bluuebunny/crossref_metadata_2025 huggingface dataset:
Where do they come from?
Authors: Zhang Heyou
Published: April 2015

Much work has been done to explore the origin and functions of the Chinese “Shi…De” construction, but there are still some problems left unsolved. Firstly, there is no consensus on what a syntactic category the “Shi…De” construction belongs to. Second, no agreement has been reached with regard to the functions ofDeandShiin the “Shi…De” construction. Third, the reason why Chinese chooses “Shi…De” to assume the function of focusing is not clear. Moreover, though previous studies have discussed the origin and the diachronic distribution of this construction, the mechanism for its generation or its genesis is left untouched. This paper discussed the Chinese “Shi…De” construction from a synchronic perspective. The findings include: (1) The Chinese “Shi…De” constructions are essentially assertive sentences which relate to the grammaticalization ofShi; (2)Deas an empty word is a particle at the phrase level and a functor together with aShiat the sentence level; (3) The “Shi…De” construction is endowed with its own semantic function; (4) The mechanism for forming Chinese cleft sentences is analogy.
Possessive / bahuvrīhi compounds in German
Authors: Koliopoulou Maria
Published: April 2015

This paper deals with structural properties of German possessive compounds. Based on a comparison with compounds in Modern Greek, I argue against a general approach based exclusively on semantic criteria. Instead I distinguish between exocentric and endocentric formations in German, on the basis of specific structural criteria. In particular, I propose that compounds like Dickkopf ‘pigheaded person’ — also called bahuvrīhi or exocentric formations — are to be analysed as endocentric, right-headed compounds with a metonymical meaning. Furthermore, I propose that structures like Vierfüßer ‘quadruped’ and heißblütig ‘warm-blooded/hot-tempered’ are the real bahuvrīhi compounds in German, i.e. exocentric structures with a possessive meaning, headed by the derivational suffixes, -er or -ig.
Holomorphic projection and duality for domains in complex projective space
Authors: Barrett David
Published: April 2015

We show that the efficiency of a natural pairing between certain projectively invariant Hardy spaces on dual strongly

C

\mathbb {C}

-convex real hypersurfaces in complex projective space is measured by the norm of the corresponding Leray transform.
Using neighborhood cohesiveness to infer interactions between protein domains
Authors: Segura Joan , Sorzano C. O. S. , Cuenca-Alba Jesus , Aloy Patrick , Carazo J. M.
Published: April 2015

Motivation: In recent years, large-scale studies have been undertaken to describe, at least partially, protein-protein interaction maps, or interactomes, for a number of relevant organisms, including human. However, current interactomes provide a somehow limited picture of the molecular details involving protein interactions, mostly because essential experimental information, especially structural data, is lacking. Indeed, the gap between structural and interactomics information is enlarging and thus, for most interactions, key experimental information is missing. We elaborate on the observation that many interactions between proteins involve a pair of their constituent domains and, thus, the knowledge of how protein domains interact adds very significant information to any interactomic analysis.

Results: In this work, we describe a novel use of the neighborhood cohesiveness property to infer interactions between protein domains given a protein interaction network. We have shown that some clustering coefficients can be extended to measure a degree of cohesiveness between two sets of nodes within a network. Specifically, we used the meet/min coefficient to measure the proportion of interacting nodes between two sets of nodes and the fraction of common neighbors. This approach extends previous works where homolog coefficients were first defined around network nodes and later around edges. The proposed approach substantially increases both the number of predicted domain-domain interactions as well as its accuracy as compared with current methods.

Availability and implementation:  http://dimero.cnb.csic.es

Contact:  jsegura@cnb.csic.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Synergistic and singular effects of river discharge and lunar illumination on dam passage of upstream migrant yellow-phase American eels
Authors: Welsh Stuart A. , Aldinger Joni L. , Braham Melissa A. , Zimmerman Jennifer L.
Published: April 2015

Monitoring of dam passage can be useful for management and conservation assessments of American eel, particularly if passage counts can be examined over multiple years. During a 7-year study (2007–2013) of upstream migration of American eels within the lower Shenandoah River (Potomac River drainage), we counted and measured American eels at the Millville Dam eel pass, where annual study periods were determined by the timing of the eel pass installation during spring or summer and removal during fall. Daily American eel counts were analysed with negative binomial regression models, with and without a year (YR) effect, and with the following time-varying environmental covariates: river discharge of the Shenandoah River at Millville (RDM) and of the Potomac River at Point of Rocks, lunar illumination (LI), water temperature, and cloud cover. A total of 17 161 yellow-phase American eels used the pass during the seven annual periods, and length measurements were obtained from 9213 individuals (mean = 294 mm TL, s.e. = 0.49, range 183–594 mm). Data on passage counts of American eels supported an additive-effects model (YR + LI + RDM) where parameter estimates were positive for river discharge (β = 7.3, s.e. = 0.01) and negative for LI (β = −1.9, s.e. = 0.34). Interestingly, RDM and LI acted synergistically and singularly as correlates of upstream migration of American eels, but the highest daily counts and multiple-day passage events were associated with increased RDM. Annual installation of the eel pass during late spring or summer prevented an early spring assessment, a period with higher RDM relative to those values obtained during sampling periods. Because increases in river discharge are climatically controlled events, upstream migration events of American eels within the Potomac River drainage are likely linked to the influence of climate variability on flow regime.
Description of IMP-31, a novel metallo-β-lactamase found in an ST235 Pseudomonas aeruginosa strain in Western Germany
Authors: Pfennigwerth Niels , Geis Gabriele , Gatermann Sören G. , Kaase Martin
Published: April 2015

Objectives

The objective of this study was to characterize a novel IMP-type metallo-β-lactamase (MBL) found in an MDR clinical isolate of Pseudomonas aeruginosa.

