bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering Recombinant Orsay Virus Directly in the Metazoan Host Caenorhabditis elegans
Authors: Jiang Hongbing , Franz Carl J. , Wang David
Published: July 2014

The recent identification of Orsay virus, the first virus that is capable of naturally infecting
Caenorhabditis elegans
, provides a unique opportunity to explore host-virus interaction studies in this invaluable model organism. A key feature of this system is the robust genetic tractability of the host,
C. elegans
, which would ideally be complemented by the ability to genetically manipulate Orsay virus in parallel. To this end, we developed a plasmid-based reverse genetics system for Orsay virus by creating transgenic
C. elegans
strains harboring Orsay virus cDNAs. Both wild-type and mutant Orsay viruses, including a FLAG epitope-tagged recombinant Orsay virus, were generated by use of the reverse genetics system. This is the first plasmid-based virus reverse genetics system in the metazoan
C. elegans
. The Orsay virus reverse genetics we established will serve as a fundamental tool in host-virus interaction studies in the model organism
C. elegans
.

IMPORTANCE
To date, Orsay virus is the first and the only identified virus capable of naturally infecting
Caenorhabditis elegans
.
C. elegans
is a simple multicellular model organism that mimics many fundamental features of human biology and has been used to define many biological properties conserved through evolution. Thus, the Orsay virus-
C. elegans
infection system provides a unique opportunity to study host-virus interactions. In order to take maximal advantage of this system, the ability to genetically engineer mutant forms of Orsay virus would be highly desirable. Most efforts to engineer viruses have been done with cultured cells. Here we describe the creation of mutant viruses directly in the multicellular organism
C. elegans
without the use of cell culture. We engineered a virus expressing a genetically tagged protein that could be detected in
C. elegans
. This provides proof of concept for modifying Orsay virus, which will greatly facilitate studies in this experimental system.
Cross-sectional association between cigarette smoking and abdominal obesity among Austrian bank employees
Authors: de Oliveira Fontes Gasperin Lizia , Neuberger Manfred , Tichy Alexander , Moshammer Hans
Published: July 2014

Objectives

There is increasing evidence that smoking is associated with abdominal obesity and other risk factors for the metabolic syndrome. The aim of this study is to investigate these associations in a sample of healthy Austrian adults.

Setting and participants

Data of 986 employees of an Austrian company (405 men and 581 women; participation rate approximately 80%) obtained during their annual medical check-up at the workplace were analysed.

Primary and secondary outcome measures

Information on smoking status, education level, physical activity, diet, body weight, height, body mass index (BMI), waist circumference and biochemical parameters was obtained. The influence of smoking on health and anthropometric measures was investigated.

Results

No differences in total body fat and/or body fat distribution were found between non-smokers, smokers and former smokers; however, among daily smokers, the number of cigarettes smoked per day was significantly associated with higher body weight (p=0.001) and BMI (p=0.009). Male and female smokers had significantly higher white cell count than non-smokers and former smokers. Heavy smokers also had an unhealthier lipid profile (lower high-density lipoprotein cholesterol) and higher fasting glucose levels even after controlling for physical activity and calorie intake.

Conclusions

Contrary to the beliefs of many smokers, heavy smoking is associated with higher body weight and unfavourable metabolic changes.
Assessment of the quality of reporting in randomised controlled trials of acupuncture in the Korean literature using the CONSORT statement and STRICTA guidelines
Authors: Kim Kun Hyung , Kang Jung Won , Lee Myeong Soo , Lee Jae-Dong
Published: July 2014

Objectives

This study aims to assess the completeness of reporting of randomised controlled trials (RCTs) of acupuncture in the Korean literature.

Design

Systematic review.

Methods

We searched 12 Korean databases and 7 Korean journals to identify eligible RCTs of acupuncture published from 1996 to July 2011. We used the Consolidated Standards of Reporting Trials (CONSORT) checklist for parallel RCTs and the revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) to assess the quality of reporting in Korean RCTs. We compared the completeness of reporting of CONSORT and STRICTA items in RCTs published in two time periods (1996–2004 referred to as the early period and 2005–2011 referred to as the late period).

Results

We analysed 146 eligible RCTs using the CONSORT statement concerning RCTs of both needling and non-needling acupuncture and the STRICTA guidelines for 90 trials of needling acupuncture. Among the 103 RCTs in the late period, the proportion of RCTs that completely reported the CONSORT items of outcome definition (15.5%), sample size calculation (2.9%), randomisation (56%), allocation concealment (5.8%), implementation of allocation (11.7%), outcome assessor blinding (20.3%), flow of participants (25.2%), number of participants analysed (19.4%), ancillary analyses (0.0%), adverse events (24.3%), generalisability of findings (1.9%) and overall evidence (32.0%) remained small. Among the 61 RCTs of needling acupuncture in the late period, the STRICTA items of setting/context (24.6%) and practitioner background (27.9%) showed incomplete reporting. The completeness of reporting improved over time in several CONSORT and STRICTA items.

