic option but much remains to be defined in terms of best techniques and patient selection. This guideline will serve as recommendations for diagnosis and endovascular treatment of patients with ICAD.

Methods

A literature review was performed to extract published literature regarding ICAD, published from 2000 to 2011. Evidence was evaluated and classified according to American Heart Association (AHA)/American Stroke Association standard. Recommendations are made based on available evidence assessed by the Standards Committee of the Society of NeuroInterventional Surgery. The assessment was based on guidelines for evidence based medicine proposed by the American Academy of Neurology (AAN), the Stroke Council of the AHA and the University of Oxford, Centre for Evidence Based Medicine (CEBM).

Results

59 publications were identified. The SAMMPRIS study is the only prospective, randomized, controlled trial available and is given an AHA level B designation, AAN class II and CEBM level 1b. The Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial arteries (SSYLVIA) trial was a prospective, non-randomized study with the outcome assessment made by a non-operator study neurologist, allowing an AHA level B, AAN class III and CEBM level 2. The remaining studies were uncontrolled or did not have objective outcome measurement, and are thus classified as AHA level C, AAN class IV and CEBM level 4.

Conclusion

Medical management with combination aspirin and clopidogrel for 3 months and aggressive risk factor modification is the firstline therapy for patients with symptomatic ICAD. Endovascular angioplasty with or without stenting is a possible therapeutic option for selected patients with symptomatic ICAD. Further studies are necessary to define appropriate patient selection and the best therapeutic approach for various subsets of patients.
The role of feelings of intimacy on perceptions of risk for a sexually transmitted disease and condom use in the sexual relationships of adolescent African–American females
Authors: Matson Pamela A , Chung Shang-en , Sander Petra , Millstein Susan G , Ellen Jonathan M
Published: June 2012

Objectives

A core construct targeted by behavioural interventions is the perception that one is at risk for acquiring a sexually transmitted disease (STD). The objective of this analysis was to examine the role of intimacy on perceptions of risk for an STD (PRSTD) and condom use within late adolescent females' main relationships.

Methods

A clinical sample of African–American women aged 14–19 years at enrolment were followed prospectively for 3 years. At each semiannual interview, participants reported their partner-specific PRSTD, feelings of intimacy, perceptions of partner's concurrency and condom use at last sex for each of their main sex partners.

Results

A total of 285 individuals reported 724 main relationships. Using generalised estimating equations, intimacy was negatively associated with risk perception, after adjusting for perceptions of partner concurrency (OR: 0.68; 95% CI 0.60 to 0.76). PRSTD was no longer associated with condom use after adjusting for intimacy (OR: 1.30; 95% CI 0.83 to 2.02.

Conclusions

Intimacy was found to be associated with risk perception and condom use within adolescent main relationships. Adolescents may not view their intimate partners as sources of infection. The success of individual-level STD prevention efforts, such as condom promotion, might be limited as condoms may be in conflict with adolescents' expectations about intimate relationships.
Laparoscopic ovariectomy in dogs using a single‐port multiple‐access device
Authors: Manassero M. , Leperlier D. , Vallefuoco R. , Viateau V.
Published: June 2012

The aim of this case series was to describe a novel technique of single‐incision laparoscopic ovariectomy in dogs using the SILS Port (Covidien), a single‐port multiple‐access device, in 40 client‐owned dogs. A single 3 cm incision was made caudal to the umbilicus and the SILS Port device was bluntly introduced. Three cannulae were inserted in the SILS Port through the access channels. In the first 20 cases, a transabdominal suspension suture was used to transfix the ovaries. In all cases, ovariectomy was performed using a standard straight non‐roticulated laparoscopic grasper and a vessel sealer/divider device. Mean (sd) duration of the ovarian resection was 25.1 (6.1) minutes (range 16 to 39 minutes). In five dogs (with transabdominal suspension suture), minor bleeding in the mesovarium or in the spleen was observed. Since the SILS Port allows simultaneous use of two instruments and a telescope through a single incision, the suspension suture is not mandatory. The lack of a transabdominal suspension suture increased collision between instruments and the telescope, but triangulation capabilities remained sufficient to achieve visualisation, sufficient manoeuvrability and safe vessel sealer/divider device application. The time to perform ovarian resection remained unaltered with or without suspension suture and regardless of the fat score of the ovarian ligament. Complications were less frequent without a suspension suture.
Pig‐shed air polluted by α‐haemolytic cocci and ammonia causes subclinical disease and production losses
Authors: Murphy T. , Cargill C. , Rutley D. , Stott P.
Published: June 2012