Methods

The P. aeruginosa isolate NRZ-00156 was recovered from an inguinal swab from a patient hospitalized in Western Germany and showed high MICs of carbapenems. MBL production was analysed by Etest for MBLs, an EDTA combined disc test and an EDTA bioassay. Typing of the isolate was performed by MLST. Genetic characterization of the new blaIMP gene was performed by sequencing the PCR products. A phylogenetic tree was constructed. The novel blaIMP gene was expressed in Escherichia coli TOP10 and the enzyme was subjected to biochemical characterization.

Results

The P. aeruginosa isolate NRZ-00156 expressed the ST235 allelic profile and was resistant to all the β-lactams tested except aztreonam. The isolate was positive for MBL production and harboured a new IMP allele, blaIMP-31, located on a disrupted class I integron [also carrying the blaOXA-35, aac(6′)-Ib, aac(3)-Ic and aphA15 genes]. Its closest relative was IMP-35, with 96.7% amino acid identity. Expression of blaIMP-31 demonstrated that E. coli TOP10 producing IMP-31 had elevated resistance to all the β-lactams tested except aztreonam. Kinetic data were obtained for both IMP-31 and IMP-1. In comparison with IMP-1, IMP-31 showed weaker hydrolytic activity against all the β-lactams tested, which resulted from lower kcat values.

Conclusions

The characterization of the new IMP-type gene blaIMP-31 from an ST235 P. aeruginosa isolate indicates an ongoing spread of highly divergent IMP-type carbapenemases in clinical P. aeruginosa strains and highlights the continuous need for the prevention of nosocomial infections caused by MDR Gram-negative bacteria.
Next-generation sequencing reveals the biological significance of the N
2,3-ethenoguanine lesion in vivo
Authors: Chang Shiou-chi , Fedeles Bogdan I. , Wu Jie , Delaney James C. , Li Deyu , Zhao Linlin , Christov Plamen P. , Yau Emily , Singh Vipender , Jost Marco , Drennan Catherine L. , Marnett Lawrence J. , Rizzo Carmelo J. , Levine Stuart S. , Guengerich F. Peter , Essigmann John M.
Published: April 2015

Etheno DNA adducts are a prevalent type of DNA damage caused by vinyl chloride (VC) exposure and oxidative stress. Etheno adducts are mutagenic and may contribute to the initiation of several pathologies; thus, elucidating the pathways by which they induce cellular transformation is critical. Although N  2,3-ethenoguanine (N  2,3-εG) is the most abundant etheno adduct, its biological consequences have not been well characterized in cells due to its labile glycosidic bond. Here, a stabilized 2′-fluoro-2′-deoxyribose analog of N  2,3-εG was used to quantify directly its genotoxicity and mutagenicity. A multiplex method involving next-generation sequencing enabled a large-scale in vivo analysis, in which both N  2,3-εG and its isomer 1,N  2-ethenoguanine (1,N  2-εG) were evaluated in various repair and replication backgrounds. We found that N  2,3-εG potently induces G to A transitions, the same mutation previously observed in VC-associated tumors. By contrast, 1,N  2-εG induces various substitutions and frameshifts. We also found that N  2,3-εG is the only etheno lesion that cannot be repaired by AlkB, which partially explains its persistence. Both εG lesions are strong replication blocks and DinB, a translesion polymerase, facilitates the mutagenic bypass of both lesions. Collectively, our results indicate that N  2,3-εG is a biologically important lesion and may have a functional role in VC-induced or inflammation-driven carcinogenesis.
The Prevalence and Associated Distress of Physical and Psychological Symptoms in Patients With Advanced Heart Failure Attending a South African Medical Center
Authors: Lokker Martine E. , Gwyther Liz , Riley Jillian P. , van Zuylen Lia , van der Heide Agnes , Harding Richard
Published: April 2015

Background:

Despite the high prevalence of heart failure in low- and middle-income countries, evidence concerning patient-reported burden of disease in advanced heart failure is lacking.

Objective:

The aim of this study is to measure patient-reported symptom prevalence and correlates of symptom burden in patients with advanced heart failure.

Methods:

Adult patients diagnosed with New York heart Association (NYHA) stage III or IV heart failure were recruited from the emergency unit, emergency ward, cardiology ward, general medicine wards, and outpatient cardiology clinic of a public hospital in South Africa. Patients were interviewed by researchers using the Memorial Symptom Assessment Scale–Short Form, a well-validated multidimensional instrument that assesses presence and distress of 32 symptoms.

Results:

A total of 230 patients (response, 99.1%), 90% NYHA III and 10% NYHA IV (12% newly diagnosed), with a mean age of 58 years, were included. Forty-five percent were women, 14% had completed high school, and 26% reported having no income. Mean Karnofsky Performance Status Score was 50%. Patients reported a mean of 19 symptoms. Physical symptoms with a high prevalence were shortness of breath (95.2%), feeling drowsy/tired (93.0%), and pain (91.3%). Psychological symptoms with a high prevalence were worrying (94.3%), feeling irritable (93.5%), and feeling sad (93.0%). Multivariate linear regression analyses, with total number of symptoms as dependent variable, showed no association between number of symptoms and gender, education, number of healthcare contacts in the last 3 months, years since diagnosis, or comorbidities. Increased number of symptoms was significantly associated with higher age (b = 0.054, P = .042), no income (b = −2.457, P = .013), and fewer hospitalizations in the last 12 months (b = −1.032, P = .017).

