bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic resistance in human peri‐implantitis microbiota
Authors: Rams Thomas E. , Degener John E. , van Winkelhoff Arie J.
Published: April 2013

Objectives

Because antimicrobial therapy is often employed in the treatment of infectious dental implant complications, this study determined the occurrence of in vitro antibiotic resistance among putative peri‐implantitis bacterial pathogens.

Methods

Submucosal biofilm specimens were cultured from 160 dental implants with peri‐implantitis in 120 adults, with isolated putative pathogens identified to species level, and tested in vitro for susceptibility to 4 mg/l of doxycycline, 8 mg/l of amoxicillin, 16 mg/l of metronidazole, and 4 mg/l of clindamycin. Findings for amoxicillin and metronidazole were combined post‐hoc to identify peri‐implantitis species resistant to both antibiotics. Gram‐negative enteric rods/pseudomonads were subjected to ciprofloxacin disk diffusion testing.

Results

One or more cultivable submucosal bacterial pathogens, most often Prevotella intermedia/nigrescens or Streptococcus constellatus, were resistant in vitro to clindamycin, amoxicillin, doxycycline, or metronidazole in 46.7%, 39.2%, 25%, and 21.7% of the peri‐implantitis subjects, respectively. Only 6.7% subjects revealed submucosal test species resistant in vitro to both amoxicillin and metronidazole, which were either S. constellatus (one subject) or ciprofloxacin‐susceptible strains of gram‐negative enteric rods/pseudomonads (seven subjects). Overall, 71.7% of the 120 peri‐implantitis subjects exhibited submucosal bacterial pathogens resistant in vitro to one or more of the tested antibiotics.

Conclusions

Peri‐implantitis patients frequently yielded submucosal bacterial pathogens resistant in vitro to individual therapeutic concentrations of clindamycin, amoxicillin, doxycycline, or metronidazole, but only rarely to both amoxicillin and metronidazole. Due to the wide variation in observed drug resistance patterns, antibiotic susceptibility testing of cultivable submucosal bacterial pathogens may aid in the selection of antimicrobial therapy for peri‐implantitis patients.
Ligation of the intersphincteric fistula tract in the management of anal fistula. A systematic review
Authors: Yassin N. A. , Hammond T. M. , Lunniss P. J. , Phillips R. K. S.
Published: March 2013

Aim

Over the last 5 years, the ligation of the intersphincteric fistula tract (LIFT) procedure has become increasingly popular as a sphincter‐preserving technique for the treatment of anal fistula. The aim of this article was to review the published literature on the LIFT procedure.

Method

The Cochrane database and EMBASE were searched from January 1980 to November 2012, and PubMed from January 1966 to November 2012. All peer‐reviewed studies that investigated the LIFT procedure for the treatment of anal fistula were eligible for inclusion. Technical notes, commentaries, letters and meeting abstracts were excluded. The primary outcome measured was the overall fistula closure rate in relation to the length of follow‐up.

Results

Twenty‐nine articles were originally identified using the search criteria. Thirteen were finally included for analysis. Sample sizes ranged from 18 to 93 patients, with a pooled total of 498. Most fistulae, 494 (99%), were of cryptoglandular aetiology, of which 470 (94%) were transsphincteric. Overall success rates ranged from 40 to 95%, with a pooled success of 71% (352 of 495 patients; 3 of 498 were lost to follow‐up). Follow‐up ranged from 1 to 55 months, with a reported mean or median of 4 to 19.5 months. One hundred and eighty‐three patients were formally assessed for continence, out of whom 11 (6%) had a minor disturbance.