There is mounting evidence that bacteria originating from pigs degrade the environment of the pig shed and adversely affect the health of the animals and the pig‐shed workers. α‐haemolytic cocci (AHC) occur in pig‐shed environments, but are regarded as commensals. Ammonia is also a component of the pig‐shed environment, and is known to damage upper respiratory tract epithelia. The aim of this study was to determine whether polluted air in pig sheds adversely affected performance indicators in pigs. Modelling revealed a direct effect of AHC on voluntary feed intake and hence AHC are not commensal. No direct effect of ammonia on the pigs was detected, but the combination of AHC and ammonia stimulated the immune system in a progressive manner, and there were direct effects of immune stimulation on food intake and growth resulting in poorer feed‐conversion efficiency, even though the effects remained subclinical. The authors conclude that exposure of the respiratory epithelia of pigs to viable AHC in the presence of ammonia redirects nutrients away from production and towards the immune system, explaining the impact of poor pig‐shed hygiene on production parameters.
Serum gastrin concentrations in dogs with liver disorders
Authors: Mazaki‐Tovi M. , Segev G. , Yas‐Natan E. , Lavy E.
Published: June 2012

Dogs with liver disorders often display gastrointestinal signs that may be triggered by ulceration. The liver is important for inactivation of some forms of gastrin. Therefore, hypergastrinaemia has been implicated in the pathogenesis of gastrointestinal ulcerations related to liver dysfunction. The aim of this study was to determine serum gastrin concentrations in dogs with liver disease. Fasted blood samples were collected from 15 dogs with newly diagnosed liver disease and 18 healthy dogs. Gastrin concentrations were significantly lower in dogs with congenital portosystemic shunt compared with healthy dogs (P=0.003). No significant difference (P=0.6) in gastrin concentration was revealed between dogs with hepatocellular disease and healthy dogs. Serum gastrin concentrations were not significantly associated with the occurrence of vomiting, anorexia, diarrhoea, or melaena in dogs with liver disorders. These findings did not provide support for the role of hypergastrinaemia in the development of gastrointestinal signs associated with liver disease in dogs. Decreased serum concentrations of gastrin in a dog with liver disease may suggest the presence of portosystemic shunt. Further investigation is warranted to determine the importance of hyopogastrinaemia in congenital postosystemic shunts in dogs and to evaluate potential alterations in serum gastrin concentrations in specific hepatocellular diseases.
THE TDGL EQUATION FOR CAR-FOLLOWING MODEL WITH CONSIDERATION OF THE TRAFFIC INTERRUPTION PROBABILITY
Authors: GE HONG-XIA , ZHANG YI-QIANG , KUANG HUA , LO SIU-MING
Published: June 2012

A car-following model which involves the effects of traffic interruption probability is further investigated. The stability condition of the model is obtained through the linear stability analysis. The reductive perturbation method is taken to derive the time-dependent Ginzburg–Landau (TDGL) equation to describe the traffic flow near the critical point. Moreover, the coexisting curve and the spinodal line are obtained by the first and second derivatives of the thermodynamic potential, respectively. The analytical results show that considering the interruption effects could further stabilize traffic flow.
CONGRUENCE FD-MAXIMAL VARIETIES OF ALGEBRAS
Authors: GILLIBERT PIERRE , PLOŠČICA MIROSLAV
Published: June 2012

We study the class of finite lattices that are isomorphic to the congruence lattices of algebras from a given finitely generated congruence-distributive variety. If this class is as large as allowed by an obvious necessary condition, the variety is called congruence FD-maximal. The main results of this paper characterize some special congruence FD-maximal varieties.
Therapeutic administration of IL-11 exhibits the postconditioning effects against ischemia-reperfusion injury via STAT3 in the heart
Authors: Obana Masanori , Miyamoto Kaori , Murasawa Shiho , Iwakura Tomohiko , Hayama Akiko , Yamashita Tomomi , Shiragaki Momoko , Kumagai Shohei , Miyawaki Akimitsu , Takewaki Kana , Matsumiya Goro , Maeda Makiko , Yoshiyama Minoru , Nakayama Hiroyuki , Fujio Yasushi
Published: June 2012