Conclusions:

Patients with advanced heart failure attending a medical center in South Africa experience high prevalence of symptoms and report high levels of burden associated with these symptoms. Improved compliance with national and global treatment recommendations could contribute to reduced symptom burden. Healthcare professionals should consider incorporating palliative care into the care for these patients.
Effects of Amoxicillin and Clavulanic Acid on the Spontaneous Mechanical Activity of Juvenile Rat Duodenum
Authors: Ciciora Steven L. , Williams Kent C. , Gariepy Cheryl E.
Published: April 2015

Objectives:

There are a limited number of medications for the treatment of foregut dysmotility. Enteral amoxicillin/clavulanic acid induces phase III duodenal contractions in a fasting pediatric patient. The mechanism by which this occurs is unknown. We examined the individual contributions of amoxicillin and clavulanic acid on the spontaneous mechanical activity of juvenile rat duodenum to better understand this phenomenon.

Methods:

Duodenal segments from juvenile rats were longitudinally attached to force transducers in organ baths. Samples were cumulatively exposed to amoxicillin or clavulanic acid. Separate samples were exposed to carbachol alone to assess response in both the presence and absence of amoxicillin or clavulanic acid. Basal tone, frequency, and amplitude of contractions were digitized and recorded.

Results:

The amplitude of the spontaneous contractions increased with amoxicillin. Inhibition of neuronal activity prevented this effect. Clavulanic acid did not affect the spontaneous contractions. Basal tone and the rate of contractions did not differ with either drug. Stimulation with carbachol in the presence of amoxicillin caused a statistically significant increase in the contractility compared with carbachol alone.

Conclusions:

Amoxicillin alters the spontaneous longitudinal mechanical activity of juvenile rat duodenum. Our results suggest that amoxicillin modulates the spontaneous pattern of cyclic mechanical activity of duodenal smooth muscle through noncholinergic, neurally mediated mechanisms. Our work provides an initial physiologic basis for the therapeutic use of amoxicillin in patients with gastrointestinal dysmotility.
Teaching Splinting Techniques Using a Just-in-Time Training Instructional Video
Authors: Cheng Yu-Tsun , Liu Deborah R. , Wang Vincent J.
Published: April 2015

Objective

Splinting is a multistep procedure that is seldom performed by primary care physicians. Just-in-time training (JITT) is an emerging teaching modality and can be an invaluable asset for infrequently performed procedures or in locations where teaching resources and trained professionals are limited. Our objective was to determine the utility of JITT for teaching medical students the short-arm (SA) volar splinting technique.

Methods

This was a prospective randomized controlled pilot study. An instructional video on SA volar splinting was produced. Students viewed the video or had access to standard medical textbooks (control group) immediately before applying an SA volar splint. The students were assessed for the quality of the splint via a standard 6-point skills checklist. The times required for presplinting preparation and for completion of the splint were also measured.

Results

Just-in-time training group students scored higher on the splint checklist (mean [SD], 5.45 [1.06]; 95% confidence interval [CI], 4.99–5.92 vs mean [SD], 1.58 [1.12]; 95% CI, 1.04–2.12; P < 0.0001), had higher pass rates (73%; 95% CI, 53%–93% vs 0%; P < 0.0001), and required less time (minutes) for presplinting preparation (mean [SD], 7.86 [2.45]; 95% CI, 6.78–8.94 vs mean [SD], 9.89 [0.46]; 95% CI, 9.67–10.12; P < 0.0001) compared with the control group. No difference was seen in the time required to complete a splint, successful or not.

Conclusions

In comparison with reading standard textbooks, watching a brief JITT instructional video before splinting yielded faster learning times combined with more successful procedural skills. The use of a JITT instructional video may have potential applications, including globally, as an alternative resource for teaching and disseminating procedural skills, such as SA volar splinting.
Cultural Impact on Medication Instructions: The Case of the Turkish Teaspoon
Authors: Kannan Lakshmi , Blocher Nissa
Published: April 2015

Medication errors are preventable events related to inappropriate medication use that could potentially result in patient harm. Here we present a patient encounter that has exemplified the importance of appropriate communication and the inevitable role of every individual in ensuring appropriate prescription medication use. Multidisciplinary efforts are required to ensure patient safety in today’s systems based practice. This case highlights cultural barriers to the practice of medicine and the growing need to explore and address them appropriately.
Marinobacter nitratireducens sp. nov., a halophilic and lipolytic bacterium isolated from coastal surface sea water
Authors: Vaidya Bhumika , Kumar Ravinder , Korpole Suresh , Tanuku Naga Radha Srinivas , Pinnaka Anil Kumar
Published: April 2015