Conclusions

The completeness of reporting of Korean RCTs of acupuncture was suboptimal according to the CONSORT and revised STRICTA statements. Trial authors and journal editors should use the CONSORT statement and STRICTA guidelines for transparent reporting in Korean RCTs of acupuncture. The endorsement of the CONSORT and revised STRICTA statements in author instructions is also required.
Cost-effectiveness of ranibizumab and bevacizumab for age-related macular degeneration: 2-year findings from the IVAN randomised trial
Authors: Dakin Helen A , Wordsworth Sarah , Rogers Chris A , Abangma Giselle , Raftery James , Harding Simon P , Lotery Andrew J , Downes Susan M , Chakravarthy Usha , Reeves Barnaby C ,   on behalf of the IVAN Study Investigators
Published: July 2014

Objective

To assess the incremental cost and cost-effectiveness of continuous and discontinuous regimens of bevacizumab (Avastin) and ranibizumab (Lucentis) for neovascular age-related macular degeneration (nAMD) from a UK National Health Service (NHS) perspective.

Design

A within-trial cost-utility analysis with a 2-year time horizon, based on a multicentre factorial, non-inferiority randomised controlled trial.

Setting

23 hospital ophthalmology clinics.

Participants

610 patients aged ≥50 years with untreated nAMD in the study eye.

Interventions

0.5 mg ranibizumab or 1.25 mg bevacizumab given continuously (monthly) or discontinuously (as-needed) for 2 years.

Main outcome measures

Quality-adjusted life-years (QALYs).

Results

Total 2-year costs ranged from £3002/patient ($4700; 95% CI £2601 to £3403) for discontinuous bevacizumab to £18 590/patient ($29 106; 95% CI £18 258 to £18 922) for continuous ranibizumab. Ranibizumab was significantly more costly than bevacizumab for both continuous (+£14 989/patient ($23 468); 95% CI £14 522 to £15 456; p<0.001) and discontinuous treatment (+£8498 ($13 305); 95% CI £7700 to £9295; p<0.001), with negligible difference in QALYs. Continuous ranibizumab would only be cost-effective compared with continuous bevacizumab if the NHS were willing to pay £3.5 million ($5.5 million) per additional QALY gained. Patients receiving continuous bevacizumab accrued higher total costs (+£599 ($938); 95% CI £91 to £1107; p=0.021) than those receiving discontinuous bevacizumab, but also accrued non-significantly more QALYs (+0.020; 95% CI −0.032 to 0.071; p=0.452). Continuous bevacizumab therefore cost £30 220 ($47 316) per QALY gained versus discontinuous bevacizumab. However, bootstrapping demonstrated that if the NHS is willing to pay £20 000/QALY gained, there is a 37% chance that continuous bevacizumab is cost-effective versus discontinuous bevacizumab.

Conclusions

Ranibizumab is not cost-effective compared with bevacizumab, being substantially more costly and producing little or no QALY gain. Discontinuous bevacizumab is likely to be the most cost-effective of the four treatment strategies evaluated in this UK trial, although there is a 37% chance that continuous bevacizumab is cost-effective.

Trial registration number

ISRCTN92166560.
A point prevalence cross-sectional study of healthcare-associated urinary tract infections in six Australian hospitals
Authors: Gardner Anne , Mitchell Brett , Beckingham Wendy , Fasugba Oyebola
Published: July 2014

Objectives

Urinary tract infections (UTIs) account for over 30% of healthcare-associated infections. The aim of this study was to determine healthcare-associated UTI (HAUTI) and catheter-associated UTI (CAUTI) point prevalence in six Australian hospitals to inform a national point prevalence process and compare two internationally accepted HAUTI definitions. We also described the level and comprehensiveness of clinical record documentation, microbiology laboratory and coding data at identifying HAUTIs and CAUTIs.

Setting

Data were collected from three public and three private Australian hospitals over the first 6 months of 2013.

Participants

A total of 1109 patients were surveyed. Records of patients of all ages, hospitalised on the day of the point prevalence at the study sites, were eligible for inclusion. Outpatients, patients in adult mental health units, patients categorised as maintenance care type (ie, patients waiting to be transferred to a long-term care facility) and those in the emergency department during the duration of the survey were excluded.

Outcome measures

The primary outcome measures were the HAUTI and CAUTI point prevalence.

Results

Overall HAUTI and CAUTI prevalence was 1.4% (15/1109) and 0.9% (10/1109), respectively.Staphylococcus aureusandCandidaspecies were the most common pathogens. One-quarter (26.3%) of patients had a urinary catheter and fewer than half had appropriate documentation. Eight of the 15 patients ascertained to have a HAUTI based on clinical records (6 being CAUTI) were coded by the medical records department with an International Classification of Diseases (ICD)-10 code for UTI diagnosis. The Health Protection Agency Surveillance definition had a positive predictive value of 91.67% (CI 64.61 to 98.51) compared against the Centers for Disease Control and Prevention definition.

Conclusions

These study results provide a foundation for a national Australian point prevalence study and inform the development and implementation of targeted healthcare-associated infection surveillance more broadly.
Quality of randomised controlled trials in medical education reported between 2012 and 2013: a systematic review protocol
Authors: Tolsgaard Martin G , Ku Cheryl , Woods Nicole N , Kulasegaram Kulamakan Mahan , Brydges Ryan , Ringsted Charlotte
Published: July 2014

Introduction

Research in medical education has increased in volume over the past decades but concerns have been raised regarding the quality of trials conducted within this field. Randomised controlled trials (RCTs) involving educational interventions that are reported in biomedical journals have been criticised for their insufficient conceptual, theoretical framework. RCTs published in journals dedicated to medical education, on the other hand, have been questioned regarding their methodological rigour. The aim of this study is therefore to assess the quality of RCTs of educational interventions reported in 2012 and 2013 in journals dedicated to medical education compared to biomedical journals with respect to objective quality criteria.