Activation of cardiac STAT3 by IL-6 cytokine family contributes to cardioprotection. Previously, we demonstrated that IL-11, an IL-6 cytokine family, has the therapeutic potential to prevent adverse cardiac remodeling after myocardial infarction; however, it remains to be elucidated whether IL-11 exhibits postconditioning effects. To address the possibility that IL-11 treatment improves clinical outcome of recanalization therapy against acute myocardial infarction, we examined its postconditioning effects on ischemia/reperfusion (I/R) injury. C57BL/6 mice were exposed to ischemia (30 min) and reperfusion (24 h), and IL-11 was intravenously administered at the start of reperfusion. I/R injury mediated the activation of STAT3, which was enhanced by IL-11 administration. IL-11 treatment reduced I/R injury, analyzed by triphenyl tetrazolium chloride staining [PBS, 46.7 ± 14.4%; IL-11 (20 μg/kg), 28.6 ± 7.5% in the ratio of infarct to risk area]. Moreover, echocardiographic and hemodynamic analyses clarified that IL-11 treatment preserved cardiac function after I/R. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining revealed that IL-11 reduced the frequency of apoptotic cardiomyocytes after I/R. Interestingly, IL-11 reduced superoxide production assessed by in situ dihydroethidium fluorescence analysis, accompanied by the increased expression of metallothionein 1 and 2, reactive oxygen species (ROS) scavengers. Importantly, with the use of cardiac-specific STAT3 conditional knockout (STAT3 CKO) mice, it was revealed that cardiac-specific ablation of STAT3 abrogated IL-11-mediated attenuation of I/R injury. Finally, IL-11 failed to suppress the ROS production after I/R in STAT3 CKO mice. IL-11 administration exhibits the postconditioning effects through cardiac STAT3 activation, suggesting that IL-11 has the clinical therapeutic potential to prevent I/R injury in heart.
Development of dilated cardiomyopathy inBmal1-deficient mice
Authors: Lefta Mellani , Campbell Kenneth S. , Feng Han-Zhong , Jin Jian-Ping , Esser Karyn A.
Published: June 2012

Circadian rhythms are approximate 24-h oscillations in physiology and behavior. Circadian rhythm disruption has been associated with increased incidence of hypertension, coronary artery disease, dyslipidemia, and other cardiovascular pathologies in both humans and animal models. Mice lacking the core circadian clock gene, brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein ( Bmal1), are behaviorally arrhythmic, die prematurely, and display a wide range of organ pathologies. However, data are lacking on the role of Bmal1 on the structural and functional integrity of cardiac muscle. In the present study, we demonstrate that Bmal1−/−mice develop dilated cardiomyopathy with age, characterized by thinning of the myocardial walls, dilation of the left ventricle, and decreased cardiac performance. Shortly after birth the Bmal1−/−mice exhibit a transient increase in myocardial weight, followed by regression and later onset of dilation and failure. Ex vivo working heart preparations revealed systolic ventricular dysfunction at the onset of dilation and failure, preceded by downregulation of both myosin heavy chain isoform mRNAs. We observed structural disorganization at the level of the sarcomere with a shift in titin isoform composition toward the stiffer N2B isoform. However, passive tension generation in single cardiomyocytes was not increased. Collectively, these findings suggest that the loss of the circadian clock gene, Bmal1, gives rise to the development of an age-associated dilated cardiomyopathy, which is associated with shifts in titin isoform composition, altered myosin heavy chain gene expression, and disruption of sarcomere structure.
Midkine acts as proangiogenic cytokine in hypoxia-induced angiogenesis
Authors: Weckbach Ludwig T. , Groesser Leopold , Borgolte Julia , Pagel Judith-Irina , Pogoda Frank , Schymeinsky Jürgen , Müller-Höcker Josef , Shakibaei Mehdi , Muramatsu Takashi , Deindl Elisabeth , Walzog Barbara
Published: June 2012