A novel Gram-stain-negative, rod-shaped, motile bacterium, designated strain AK21T, was isolated from coastal surface sea water at Visakhapatnam, India. The strain was positive for oxidase, catalase, lipase,l-proline arylamidase and tyrosine arylamidase activities. The predominant fatty acids were C12:0, C12:03-OH, C16:0, C16:1ω9c, C18:1ω9cand summed feature 3 (C16:1ω7cand/or iso-C15:02-OH). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid, two unidentified phospholipids and one unidentified lipid. Q-10 was the predominant respiratory quinone. The DNA G+C content of the strain was 54.6 mol%. 16S rRNA gene sequence analysis indicated that strain AK21Twas a member of the genusMarinobacterand was closely related toMarinobacter xestospongiae, with pairwise sequence similarity of 97.2 % to the type strain, with similarity to other members of the genus of 94.0–96.8 %. The mean DNA–DNA relatedness of strain AK21TwithM. xestospongiaeJCM 17469Twas 34.5 %, and relatedness withMarinobacter mobilisJCM 15154Twas 40.5 %. Phylogenetic analysis showed that strain AK21Tclustered with the type strains ofM. xestospongiaeandM. mobilisat distances of 2.9 and 2.8 % (97.1 and 97.2 % similarity), respectively. Based on the phenotypic characteristics and on phylogenetic inference, it appears that strain AK21Trepresents a novel species of the genusMarinobacter, for which the nameMarinobacter nitratireducenssp. nov. is proposed. The type strain ofMarinobacter nitratireducensis AK21T( = MTCC 11704T = JCM 18428T).
The Cardioprotective Effect of Icariin on Ischemia–Reperfusion Injury in Isolated Rat Heart: Potential Involvement of the PI3K‐Akt Signaling Pathway
Authors: Ke Zunping , Liu Jingjing , Xu Peng , Gao Aimei , Wang Lei , Ji Lijuan
Published: April 2015

Aims

Icariin (ICA), a flavonoid isolated from epimedii, has been reported to have potential protective effects on the cardiovascular system. This study is to investigate the effect and the underlying mechanisms of ICA on ischemia/reperfusion (I/R) injury.

Methods

Wister rat hearts were subjected to I/R using Langendorff perfusion system. Cardiac function, myocardial infarct size, lactate dehydrogenase (LDH), and creatine kinase‐MB (CK‐MB) activities in coronary effluent, and superoxide dismutase (SOD) and malondialdehyde (MDA) content in heart tissue and cardiomyocyte apoptosis were assayed.

Results

Compared with the I/R group, ICA treatment significantly improved cardiac function, decreased myocardial infarct size, enzyme activity, oxidative stress, and apoptosis. In addition, ICA treatment lead to an increased p‐Akt level, which was partially reversed by LY294002, a PI3K pathway inhibitor.

Conclusion

Our study suggests that ICA has a cardioprotective effect against I/R injury, which is associated with its antioxidative and anti‐apoptotic effect, at least partially, through the activation of PI3K‐Akt signaling pathway.
Sociodemographic characteristics and attitudes towards motherhood among single women compared with cohabiting women treated with donor semen – a Danish multicenter study
Authors: Salomon Maria , Sylvest Randi , Hansson Helena , Nyboe Andersen Anders , Schmidt Lone
Published: April 2015

Objective

To examine sociodemographic characteristics, family backgrounds, reproductive histories, and attitudes towards motherhood in single vs. cohabiting women seeking treatment with donor semen.

Design

Baseline data collection in a multicenter cohort study.

Setting

All nine public fertility clinics in Denmark.

Sample

In total n = 311 childless women initiating assisted reproduction using donor semen.

Methods

Self‐reported questionnaire responses from n = 184 single women seeking treatment by using donor semen were compared with responses from n = 127 cohabiting women.

Main outcome measures

Sociodemographic characteristics, family backgrounds, reproductive histories, attitudes towards motherhood.

Results

Single women were 3.5 years older on average when initiating treatment compared with cohabiting women. No significant differences were found regarding sociodemographic characteristics, previous long‐term relationships, previous pregnancies, or attitudes towards motherhood between single women and cohabiting women. The vast majority of single women wanted to achieve parenthood with a partner, 85.8% wished to have a partner in the future, and approximately half of them preferred for a partner to take parental responsibilities.

Conclusions

In this study single women seeking treatment with donor semen in the public health system did not differ from cohabiting women, except that they were older. To be a single mother by choice is not their preferred way of parenthood, but a solution they needed to accept.
Risk stratification with cervical length and fetal fibronectin in women with threatened preterm labor before 34 weeks and not delivering within 7 days
Authors: Hermans Frederik J.R. , Bruijn Merel M.C. , Vis Jolande Y. , Wilms Femke F. , Oudijk Martijn A. , Porath Martina M. , Scheepers Hubertina C.J. , Bloemenkamp Kitty W.M. , Bax Caroline J. , Cornette Jérôme M.J. , Nij Bijvanck Bas W.A. , Franssen Maureen T.M. , Vandenbussche Frank P.H.A. , Kok Marjolein , Grobman William A. , Van Der Post Joris A.M. , Bossuyt Patrick M.M. , Opmeer Brent C. , Mol Ben Willem J. , Schuit Ewoud , Van Baaren Gert‐Jan
Published: April 2015

Objective

To stratify the risk of spontaneous preterm delivery using cervical length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor who remained pregnant after 7 days.

Design

Prospective observational study.

Setting

Nationwide cohort of women with threatened preterm labor from the Netherlands.

Population

Women with threatened preterm labor between 24 and 34 weeks with a valid CL and fFN measurement and remaining pregnant 7 days after admission.

Methods

Kaplan–Meier and Cox proportional hazards models were used to estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery.

Main outcome measures

Spontaneous delivery between 7 and 14 days after initial presentation and spontaneous preterm delivery before 34 weeks.