Methods and analysis

RCTs published between 1 January 2012 and 31 December 2013 in English are included. The search strategy is developed with the help of experienced librarians to search online databases for key terms. All of the identified RCTs are screened based on their titles and abstracts individually by the authors and then compared in pairs to assess agreement. Data are extracted from the included RCTs by independently scoring each RCT using a data collection form. The data collection form consists of four steps. Step 1 includes confirmation of RCT eligibility; step 2 consists of the CONSORT checklist; step 3 consists of the Medical Education Research Study Quality Instrument framework; step 4 consists of a Medical Education Extension (MEdEx) to the CONSORT checklist. The MEdEx includes the following elements: Description of scientific background, explanation of rationale, quality of research questions and hypotheses, clarity in the description of the use of the intervention and control as well as interpretation of results.

Ethics and dissemination

This review is the first to systematically examine the quality of RCTs conducted in medical education. We plan to disseminate the results through publications and presentation at relevant conferences. Ethical approval is not sought for this review.
Prevention of surgical site infection in lower limb skin lesion excisions with single dose oral antibiotic prophylaxis: a prospective randomised placebo-controlled double-blind trial
Authors: Smith Samuel C , Heal Clare F , Buttner Petra G
Published: July 2014

Objectives

To determine the effectiveness of a single perioperative prophylactic 2 g dose of cephalexin in preventing surgical site infection (SSI) following excision of skin lesions from the lower limb.

Design

Prospective double-blinded placebo-controlled trial testing for difference in infection rates.

Setting

Primary care in regional North Queensland, Australia.

Participants

52 patients undergoing lower limb skin lesion excision.

Interventions

2 g dose of cephalexin 30–60 min before excision.

Main outcome measures

Incidence of SSI.

Results

Incidence of SSI was 12.5% (95% CI 2.7% to 32.4%) in the cephalexin group compared with 35.7% (95% CI 18.6% to 55.9%) in the placebo group (p=0.064). This represented an absolute reduction of 23.21% (95% CI −0.39% to 46.82%), relative reduction of 65.00% (95% CI −12.70% to 89.13%) and number-needed-to-treat of 4.3.

Conclusions

Administration of a single 2 g dose of cephalexin 30–60 min before skin lesion excision from the lower limb may produce a reduction in the incidence of infection; however, this study was underpowered to statistically determine this.

Trial registration number

ACTRN12611000595910.
Prevalence and correlates of sleep disturbance and depressive symptoms among Chinese adolescents: a cross-sectional survey study
Authors: Guo Lan , Deng Jianxiong , He Yuan , Deng Xueqing , Huang Jinghui , Huang Guoliang , Gao Xue , Lu Ciyong
Published: July 2014

Study objective

To investigate the prevalence and the correlates of sleep disturbance and depressive symptoms among Chinese adolescents and to examine the association between the two problems.

Design

Cross-sectional survey.

Participants

A total of 3186 school students in grades 7–12 were sampled from the schools in Guangdong. A stratified-cluster random-sampling strategy was used to select the schools.

Main outcome measures

A self-administered questionnaire was used. The Pittsburgh Sleep Quality index (PSQI) was used to assess the occurrence of sleep disturbance, and the Center for Epidemiology Scale for Depression (CES-D) was used to identify whether individuals had depressive symptoms.

Results

The mean PSQI global score was 8.7 (±2.4) points, and 39.6% of the total sample had sleep disturbance. The mean CES-D score of students was 15.2 (±9.4) points, and 6.4% of the students had depressive symptoms. Additionally, girls and older adolescents were more likely to suffer from sleep disturbance, and the students who had depressive symptoms were 2.47 (95% CI 1.61 to 3.79) times more likely to suffer from sleep disturbance. Factors that were correlated with sleep disturbance and depressive symptoms were having a poor relationship with teachers, feeling lonely, suicide ideation and having run away from home.

Conclusions

Sleep disturbance was determined to be more prevalent among Chinese adolescents with depressive symptoms. Sleep disturbance and depressive symptoms were associated with each other, while school factors, family factors and psychosocial adjustment were comprehensively correlated with both.
Characteristics of hospital-treated intentional drug overdose in Ireland and Northern Ireland
Authors: Griffin Eve , Corcoran Paul , Cassidy Linda , O'Carroll Amanda , Perry Ivan J , Bonner Brendan
Published: July 2014

Objectives

This study compared the profile of intentional drug overdoses (IDOs) presenting to emergency departments in Ireland and in the Western Trust Area of Northern Ireland between 2007 and 2012. Specifically the study aimed to compare characteristics of the patients involved, to explore the factors associated with repeated IDO and to report the prescription rates of common drug types in the population.

Methods

We utilised data from two comparable registries which monitor the incidence of hospital-treated self-harm, recording data from deliberate self-harm presentations involving an IDO to all hospital emergency departments for the period 1 January 2007 to 31 December 2012.

Results

Between 2007 and 2012 the registries recorded 56 494 self-harm presentations involving an IDO. The study showed that hospital-treated IDO was almost twice as common in Northern Ireland than in Ireland (278 vs 156/100 000, respectively).