The cytokine midkine (MK) promotes tumor growth mainly by inducing angiogenesis. Here, we identified the source of MK in the vascular system under hypoxic conditions and demonstrated the relevance of MK during ischemia of normal tissue. Hypoxia increased MK protein expression in human polymorphonuclear neutrophils (PMN), monocytes, and human umbilical vein endothelial cells (HUVEC) compared with normoxia. Immunoelectron microscopy showed elevated cell surface expression of MK in PMN and monocytes during hypoxia. However, only HUVEC released significant amounts of soluble MK during hypoxia compared with normoxia (301 ± 81 pg/ml vs. 158 ± 45 pg/ml; P < 0.05). Exogenous MK induced neovascularization in a chorioallantoic membrane (CAM) assay compared with negative control as measured by counting the number of branching points per visual field (1,074 ± 54 vs. 211 ± 70; P < 0.05). In a hind limb ischemia model, the angiogenic response was almost completely absent in MK-deficient mice, whereas control animals showed a profound angiogenic response measured as proliferating endothelial cells per visual field (45 ± 30 vs. 169 ± 34; P < 0.01). These unanticipated results identified endothelial cells as the source of soluble MK in the vascular system during hypoxia and defined MK as a pivotal player of angiogenesis during ischemia in nonmalignant tissue.
Inflection points in sepsis biology: from local defense to systemic organ injury
Authors: Seeley Eric J. , Matthay Michael A. , Wolters Paul J.
Published: June 2012

Sepsis and septic shock lead to considerable morbidity and mortality in developed and developing countries. Despite advances in understanding the innate immune events that lead to septic shock, molecular therapies based on these advances have failed to improve sepsis mortality. The clinical failure of laboratory-derived therapies may be, in part, due to the pleiotropic consequences of the acute inflammatory response, which is the focus of this review. A brisk response to infecting organism is essential for pathogen containment and eradication. However, systemic spread of inflammation beyond a single focus leads to organ injury and higher mortality. The primary goal of this article is to discuss recent animal- and human-based scientific advances in understanding the host response to infection and to highlight how these defense mechanisms can be locally beneficial but systemically detrimental. There are other factors that determine the severity of sepsis that are beyond the scope of this review, including the virulence of the pathogen and regulation by Toll-like receptors. Specifically, this review focuses on how the effector mechanisms of platelets, mast cells, neutrophil extracellular traps (NETs), and the endothelium participate in combating local infections yet can induce organ injury during systemic infection.
Hypermethylation-mediated silencing of p14ARF in fibroblasts from idiopathic pulmonary fibrosis
Authors: Cisneros José , Hagood James , Checa Marco , Ortiz-Quintero Blanca , Negreros Miguel , Herrera Iliana , Ramos Carlos , Pardo Annie , Selman Moisés
Published: June 2012

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. A conspicuous feature is the formation and persistence of fibroblastic/myofibroblastic foci throughout the lung parenchyma. Mechanisms remain unknown, but data indicate that fibroblasts acquire an antiapoptotic phenotype. We hypothesized that transcriptional silencing of proapoptotic genes may be implicated, and accordingly we evaluated the epigenetic regulation of p14ARF. The expression of p14ARF was analyzed by RT-PCR in IPF ( n = 8) and normal derived fibroblasts ( n = 4) before and after treatment with 5-aza-2′-deoxycytidine (5-aza) and trichostatin A (TSA). p14ARF gene promoter methylation was determined by methylation-specific PCR (MS-PCR) and by DNA digestion with endonuclease McrBc, which cleaves 50% of methylated CpG. Apoptosis was evaluated by Annexin-V and nuclear staining. p14ARF expression was significantly decreased in four of the eight IPF fibroblasts lines, which was restored after 5-aza treatment. No changes were found with TSA. MS-PCR of bisulfite-treated genomic DNA showed a correlation between the reduced expression of p14ARF and the presence of hypermethylated promoter. No amplification was observed in the DNA treated with the McrBc enzyme, corroborating promoter hypermethylation. p14ARF-hypermethylated IPF fibroblasts were significantly more resistant to staurosporine-and S-nitrosoglutathione-induced apoptosis compared with normal and nonmethylated IPF fibroblasts ( P < 0.01) and showed reduced levels of p53. Resistance to apoptosis was provoked in fibroblasts when p14ARF expression was inhibited by siRNA ( P < 0.05). These findings demonstrate that many IPF fibroblasts have reduced expression of the proapoptotic p14ARF attributable to promoter hypermethylation and indicate that epigenetic mechanisms may underlie their resistance to apoptosis.
8-OH-DPAT abolishes the pulmonary C-fiber-mediated apneic response to fentanyl largely via acting on 5HT1Areceptors in the nucleus tractus solitarius
Authors: Zhuang Jianguo , Zhang Zhenxiong , Zhang Cancan , Xu Fadi
Published: June 2012