Results

The risk of delivery between 7 and 14 days was significantly increased for women with a CL < 15 mm or a CL ≥15 to <30 mm and a positive fFN, compared with women with a CL ≥30 mm: HR 22.3 [95% confidence interval (CI) 2.6–191] and 14 (95% CI 1.8–118), respectively. For spontaneous preterm delivery before 34 weeks the risk was increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6–15)] or with a CL ≥15 to <30 mm with either positive fFN [HR 3.6 (95% CI 1.5–8.7)] or negative fFN [HR 3.0 (95% CI 1.2–7.1)] compared with women with a CL ≥ 30 mm.

Conclusions

In women remaining pregnant 7 days after threatened preterm labor, CL and fFN results can be used in risk stratification for spontaneous delivery.
Support for down‐staging of pregnancy‐associated cervical cancer
Authors: Kärrberg Cecilia , Rådberg Thomas , Holmberg Erik , Norström Anders
Published: April 2015

Objective

To evaluate all cases of cervical cancer associated with pregnancy during 16 years in the Western Region of Sweden.

Design

Retrospective, descriptive cohort study.

Setting and population

All women with cervical cancer, diagnosed during pregnancy or within 6 months after parturition, between 1993 and 2008.

Methods

The study was based on data from different registers and medical records.

Main outcome measures

Incidence, diagnostic measures, treatment and outcome of disease.

Results

Cervical cancer was diagnosed in 47 women (15.6/100 000 deliveries). Sixteen women had abnormal vaginal bleeding and/or discharge. The other women were asymptomatic and diagnosed by abnormal cervical smear or clinical signs at vaginal examination. Nine women had atypical squamous cells of uncertain significance as presenting by cervical atypia. Twenty‐two women had stage IA, 17 stage IB1, six stage IB2 and two stage IIA cancer. Cancer was diagnosed in the first trimester in two, in the second trimester in 14, in the third trimester in five and postpartum in 26 women. Histology revealed squamous cell carcinoma in 36 women, adenocarcinoma in eight, and adenosquamous carcinoma in three. Twenty women underwent cesarean section due to diagnosed or clinically suspected cancer, combined with the Wertheim–Meigs radical hysterectomy in six women. Sixteen women with stage IA1 cancer without signs of vascular invasion underwent conization as definitive therapy. Six women died of the disease.

Conclusion

Early detection of cervical cytological atypia and proper follow‐up during pregnancy led to detection of a high proportion of stage I cancer cases, which could be cured with fertility‐sparing therapy.
Presenting phenotype of paediatric inflammatory bowel disease in Wessex, Southern England 2010–2013
Authors: Ashton JJ , Coelho T , Ennis S , Batra A , Afzal NA , Beattie RM
Published: April 2015

Aim

There has been at least a twofold increase in the incidence of paediatric inflammatory bowel disease (PIBD) over the last 20 years; we report the presenting features from 2010 to 2013 and compare with previous data.

Methods

All patients diagnosed with PIBD at University Hospitals Southampton from 2010 to 2013 were identified from an in‐house database. Data were obtained from paper and electronic notes. Height, weight and BMI SDS are presented as median values (95% CI).

Results

One hundred and seventy‐two patients were included (median age at diagnosis 13.5, 115 male); Crohn's disease (CD) – 107, UC – 50, inflammatory bowel disease unclassified (IBDU) – 15. The most common presenting features of CD were abdominal pain (86%), diarrhoea (78.5%) and weight loss (56.1%); 42.1% of patients had all three. In UC blood in stool (92%), diarrhoea (92%) and abdominal pain (88%) were the most common; all three in 76% of patients. CD presented with ileocolonic disease in 52.5%. UC presented with pancolitis in 64%. There was growth delay in CD: height −0.37 (−0.60 to −0.14); weight −1.09 (−1.35 to −0.83). Growth was maintained in UC: height 0.53 (0.19 to 0.87); weight 0.14 (−0.20 to 0.48).

Conclusion

Paediatric inflammatory bowel disease phenotype remains as extensive despite increasing incidence. Although the classical phenotype is common, a reasonable proportion present with atypical features, normal growth and normal blood markers.
Ammonium increases Ca2+ signalling and upregulates expression of Cav1.2 gene in astrocytes in primary cultures and in the in vivo brain
Authors: Wang F. , Du T. , Liang C. , Verkhratsky A. , Peng L.
Published: April 2015

Aim

The primary aim of this study was to identify the effects of hyperammonaemia on functional expression of Cav1.2 L‐type Ca2+ channels in astroglia.

Methods

Primary cultures of mouse astrocytes were used to study effects of chronic treatment (1–5 days) with ammonium chloride, at 1, 3 and 5 mm on depolarization‐induced increases in free cytosolic Ca2+ concentration ([Ca2+]i, measured with Fura‐2 based microfluorimetry) in control conditions and following treatment with the L‐type Ca2+ channel inhibitor, nifedipine, or with ryanodine receptor inhibitor, ryanodine. Expression of Cav1.2 mRNA was identified with RT‐PCR, whereas protein content was determined by Western blotting. Sustained hyperammonaemia in vivo was induced by daily injections of urease (33 units kg body weight−1, i.p.) for 3 days.