Conclusions

Despite the overall difference in the rates of IDO, the profile of such presentations was remarkably similar in both countries. Minor tranquillisers were the drugs most commonly involved in IDOs. National campaigns are required to address the availability and misuse of minor tranquillisers, both prescribed and non-prescribed.
Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies
Authors: Ross J S , Wang K , Rand J V , Gay L , Presta M J , Sheehan C E , Ali S M , Elvin J A , Labrecque E , Hiemstra C , Buell J , Otto G A , Yelensky R , Lipson D , Morosini D , Chmielecki J , Miller V A , Stephens P J
Published: July 2014

Aims

Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice.

Methods

DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs).

Results

At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were inTP53(34%),NF1(14%),CDKN2A(14%),MEN1(14%),CTNNB1(10%) andATM(10%).APC,CCND2,CDK4,DAXX,DNMT3A,KDM5C,LRP1B,MSH2andRB1were each altered in two cases (7%) andEGFR,ERBB4,KRAS,MDM2,NRAS,PDGFRB,PIK3CA,PTENandPTCH1were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial.

Conclusions

Next-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer.
Clinical utility of selective molecular genotyping for diagnosis of partial hydatidiform mole; a retrospective study from a regional trophoblastic disease unit
Authors: Fisher Rosemary A , Tommasi Anna , Short Dee , Kaur Baljeet , Seckl Michael J , Sebire Neil J
Published: July 2014

Aims

Hydatidiform moles (HMs) are genetically abnormal conceptions, associated with increased risk of gestational trophoblastic neoplasia. Diagnosis is usually based on histopathological criteria but in a minority definitive histological diagnosis is not possible; in such cases molecular genotyping may be diagnostic. This study describes the clinical usefulness of such an approach.

Methods

Cases in which central histology review demonstrated abnormal villous morphological features insufficient for definite diagnosis of partial HM (PHM) (‘favour PHM’ or ‘PHM not excluded’) underwent molecular genotyping of villous and maternal tissue, using short tandem repeats, to determine ploidy and parental origin of the placental tissue.

Results

Of 251 cases with non-diagnostic morphological villous abnormalities, molecular investigation was not possible in 14 (6%; limited material or technical issues). Overall, 124 (49%) were triploid including 71/86 (85%) of those morphologically favouring PHM, and 53/165 (32%) of those favouring non-molar miscarriage. Of 85 cases of triploidy in whom sufficient material was available, 84 had an additional paternal contribution. Single cases of digynic triploidy, tetraploid PHM and two mosaic conceptions were also identified. Twenty-three non-molar diploid cases (21%) exhibited trisomy.

Conclusions

Molecular genotyping allows definitive diagnosis of PHM for cases in which specialist histopathology review remains equivocal. While this approach provides definite diagnosis it is considerably more expensive than a pragmatic management approach of human chorionic gonadotrophin surveillance in all such cases.
Tax evasion dynamics and nonequilibrium Zaklan model with heterogeneous agents on square lattice
Authors: Lima F. W. S.
Published: July 2014

In this paper, we use the version of the nonequilibrium Zaklan model via agent-based Monte-Carlo simulations to study the problem of the fluctuations of the tax evasion on a heterogeneous agents community of honest and tax evaders citizens. The time evolution of this system is performed by a nonequilibrium model known as majority-vote model, but with a different probability for each agent to disobey the majority vote of its neighbors.
A NEW APPROACH TO MODELING CONDITION-BASED MAINTENANCE FOR STOCHASTICALLY DETERIORATING SYSTEMS
Authors: AHMADI REZA
Published: July 2014

This paper develops the degradation and maintenance modeling technique for repairable systems subject to deterioration due to aging and damage caused by operating environment factors. This provides a relaxed and generalized approach to modeling condition-based maintenance. The approach can deal with both the maintenance scheduling problem and failures preventing the system functioning further. Controlled by a virtual age process and a general class of process called Piecewise-Stochastic (Damage) process (PSP), the proportional intensity model (PIM) is used to describe the system state. The state of the system is monitored at periodic times and maintenance actions are carried out in response to the system state revealed at inspection times. Assuming a threshold-type policy, the approach aims at minimizing the long-run average cost per unit time subject to maintenance parameters; the inspection interval and preventive replacement threshold. To this end, given some assumptions, expressions for the expected cycle length and expected cost per cycle emerging as solutions of the Fredholm integral equations are obtained. The solution technique has been presented for the case when the effect of operating environment is modeled as a Gamma process.
Nash Equilibria of Co-Operative Advertising Programs with Advertising Threshold Effects
Authors: Gou Qinglong , Zhang Juzhi , Zhang Juan , Liang Liang
Published: July 2014

As an important advertising phenomenon which has been proven by previous empirical marketing research, the advertising threshold effect implies that advertising has little effect on sales when advertising investment is beneath a certain level. In this paper, we focus on a cooperative advertising program, in which a manufacturer shares part of its retailer’s advertising cost, to illustrate the impact of the advertising threshold effect. Dividing the advertisement efforts into national and local advertising, we propose a new advertising response model which can describe the advertising threshold effect well. Based on the advertising response function, we derive the manufacturer’s and the retailer’s equilibrium advertising investments when they play a Nash game. From the analysis we find that there are four possible Nash equilibria when we take the advertising threshold effect into account. We derive the sufficient and necessary conditions under which each of the four possible equilibria is a Nash equilibrium, and explain these conditions with examples from practice. Another interesting result is that there are two different equilibria when certain conditions are satisfied.
Certain transformations for hypergeometric series in the p-adic setting
Authors: Barman Rupam , Saikia Neelam
Published: July 2014