Intravenous bolus injection of morphine causes a vagal-mediated brief apnea (∼3 s), while continuous injection, via action upon central μ-opioid receptor (MOR), arrests ventilation (>20 s) that is eliminated by stimulating central 5-hydroxytryptamine 1A receptors (5HT1ARs). Bronchopulmonary C-fibers (PCFs) are essential for triggering a brief apnea, and their afferents terminate at the caudomedial region of the nucleus tractus solitarius (mNTS) that densely expresses 5HT1ARs. Thus we asked whether the vagal-mediated apneic response to MOR agonists was PCF dependent, and if so, whether this apnea was abolished by systemic administration of 8-hydroxy-2-(di- n-propylamino)tetral (8-OH-DPAT) largely through action upon mNTS 5HT1ARs. Right atrial bolus injection of fentanyl (5.0 μg/kg, a MOR agonist) was performed in the anesthetized and spontaneously breathing rats before and after: 1) selective blockade of PCFs' conduction and subsequent bivagotomy; 2) intravenous administration of 5HT1AR agonist 8-OH-DPAT; 3) intra-mNTS injection of 8-OH-DPAT; and 4) intra-mNTS injection of 5HT1AR antagonist WAY-100635 followed by 8-OH-DPAT (iv). We found the following: First, fentanyl evoked an immediate apnea (2.5 ± 0.4 s, ∼6-fold longer than the baseline expiratory duration, TE), which was abolished by either blocking PCFs' conduction or bivagotomy. Second, this apnea was prevented by systemic 8-OH-DPAT challenge. Third, intra-mNTS injection of 8-OH-DPAT greatly attenuated the apnea by 64%. Finally, intra-mNTS microinjection of WAY-100635 significantly attenuated (58%) the apneic blockade by 8-OH-DPAT (iv). We conclude that the vagal-mediated apneic response to MOR activation depends on PCFs, which is fully antagonized by systemic 8-OH-DPAT challenge largely via acting on mNTS 5HT1ARs.
Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility
Authors: Sung Hui-Jin , Ok Seong-Ho , Sohn Jin-Young , Son Yong Hyeok , Kim Jun Kyu , Lee Soo Hee , Han Jeong Yeol , Lim Dong Hoon , Shin Il-Woo , Lee Heon-Keun , Chung Young-Kyun , Choi Mun-Jeoung , Sohn Ju-Tae
Published: June 2012

Aminoamide local anesthetics induce vasoconstrictionin vivoandin vitro. The goals of thisin vitrostudy were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine) were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50) of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50) of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2=0.9563;P<0.001). The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.
PPARγas a Potential Target to Treat Airway Mucus Hypersecretion in Chronic Airway Inflammatory Diseases
Authors: Shen Yongchun , Chen Lei , Wang Tao , Wen Fuqiang
Published: June 2012

Airway mucus hypersecretion (AMH) is a key pathophysiological feature of chronic airway inflammatory diseases such as bronchial asthma, cystic fibrosis, and chronic obstructive pulmonary disease. AMH contributes to the pathogenesis of chronic airway inflammatory diseases, and it is associated with reduced lung function and high rates of hospitalization and mortality. It has been suggested that AMH should be a target in the treatment of chronic airway inflammatory diseases. Recent evidence suggests that a key regulator of airway inflammation, hyperresponsiveness, and remodeling is peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcription factor that regulates adipocyte differentiation and lipid metabolism. PPARγis expressed in structural, immune, and inflammatory cells in the lung. PPARγis involved in mucin production, and PPARγagonists can inhibit mucin synthesis bothin vitroandin vivo. These findings suggest that PPARγis a novel target in the treatment of AMH and that further work on this transcription factor may lead to new therapies for chronic airway inflammatory diseases.
Idiopathic Radiation Recall Dermatitis Developing Nine Months after Cessation of Cisplatin Therapy in Treatment of Squamous Cell Carcinoma of the Tonsil
Authors: Melnyk Stephen M. , More Kenneth F. , Miles Edward F.
Published: June 2012