Results

Depolarization‐induced [Ca2+]i transients sensitive to nifedipine (peak of the response) and to ryanodine (plateau phase) were significantly increased in astrocytes chronically exposed to ammonium. The ammonium‐induced increase in Ca2+ influx in astrocytes resulted from an upregulation of Cav1.2 channel's expression detected at mRNA and protein levels. Increase in Cav1.2 expression was prevented by ouabain antagonist canrenone. Similar upregulation of Cav1.2 gene expression was found in the brains of adult mice subjected to intraperitoneal injection of urease. In transgenic mice tagged with an astrocyte‐specific or neurone‐specific markers and treated with intraperitoneal injections of urease, the fluorescence‐activated cell sorting of neurones and astrocytes demonstrated that Cav1.2 mRNA expression was upregulated in astrocytes, but not in neurones.

Conclusions

Ammonium‐induced deregulation of astroglial Ca2+ signalling, is, in part, associated with upregulation of Cav1.2 L‐type calcium channels.
Improving multivariable prostate cancer risk assessment using the Prostate Health Index
Authors: Foley Robert W. , Gorman Laura , Sharifi Neda , Murphy Keefe , Moore Helen , Tuzova Alexandra V. , Perry Antoinette S. , Murphy T. Brendan , Lundon Dara J. , Watson R. William G.
Published: April 2015

Objectives

To analyse the clinical utility of a prediction model incorporating both clinical information and a novel biomarker, p2PSA, in order to inform the decision for prostate biopsy in an Irish cohort of men referred for prostate cancer assessment.

Patients and Methods

Serum isolated from 250 men from three tertiary referral centres with pre‐biopsy blood draws was analysed for total prostate‐specific antigen (PSA), free PSA (fPSA) and p2PSA. From this, the Prostate Health Index (PHI) score was calculated (PHI = (p2PSA/fPSA)*√tPSA). The men's clinical information was used to derive their risk according to the Prostate Cancer Prevention Trial (PCPT) risk model. Two clinical prediction models were created via multivariable regression consisting of age, family history, abnormality on digital rectal examination, previous negative biopsy and either PSA or PHI score, respectively. Calibration plots, receiver‐operating characteristic (ROC) curves and decision curves were generated to assess the performance of the three models.

Results

The PSA model and PHI model were both well calibrated in this cohort, with the PHI model showing the best correlation between predicted probabilities and actual outcome. The areas under the ROC curve for the PHI model, PSA model and PCPT model were 0.77, 0.71 and 0.69, respectively, for the prediction of prostate cancer (PCa) and 0.79, 0.72 and 0.72, respectively, for the prediction of high grade PCa. Decision‐curve analysis showed a superior net benefit of the PHI model over both the PSA model and the PCPT risk model in the diagnosis of PCa and high grade PCa over the entire range of risk probabilities.

Conclusion

A logical and standardized approach to the use of clinical risk factors can allow more accurate risk stratification of men under investigation for PCa. The measurement of p2PSA and the integration of this biomarker into a clinical prediction model can further increase the accuracy of risk stratification, helping to better inform the decision for prostate biopsy in a referral population.
Modulation of pre‐attentive spectro‐temporal feature processing in the human auditory system by HD‐tDCS
Authors: Heimrath Kai , Breitling Carolin , Krauel Kerstin , Heinze Hans‐Jochen , Zaehle Tino
Published: April 2015

The present study examined the functional lateralization of the human auditory cortex (AC) for pre‐attentive spectro‐temporal feature processing. By using high‐definition transcranial direct current stimulation (HD‐tDCS), we systematically modulated neuronal activity of the bilateral AC. We assessed the influence of anodal and cathodal HD‐tDCS delivered over the left or right AC on auditory mismatch negativity (MMN) in response to temporal as well as spectral deviants in 12 healthy subjects. The results showed that MMN to temporal deviants was significantly enhanced by anodal HD‐tDCS applied over the left AC only. Our data indicate a left hemispheric dominance for the pre‐attentive processing of low‐level temporal information.
SOX7 interferes with β‐catenin activity to promote neuronal apoptosis
Authors: Wang Chong , Qin Lina , Min Zhiqun , Zhao Yiwei , Zhu Lin , Zhu Jing , Yu Shaojun
Published: April 2015

SOX7 mediates various developmental processes. However, its role in neuronal apoptosis remains unclear. In the present study, we investigated the expression pattern and role of SOX7 in potassium deprivation‐induced rat cerebellar granule neuron apoptosis. Our results showed that both mRNA and protein levels of SOX7 were upregulated when potassium was deprived. SOX7 overexpression promoted neuronal apoptosis, whereas knockdown of SOX7 protected neurons against apoptosis. Moreover, we found that β‐catenin activity was suppressed during apoptosis and that β‐catenin inhibition was crucial for potassium deprivation‐induced neuronal apoptosis. This suppression was mediated by an interaction between SOX7 and β‐catenin but not by protein degradation. Lastly, we showed that β‐catenin inhibition mediated the pro‐apoptotic effect of SOX7. Together, our findings demonstrated that SOX7 interfered with β‐catenin activity to promote neuronal apoptosis, which acted as a novel signaling mechanism in neuronal cell death.
Mutation ofCHRNA2in a family with benign familial infantile seizures: Potential role of nicotinic acetylcholine receptor in various phenotypes of epilepsy
Authors: Trivisano Marina , Terracciano Alessandra , Milano Teresa , Cappelletti Simona , Pietrafusa Nicola , Bertini Enrico Silvio , Vigevano Federico , Specchio Nicola
Published: April 2015