In [The trace of Frobenius of elliptic curves and the p-adic gamma function, Pacific J. Math. 261(1) (2013) 219–236], McCarthy defined a function nGn[⋯] using the Teichmüller character of finite fields and quotients of the p-adic gamma function. This function extends hypergeometric functions over finite fields to the p-adic setting. In this paper, we give certain transformation formulas for the function nGn[⋯] which are not implied from the analogous hypergeometric functions over finite fields.
Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase
Authors: Cozzoli Anna , Liantonio Antonella , Conte Elena , Cannone Maria , Massari Ada Maria , Giustino Arcangela , Scaramuzzi Antonia , Pierno Sabata , Mantuano Paola , Capogrosso Roberta Francesca , Camerino Giulia Maria , De Luca Annamaria
Published: July 2014

Angiotensin II (ANG II) plays a role in muscle wasting and remodeling; however, little evidence shows its direct effects on specific muscle functions. We presently investigated the acute in vitro effects of ANG II on resting ionic conductance and calcium homeostasis of mouse extensor digitorum longus (EDL) muscle fibers, based on previous findings that in vivo inhibition of ANG II counteracts the impairment of macroscopic ClC-1 chloride channel conductance (gCl) in the mdx mouse model of muscular dystrophy. By means of intracellular microelectrode recordings we found that ANG II reduced gCl in the nanomolar range and in a concentration-dependent manner (EC50 = 0.06 μM) meanwhile increasing potassium conductance (gK). Both effects were inhibited by the ANG II receptors type 1 (AT1)-receptor antagonist losartan and the protein kinase C inhibitor chelerythrine; no antagonism was observed with the AT2 antagonist PD123,319. The scavenger of reactive oxygen species (ROS) N-acetyl cysteine and the NADPH-oxidase (NOX) inhibitor apocynin also antagonized ANG II effects on resting ionic conductances; the ANG II-dependent gK increase was blocked by iberiotoxin, an inhibitor of calcium-activated potassium channels. ANG II also lowered the threshold for myofiber and muscle contraction. Both ANG II and the AT1 agonist L162,313 increased the intracellular calcium transients, measured by fura-2, with a two-step pattern. These latter effects were not observed in the presence of losartan and of the phospholipase C inhibitor U73122 and the in absence of extracellular calcium, disclosing a Gq-mediated calcium entry mechanism. The data show for the first time that the AT1-mediated ANG II pathway, also involving NOX and ROS, directly modulates ion channels and calcium homeostasis in adult myofibers.
Active and passive heat stress similarly compromise tolerance to a simulated hemorrhagic challenge
Authors: Pearson J. , Lucas R. A. I. , Schlader Z. J. , Zhao J. , Gagnon D. , Crandall C. G.
Published: July 2014

Passive heat stress increases core and skin temperatures and reduces tolerance to simulated hemorrhage (lower body negative pressure; LBNP). We tested whether exercise-induced heat stress reduces LBNP tolerance to a greater extent relative to passive heat stress, when skin and core temperatures are similar. Eight participants (6 males, 32 ± 7 yr, 176 ± 8 cm, 77.0 ± 9.8 kg) underwent LBNP to presyncope on three separate and randomized occasions: 1) passive heat stress, 2) exercise in a hot environment (40°C) where skin temperature was moderate (36°C, active 36), and 3) exercise in a hot environment (40°C) where skin temperature was matched relative to that achieved during passive heat stress (∼38°C, active 38). LBNP tolerance was quantified using the cumulative stress index (CSI). Before LBNP, increases in core temperature from baseline were not different between trials (1.18 ± 0.20°C; P > 0.05). Also before LBNP, mean skin temperature was similar between passive heat stress (38.2 ± 0.5°C) and active 38 (38.2 ± 0.8°C; P = 0.90) trials, whereas it was reduced in the active 36 trial (36.6 ± 0.5°C; P ≤ 0.05 compared with passive heat stress and active 38). LBNP tolerance was not different between passive heat stress and active 38 trials (383 ± 223 and 322 ± 178 CSI, respectively; P = 0.12), but both were similarly reduced relative to active 36 (516 ± 147 CSI, both P ≤ 0.05). LBNP tolerance is not different between heat stresses induced either passively or by exercise in a hot environment when skin temperatures are similarly elevated. However, LBNP tolerance is influenced by the magnitude of the elevation in skin temperature following exercise induced heat stress.
Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin
Authors: Richards Jennifer P. , Yosten Gina L. C. , Kolar Grant R. , Jones Cory W. , Stephenson Alan H. , Ellsworth Mary L. , Sprague Randy S.
Published: July 2014