To report on a suspected case of idiopathic radiation recall dermatitis in an individual nine months after radiation and chemotherapy treatment of squamous cell carcinoma of the right tonsil. Radiation recall dermatitis is the development of a reaction in a previously irradiated area of skin after the administration of an aggravating medication. A review of the literature revealed several cases of radiation recall dermatitis that occur following radiation therapy and the institution of chemotherapy. Other medications have also been implicated in radiation recall dermatitis; however, this patient has not started any new medications since completion of his combined therapy. The patient developed this skin reaction in a distribution pattern identical to the area that received the highest radiation dose suggesting a possible link between radiation recall dermatitis and radiation dose. Radiation recall dermatitis is a reaction that is typically seen shortly after the reinstitution of chemotherapy during radiation therapy. This case illustrates that other medical etiologies are possible and suggests a relationship between radiation recall dermatitis and the total radiation dose an area receives.
Ovarian Pregnancy following Intracytoplasmic Sperm Injection and Embryo Transfer: A Case Report
Authors: Ramachandran Amar , Sharma Swati , Pratap Kumar , Rajesh Bhakta , Akhila Vasudeva , Ramayapally Akhila , Valiathan Manna
Published: June 2012

Ovarian pregnancy is a rare form of ectopic pregnancy following ICSI-ET, and the diagnosis depends on the physicians suspicion and experience. Preservation of ovarian tissue during surgery is of utmost importance to preserve fertility. We present a case of ovarian pregnancy who had a successful treatment preserving the ovary.
Role of Vibrational Spectroscopy in Stem Cell Research
Authors: Aksoy Ceren , Severcan Feride
Published: June 2012

Recent researches have mainly displayed the significant role of stem cells in tissue renewal and homeostasis with their unique capacity to develop different cell types. These findings have clarified the importance of stem cells to improve the effectiveness of any cell therapy for regenerative medicine. Identification of purity and differentiation stages of stem cells are the greatest challenges of stem cell biology and regenerative medicine. The existing methods to carefully monitor and characterize the stem cells have some unwanted effects on the properties of stem cells, and these methods also do not provide real-time information about cellular conditions. These challenges enforce the usage of nondestructive, rapid, sensitive, high quality, label-free, cheep, and innovative chemical monitoring methods. In this context, vibrational spectroscopy provides promissing alternative to get new information into the field of stem cell biology for chemical analysis, quantification, and imaging of stem cells. Raman and infrared spectroscopy and imaging can be used as a new complimentary spectroscopic approaches to gain new insight into stem cell reseaches for future therapeutic and regenerative medicines. In this paper, recent developments in applications of vibrational spectroscopy techniques for stem cell characterization and identification are presented.
Bone: Incretin Hormones Perceiver or Receiver?
Authors: Dicembrini Ilaria , Mannucci Edoardo , Rotella Carlo Maria
Published: June 2012

Novel incretin-based drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), have been last introduced in the pharmacological treatment of type 2 diabetes. In the last few years, the interest on the relationship of gut hormones with bone metabolism in diabetes has been increasing. The aim of present paper is to examinein vitroandin vivoevidence on the connections between incretin hormones and bone metabolism. We also discuss results of clinical trials and metaanalysis, explore the effects of incretin drugsin vitroon osteogenic cells and osteoclasts, and speculate on the possibility of different effects of GLP-1 RA and DPP-4i on the risk of bone fractures risk in humans. Although existing preliminary evidence suggests a protective effect on the bone, at least for DPP-4i, further controlled, long-term studies with measurement of bone markers, bone density, and clinical fractures rates are needed to substantiate and confirm those findings.