Nicotinic acetylcholine receptor genes are involved mainly in nocturnal frontal epilepsy. Despite extensive studies, to date, the α2 subunit did not show a strong association with this peculiar epileptic phenotype. We reportCHRNA2missense mutation in a family with benign familial infantile seizures (BFIS). TrueSeq Custom Amplicon (TSCA) sequencing approach was used to screen 10 ion channel genes in patients with idiopathic epilepsies.TSCArevealed a heterozygous single‐nucleotide substitution inCHRNA2gene (c.1126 C>T; p. Arg376Trp) that segregated in a family withBFIS; based on bio‐informatics inspection, the change was predicted to be pathogenic. The investigated family includes parents and their three daughters. In affected individuals, seizures started between 6 and 24 months of age. Seizures were mainly in cluster and well‐controlled. Outcome was good in all subjects. Even if nicotinic acetylcholine receptor genes are traditionally associated with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), this single‐family description can open new possibilities in the genetic diagnosis, molecular characterization, and management ofCHRNA2‐related epilepsy. The pathogenic conversion of arginine 376 to tryptophan alters all of these interactions in the cytoplasmic domain, never reported to be involved in epileptogenic mechanism. Further functional tests will be necessary to strongly relateCHRNA2mutation withBFISphenotype.
A product of RpfB and RipA joint enzymatic action promotes the resuscitation of dormant mycobacteria
Authors: Nikitushkin Vadim D. , Demina Galina R. , Shleeva Margarita O. , Guryanova Svetlana V. , Ruggiero Alessia , Berisio Rita , Kaprelyants Arseny S.
Published: April 2015

Resuscitation‐promoting factor proteins (Rpfs) are known to participate in reactivating the dormant forms of actinobacteria. Structural analysis of the Rpf catalytic domain demonstrates its similarity to lysozyme and to lytic transglycosylases – the groups of enzymes that cleave the β‐1,4‐glycosidic bond between N‐acetylmuramic acid (MurNAc) and GlcNAc, and concomitantly form a 1,6‐anhydro ring at the MurNAc residue. Analysis of the products formed from mycobacterial peptidoglycan hydrolysis reactions containing a mixture of RpfB and resuscitation‐promoting factor interacting protein (RipA) allowed us to identify the suggested product of their action – N‐acetylglucosaminyl‐β(1→4)‐N‐glycolyl‐1,6‐anhydromuramyl‐l‐alanyl‐d‐isoglutamate. To identify the role of this resulting product in resuscitation, we used a synthetic 1,6‐anhydrodisaccharide‐dipeptide, and tested its ability to stimulate resuscitation by using the dormant Mycobacterium smegmatis model. It was found that the disaccharide‐dipeptide was the minimal structure capable of resuscitating the dormant mycobacterial cells over the concentration range of 9–100 ng·mL−1. The current study therefore provides the first insights into the molecular mechanism of resuscitation from dormancy involving a product of RpfB/RipA‐mediated peptidoglycan cleavage.
Farmed meagre, Argyrosomus regius of three different sizes: what are the differences in flesh quality and muscle cellularity?
Authors: Saavedra Margarida , Pereira Teresa G. , Grade Ana , Barbeiro Mónica , Pousão‐Ferreira Pedro , Quental‐Ferreira Hugo , Nunes Maria Leonor , Bandarra Narcisa , Gonçalves Amparo
Published: April 2015

Larger meagre are more common in the market but, recently, smaller fish have started to be commercialised as well. This study aims to evaluate flesh quality and muscle cellularity of meagre of three different sizes: 800, 1500 and 2500 g. Results showed a higher fat content in larger fish (2.9% compared to 1.3% in small fish), and that texture was not affected by fish size. In terms of muscle cellularity, a higher frequency of smaller fibres was observed in 800 and 1500 g (33% compared to 18% in 2500 g) meagre, whereas in 2500 g meagre, there was a higher frequency of larger fibres. Muscle fibre density was reduced with fish weight (431 and 297 fibres mm−2 for 800 and 2500 g meagre, respectively). In conclusion, this study shows that meagre of different weights are different in terms of fat content and muscle cellularity and that 800 g meagre seems to have a good potential for being commercialised.
Abortion and Compelled Physician Speech
Authors: Orentlicher David
Published: April 2015

As states increasingly impose informed consent mandates on abortion providers, the required disclosures bring two well-established legal doctrines into conflict — the First Amendment’s freedom of speech and the physician’s duty to obtain informed consent.

On one hand, the First Amendment provides for a broad freedom of speech, under which government may neither prevent people from voicing their own views, nor compel individuals to voice the government’s views. As the Supreme Court observed in Wooley v. Maynard, the First Amendment protects “both the right to speak freely and the right to refrain from speaking at all.” When legislatures tell physicians what they must disclose to their patients, the physicians lose their right not to speak.
The First Amendment and Physician Speech in Reproductive Decision Making
Authors: Suter Sonia M.
Published: April 2015

The regulation of medicine has long been recognized as within the state’s police powers. Yet when the state regulates physicians’ professional speech, it potentially raises First Amendment concerns. Nowhere is this truer than in the abortion context, where state legislatures have attempted to influence women’s reproductive decisions with informed consent requirements. Although the Supreme Court, inPlanned Parenthood of Se. Pa. v. Casey, found a mandated disclosure provision constitutional some 20 years ago, it offered little to clarify the scope and reach of the First Amendment issues that arise with abortion informed consent laws.