ATP release from erythrocytes in response to reduced oxygen (O2) tension stimulates local vasodilation, enabling these cells to direct perfusion to areas in skeletal muscle in need of O2. Erythrocytes of humans with type 2 diabetes do not release ATP in response to low O2. Both C-peptide and insulin individually inhibit low O2-induced ATP release from healthy human erythrocytes, yet when coadministered at physiological concentrations and ratios, no inhibition is seen. Here, we determined: that 1) erythrocytes of healthy humans and humans with type 2 diabetes possess a C-peptide receptor (GPR146), 2) the combination of C-peptide and insulin at physiological ratios rescues low O2-induced ATP release from erythrocytes of humans with type 2 diabetes, 3) residual C-peptide levels reported in humans with type 2 diabetes are not adequate to rescue low O2-induced ATP release in the presence of 1 nM insulin, and 4) the effects of C-peptide and insulin are neither altered by increased glucose levels nor explained by changes in erythrocyte deformability. These results suggest that the addition of C-peptide to the treatment regimen for type 2 diabetes could have beneficial effects on tissue oxygenation, which would help to ameliorate the concomitant peripheral vascular disease.
D1-like dopamine receptors downregulate Na+-K+-ATPase activity and increase cAMP production in the posterior gills of the blue crabCallinectes sapidus
Authors: Arnaldo Francis B. , Villar Van Anthony M. , Konkalmatt Prasad R. , Owens Shaun A. , Asico Laureano D. , Jones John E. , Yang Jian , Lovett Donald L. , Armando Ines , Jose Pedro A. , Concepcion Gisela P.
Published: July 2014

Dopamine-mediated regulation of Na+-K+-ATPase activity in the posterior gills of some crustaceans has been reported to be involved in osmoregulation. The dopamine receptors of invertebrates are classified into three groups based on their structure and pharmacology: D1- and D2-like receptors and a distinct invertebrate receptor subtype (INDR). We tested the hypothesis that a D1-like receptor is expressed in the blue crab Callinectes sapidus and regulates Na+-K+-ATPase activity. RT-PCR, using degenerate primers, showed the presence of D1βR mRNA in the posterior gill. The blue crab posterior gills showed positive immunostaining for a dopamine D5receptor (D5R or D1βR) antibody in the basolateral membrane and cytoplasm. Confocal microscopy showed colocalization of Na+-K+-ATPase and D1βR in the basolateral membrane. To determine the effect of D1-like receptor stimulation on Na+-K+-ATPase activity, intact crabs acclimated to low salinity for 6 days were given an intracardiac infusion of the D1-like receptor agonist fenoldopam, with or without the D1-like receptor antagonist SCH23390. Fenoldopam increased cAMP production twofold and decreased Na+-K+-ATPase activity by 50% in the posterior gills. This effect was blocked by coinfusion with SCH23390, which had no effect on Na+-K+-ATPase activity by itself. Fenoldopam minimally decreased D1βR protein expression (10%) but did not affect Na+-K+-ATPase α-subunit protein expression. This study shows the presence of functional D1βR in the posterior gills of euryhaline crabs chronically exposed to low salinity and highlights the evolutionarily conserved function of the dopamine receptors on sodium homeostasis.
eEOC-mediated modulation of endothelial autophagy, senescence, and EnMT in murine diabetic nephropathy
Authors: Patschan D. , Schwarze K. , Henze E. , Becker J. U. , Patschan S. , Müller G. A.
Published: July 2014

Diabetic nephropathy is the most frequent single cause of end-stage renal disease in our society. Microvascular damage is a key event in diabetes-associated organ malfunction. Early endothelial outgrowth cells (eEOCs) act protective in murine acute kidney injury. The aim of the present study was to analyze consequences of eEOC treatment of murine diabetic nephropathy with special attention on endothelial-to-mesenchymal transdifferentiation, autophagy, senescence, and apoptosis. Male C57/Bl6N mice (8–12 wk old) were treated with streptozotocin for 5 consecutive days. Animals were injected with untreated or bone morphogenetic protein (BMP)-5-pretreated syngeneic murine eEOCs on days 2 and 5 after the last streptozotocin administration. Four, eight, and twelve weeks later, animals were analyzed for renal function, proteinuria, interstitial fibrosis, endothelial-to-mesenchymal transition, endothelial autophagy, and senescence. In addition, cultured mature murine endothelial cells were investigated for autophagy, senescence, and apoptosis in the presence of glycated collagen. Diabetes-associated renal dysfunction (4 and 8 wk) and proteinuria (8 wk) were partly preserved by systemic cell treatment. At 8 wk, antiproteinuric effects were even more pronounced after the injection of BMP-5-pretreated cells. The latter also decreased mesenchymal transdifferentiation of the endothelium. At 8 wk, intrarenal endothelial autophagy (BMP-5-treated cells) and senescence (native and BMP-5-treated cells) were reduced. Autophagy and senescence in/of cultured mature endothelial cells were dramatically reduced by eEOC supernatant (native and BMP-5). Endothelial apoptosis decreased after incubation with eEOC medium (native and BMP-5). eEOCs act protective in diabetic nephropathy, and such effects are significantly stimulated by BMP-5. The cells modulate endothelial senescence, autophagy, and apoptosis in a protective manner. Thus, the renal endothelium could serve as a therapeutic target in diabetes-associated kidney dysfunction.
CXCR4 antagonism as a therapeutic approach to prevent acute kidney injury
Authors: Zuk A. , Gershenovich M. , Ivanova Y. , MacFarland R. T. , Fricker S. P. , Ledbetter S.
Published: July 2014

We examined whether antagonism of the CXCR4 receptor ameliorates the loss of renal function following ischemia-reperfusion. CXCR4 is ubiquitously expressed on leukocytes, known mediators of renal injury, and on bone marrow hematopoietic stem cells (HSCs). Plerixafor (AMD3100, Mozobil) is a small-molecule CXCR4 antagonist that mobilizes HSCs into the peripheral blood and also modulates the immune response in in vivo rodent models of asthma and rheumatoid arthritis. Treatment with plerixafor before and after ischemic clamping ameliorated kidney injury in a rat model of bilateral renal ischemia-reperfusion. Serum creatinine and blood urea nitrogen were significantly reduced 24 h after reperfusion, as were tissue injury and cell death. Plerixafor prevented the renal increase in the proinflammatory chemokines CXCL1 and CXCL5 and the cytokine IL-6. Flow cytometry of kidney homogenates confirmed the presence of significantly fewer leukocytes with plerixafor treatment; additionally, myeloperoxidase activity was reduced. AMD3465, a monocyclam analog of plerixafor, was similarly renoprotective. Four weeks postreperfusion, long-term effects included diminished fibrosis, inflammation, and ongoing renal injury. The mechanism by which CXCR4 inhibition ameliorates AKI is due to modulation of leukocyte infiltration and expression of proinflammatory chemokines/cytokines, rather than a HSC-mediated effect. The data suggest that CXCR4 antagonism with plerixafor may be a potential option to prevent AKI.
Resting state arousal and functional connectivity in autism spectrum disorder
Authors: Kleberg Johan Lundin
Published: July 2014

A recent study (Eilam-Stock T, Xu P, Cao M, Gu X, Van Dam NT, Anagnostou E, Kolevzon A, Soorya L, Park Y, Siller M, He Y, Hof PR, Fan J. Brain 137: 153–171, 2014) demonstrated that resting state electrodermal activity is correlated with different patterns of brain activity in subjects with autism spectrum disorder (ASD) than in typical controls. These results are considered in light of theories of atypical arousal in ASD.
Caries Correlates Strongly with Salivary Levels of Matrix Metalloproteinase-8
Authors: Hedenbjörk-Lager Anders , Bjørndal Lars , Gustafsson Anders , Sorsa Timo , Tjäderhane Leo , Åkerman Sigvard , Ericson Dan
Published: July 2014

The caries process in dentin involves the degradation of both mineral and organic matrix. The demineralization has been demonstrated to be caused by bacterial acids. However, the collagen degradation is considered to be initiated by endogenous proteolytic enzymes, mainly collagenolytic matrix metalloproteinases (MMPs). This paper aims to relate salivary MMP-8 (or salivary collagenase-2) and tissue inhibitor of MMP (TIMP-1) levels to manifest caries in a large number of subjects. A random sample of 451 adults (aged 18-87 years) living in the south of Sweden was included in this study. Standard clinical examinations were performed, and stimulated saliva was collected and analyzed for concentrations of MMP-8, TIMP-1 and total protein, using an immunofluorometric assay, an enzyme-linked immunosorbent assay and the Bradford assay, respectively. Salivary numbers of mutans streptococci and lactobacilli were determined using a chair-side kit. Subjects with manifest caries lesions presented with elevated levels of MMP-8 (p < 0.001) as well as total protein, MMP-8/TIMP-1 ratio, bleeding on probing and plaque index (p = 0.05) compared with subjects without manifest caries. Multiple linear regression analysis with caries as the dependent variable revealed MMP-8 as the only significant explanatory variable (p < 0.001). TIMP-1 was not significant in any case. Using MMP-8 as the dependent variable revealed total protein concentration, caries lesions (p ≤ 0.001) and salivary secretion rate (p = 0.05) as explanatory variables. In conclusion, our data reveal that subjects with manifest caries lesions have elevated levels of salivary MMP-8 relative to subjects with no caries lesions. © 2014 S. Karger AG, Basel
Increased Levels of Chitotriosidase and YKL-40 in Cerebrospinal Fluid from Patients with Alzheimer's Disease
Authors: Rosén Christoffer , Andersson Carl-Henrik , Andreasson Ulf , Molinuevo José L. , Bjerke Maria , Rami Lorena , Lladó Albert , Blennow Kaj , Zetterberg Henrik
Published: July 2014

Background: The cerebrospinal fluid (CSF) biomarkers total tau, abnormally phosphorylated tau and amyloid β 1-42 are strongly associated with Alzheimer's disease (AD). Apart from the pathologic hallmarks that these biomarkers represent, other processes such as inflammation and microglial activation are present in the brains of patients with AD. New biomarkers related to these processes could be valuable for the diagnosis and follow-up of AD patients and for the evaluation of inflammation-related pathologies. Aim: The aim of this study was to evaluate the association of inflammatory CSF biomarkers with AD. Methods: Twenty-five AD patients and 25 controls who had a pathological and normal CSF profile of the core AD biomarkers, respectively, were included in this study. CSF levels of chitotriosidase, YKL-40 (also known as chitinase-3-like protein 1) and monocyte chemoattractant protein-1 (MCP-1) were quantified and the levels compared between the groups. Results: AD patients had increased CSF levels of chitotriosidase and YKL-40 (both approximately twice higher than in controls), while the levels of MCP-1 were similar in the AD and control groups. Conclusion: The results indicate that chitotriosidase and YKL-40 may be helpful for the evaluation of cerebral inflammatory activity in AD patients.
Fetal Myocardial Wall Area: Constructing a Reference Range by Means of Spatiotemporal Image Correlation in the Rendering Mode
Authors: Barros Fernanda Silveira Bello , Moron Antonio Fernandes , Rolo Liliam Cristine , Rocha Luciane Alves , Martins Wellington P. , Tonni Gabriele , Nardozza Luciano Marcondes Machado , Araujo Júnior Edward
Published: July 2014