SinceCaseywas decided, legislatures have enacted a range of informed consent laws that impose even more stringent abortion informed consent regulations than the provisions at issue inCasey.
A Matter of Context: Casey and the Constitutionality of Compelled Physician Speech
Authors: Gaylord Scott W.
Published: April 2015

The First Amendment states that “Congress shall make no law…abridging the freedom of speech.” Given the myriad ways in which freedom of speech can be implicated, the United States Supreme Court has not adopted a single standard for reviewing First Amendment speech claims. With respect to compelled speech, the Court has instructed that “context” is dispositive. When the government attempts to “prescribe what shall be orthodox in politics, nationalism, religion, or other matters of opinion or force citizens to confess by word or act their faith therein,” the Court applies strict scrutiny. When, however, “the State has a significant role to play in regulating” a particular context, government-compelled disclosures may be subject to a lower standard of review: “When a state regulation implicates First Amendment rights, the court must balance those interests against the State’s legitimate interest in regulating the activity in question.”
Global Justice and Health Systems Research in Low- and Middle-Income Countries
Authors: Pratt Bridget , Hyder Adnan A.
Published: April 2015

More than a decade ago, Solomon Benatar and Peter Singer argued that “a new, proactive research ethics…must ultimately be concerned with reducing inequities in global health and achieving justice in health research and health care.” Towards this objective, a limited amount of recent scholarship has started to consider whether a theoretical basis exists for the position that international research should help promote global health equity and, if so, what the implications are for its conduct. Theories of justice from political philosophy establish obligations for parties in high-income countries to improve the health of parties in low- and middle-income countries (LMICs). These theories have been shown to provide grounds for the claim that international research should be conducted to advance justice in global health. What this means for research actors from high-income countries is the focus of a recently proposed ethical framework: “research for health justice.”
State Health Department Employees, Policy Advocacy, and Political Campaigns: Protections and Limits under the Law
Authors: Frattaroli Shannon , Pollack Keshia M. , Young Jessica L. , Vernick Jon S.
Published: April 2015

State health departments are at the core of the United States (U.S.) public health infrastructure. Surveillance to monitor trends in disease and injury; the development, coordination, and delivery of services; and public education are some of the core functions health department employees oversee every day. As such, agencies and their employees are well positioned to inform policy decisions that affect the public’s health. However, little is known about the role of health department staff — a sizeable proportion of the public health workforce — as advocates for public health policies, independent of their agency roles. Anecdotally, some health department employees with whom we have spoken expressed reluctance to engage in policy advocacy for fear of violating little known or understood agency or state rules.
Harnessing the Public Health Power of Model Codes to Increase Drinking Water Access in Schools and Childcare
Authors: Wilking Cara L. , Cradock Angie L. , Gortmaker Steven L.
Published: April 2015

Drinking water is an important health behavior to support overall child health. Research indicates that children are consuming too little water and too many sugary drinks. Overconsumption of sugary drinks increases child risk for the epidemics of obesity and diet-related chronic diseases like type-II diabetes, stroke, and heart disease. Increasing access to appealing, low-cost drinking water in schools and childcare where children spend much of their time supports efforts to reduce sugary drink consumption. Drinking water infrastructure is key to water access in childcare and schools. In 2012-2013, almost one-third of permanent U.S. school buildings had plumbing systems in fair or poor condition, and almost 40 percent had major renovations or repairs planned.3 Basic plumbing standards for new construction and major renovations or repairs are contained in state and local plumbing codes, and many of these codes are derived from model codes established by private organizations. This article describes the model code process and intervention points where the public health community can work to improve plumbing standards in school buildings and childcare centers.
Mental Health Emergency Detentions and Access to Firearms
Authors: Vernick Jon S. , McGinty Emma E. , Rutkow Lainie
Published: April 2015

Following the tragic shootings in Newtown (Connecticut), Aurora (Colorado), Isla Vista (California) and others, increased national attention has focused on the relationship between mental illness and gun violence. While some have called for enhanced regulation of firearm possession by persons with mental illness, others have argued that such actions would be ineffective and enhance stigma associated with mental illness while discouraging treatment seeking.
Is Sharing De-Identified Data Legal? The State of Public Health Confidentiality Laws and Their Interplay with Statistical Disclosure Limitation Techniques
Authors: Richardson Victor , Milam Sallie , Chrysler Denise
Published: April 2015

The diversity of state confidentiality laws governing public health data presents a significant challenge for public health initiatives. This challenge is further complicated by the array of confidentially laws that are relevant within a state as disclosure and usage standards vary depending upon data holder, type, and source. These laws often have not been updated to address modern confidentiality risks such as unlawful data linkage or breach, leaving many public health organizations without clear guidance in the contentious area of individual privacy. To address these challenges, public health organizations have increasingly turned to the science of de-identification, but whether de-identification adequately meets the many and varied state confidentiality legal requirements remains an unanswered question.
Bridging the Gap between Science and Law: The Example of Tobacco Regulatory Science
Authors: Berman Micah L. , Kim Annice E.
Published: April 2015

In the 20th century, public health was responsible for most of the 30-year increase in average life expectancy in the United States.1 Most of the significant advances in public health (e.g., vaccinations, water fluoridation) required the combined effort of scientists and attorneys. Scientists identified public health threats and the means of controlling them, but attorneys and policymakers helped convert those scientific discoveries into laws that could change the behavior of industries or individuals at a population level. In tobacco control, public health scientists made the groundbreaking discovery that smoking caused lung cancer, but attorneys and policymakers developed and implemented the policies and litigation strategies that helped reduce smoking rates by more than half over the past 50 years.