Objective: To establish the reference range of the myocardial wall area in the fetus using three-dimensional ultrasound in the rendering mode. Methods: A prospective, cross-sectional study including 371 singleton, uncomplicated pregnancies at 20 weeks 0 day to 33 weeks 6 days of gestation was carried out. Cardiac volumes were obtained using spatiotemporal image correlation (STIC) at the level of the four-chamber view. The end-diastolic myocardial area of the both ventricles was measured manually. The intraclass correlation coefficient (ICC) was used to assess intra- and interobserver concordance. Results: The mean myocardial area of the fetal right ventricular (RV) wall ranged from 0.86 ± 0.23 cm2 at 20 weeks 0 day to 2.75 ± 0.69 cm2 at 33 weeks 6 days of gestation. The mean myocardial area of the fetal left ventricular (LV) wall ranged from 0.82 ± 0.20 cm2 at 20 weeks 0 day to 2.49 ± 0.59 cm2 at 33 weeks 6 days of gestation. In addition, intra- and interobserver concordance for the myocardial area of the RV and LV walls was good, with ICC values of 0.94, 0.95, 0.85, and 0.93, respectively. Conclusions: The reference range for the myocardial area of the RV and LV walls was determined by cardio-STIC in the rendering mode at 20 weeks 0 day to 33 weeks 6 days of gestation, with good concordance between values.
β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo
Authors: Eriksen Morten , Ilebekk Arnfinn , Cataliotti Alessandro , Carlson Cathrine Rein , Lyberg Torstein , Aspelin Trude
Published: July 2014

Bradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.
Research Ethics Committees in the Field of Health-Related Human Research — A European Perspective and the Case of Austria
Authors: Stühlinger Verena , Hackl Michael
Published: July 2014

Human subject abuse and patient harm through medical research have led to the establishment of Institutional Review Boards (irbs or Research Ethics Committees (recs)), who independently scrutinise research protocols. In the field of trials with medicinal products as well as trials testing medical devices, an obligation for submission prior to realisation is granted within Europe through European directives. However, regulation of other fields of health-related research, e.g., psychological trials, public health and epidemiological studies or healthcare research is the responsibility of eu Member States; and European laws differ widely. The article gives an overview of European regulations in the field of rec review requirements, critically analyses Austrian legislation in this field and describes an institutional solution for legislative gaps in Austria — the Research Committee for Scientific and Ethical Questions (rcseq). Finally, important European initiatives for the future are pointed out.
Australian Marsh Beetles (Coleoptera: Scirtidae). 6. Genera Calvarium Pic, Papuacyphon Zwick, and Ypsiloncyphon Klausnitzer
Authors: ZWICK PETER
Published: July 2014

The genus Calvarium Pic, 1918 is for the first time recorded from Australia. Six new Australian species are named and described. Calvarium australiense n. sp. and C. superbum n. sp. from the Northern Territory are typical representatives of the genus. A new subgenus, Calvariellum n. subgen., is proposed for four species from NE Queensland which share general body structure with other Calvarium species but have different, less derived male genitalia: Calvarium (Calvariellum) bellendenker n. sp., C. (Calvariellum) cochlearifer n. sp., C. (Calvariellum) hamifer n. sp., and C. (Calvariellum) lancifer n. sp.        Papuacyphon darwini n. sp. is described from SW Australia. The genus was previously known only from Papua New Guinea.        Species Group 3 of the genus Ypsiloncyphon Klausnitzer, 2009 is first recorded from Australia. It is endemic to the Australasian region. The Australian species Y. angustus n. sp., Y. brevis n. sp., Y. katherinae n. sp., Y. longus n. sp., Y. pusillus n. sp., Y. velatus n. sp., and Y. virgulifer n. sp. are described, the New Guinean species Y. micans (Klausnitzer, 1973) (= Cyphon paramicans Klausnitzer, 1973, n. syn.), Y. mutilatus n. sp., Y. ruficollis n. sp., and Y. rugosus n. sp. are  described or redescribed from types, respectively. Three Australian species known only in the female sex are described under informal designations.
Synopsis of Oryssomini Gordon (Coleoptera: Coccinellidae)
from the Neotropical region with new species of Oryssomus Mulsant, Pseudoryssomus Gordon and Gordonoryssomus Almeida & Lima
Authors: ALMEIDA LÚCIA M. , SANTOS PAULA B.
Published: July 2014

Six new species of Oryssomus are described: O. calix sp. nov., O. guillermo sp. nov., O. guyanensis sp. nov. and O. rhombus sp. nov., from French Guiana; and O. paschoali sp. nov. and O. rogeri sp. nov., from Brazil. Four new species of Pseudoryssomus are described: P. brulei sp. nov., P. crucifer sp. nov., P. triangulus sp. nov., from French Guiana; and P. rufomarginatus sp. nov., from Trinidad and Tobago. Three new species of Gordonoryssomus are described: G. mirnae sp. nov., from Peru, G. everardoi sp. nov. and G. limeirai sp. nov., from Brazil. The new species are placed within the South American classification of Gordon (1974) and Almeida & Lima (1995). Keys to genera and species of Oryssomus, Pseudoryssomus and Gordonoryssomus are included. Distribution maps and a checklist of the known species of Oryssomini are provided.