Conclusion

Overall the systematic review shows that the LIFT procedure appears to be an effective sphincter‐conserving approach for the treatment of transsphincteric anal fistula with a pooled healing rate of 71% over a mean or median follow‐up period ranging from 4 to 19.5 months.
Comprehensive and Rapid Assessment of Carotid Plaques in Acute Stroke Using a New Single Sweep Method for Three‐Dimensional Carotid Ultrasound
Authors: Kalashyan Harapet , Saqqur Maher , Shuaib Ashfaq , Romanchuk Helen , Nanda Navin C. , Becher Harald
Published: April 2013

We describe a 68‐year‐old man with acute stroke in whom the newly developed single sweep method for three‐dimensional (3D) carotid ultrasound provided a rapid and comprehensive assessment of atherosclerotic plaque burden in the internal carotid artery. The two‐dimensional duplex carotid scan diagnosed 50–69% stenosis, and with the three‐dimensional method, the markedly hypoechogenic plaque (total volume 1.42 mL) was shown to occupy 77% of the total arterial volume (1.84 mL), consistent with severe lesion. The ultrasound findings were confirmed by computed tomographic angiography and subsequent carotid endarterectomy. The new single sweep 3D carotid ultrasound has the potential to become a valuable clinical tool in the assessment of stroke patients.
The Incremental Value of Three‐Dimensional Transthoracic Echocardiography in Adult Congenital Heart Disease
Authors: Bleich Steven , Nanda Navin C. , Hage Fadi G.
Published: April 2013

Imaging with echocardiography is useful in diagnosing congenital heart disease (CHD). Two‐dimensional (2D) transthoracic echocardiography (TTE) has been the standard cardiac imaging modality, but it forces the reader to mentally create the three‐dimensional (3D) cardiac anatomy to understand these complex diseases. 3D TTE, which has relatively recently emerged to address this limitation, is capable of providing clear and dynamic 3D views of these anatomic defects and offers more insight on how to manage them. This review article will address the benefit of utilizing 3D TTE for proper characterization of different types of CHD in the adult and as a guide to appropriate treatment.
What predicts enduring intractability in children who appear medically intractable in the first 2 years after diagnosis?
Authors: Wirrell Elaine C. , Wong‐Kisiel Lily C.‐L. , Mandrekar Jay , Nickels Katherine C.
Published: April 2013

Purpose

In a population‐based retrospective cohort of children with newly diagnosed epilepsy, to determine (1) what proportion meet criteria for early medical intractability, and (2) predictors of enduring intractability.

Methods

Children with newly diagnosed epilepsy between 1980 and 2009 while resident in Olmsted County, MN, and followed >36 months, were stratified into groups based on both early medical intractability (“apparent” medical intractability in the first 2 years) and enduring intractability (persisting intractability at final follow‐up or having undergone surgery for intractable epilepsy), and variables predicting these outcomes were evaluated.

Key Findings

Three hundred eighty‐one children were included, representing 81% of our cohort with newly diagnosed epilepsy. Seventy five (19.7%) had early medical intractability, and predictors of this outcome on multivariable analysis were neuroimaging abnormality (risk ratio, 2.70; p = 0.0004), abnormal neurologic examination at diagnosis (risk ratio, 1.87; p = 0.015), and mode of onset (association was significant for focal vs. generalized onset [risk ratio, 0.25; p < 0.0001] but not unknown vs. generalized onset [p = 0.065]). After a median follow‐up of 11.7 years, 49% remained intractable, 8% had rare seizures (≤ every 6 months), and the remainder were seizure‐free. The only factor predicting enduring intractability on multivariable analysis was neuroimaging abnormality (risk ratio, 7.0; p = 0.0006).

Significance

Although a significant minority of children with early medical intractability ultimately achieved seizure control without surgery, those with an abnormal imaging study did poorly. For this subgroup, early surgical intervention is strongly advised to limit comorbidities of ongoing, intractable seizures. Conversely, a cautious approach is suggested for those with normal imaging, as most will remit with time.
Double site saturation mutagenesis of the human cytochrome P450 2D6 results in regioselective steroid hydroxylation
Authors: Geier Martina , Braun Andreas , Fladischer Patrik , Stepniak Piotr , Rudroff Florian , Hametner Christian , Mihovilovic Marko D. , Glieder Anton
Published: March 2013

The human cytochrome P450 2D6 (CYP2D6) is one of the major human drug metabolizing enzymes and acts preferably on substrates containing a basic nitrogen atom. Testosterone − just as other steroids − is an atypical substrate and only poorly metabolized by CYP2D6. The present study intended to investigate the influence of the two active site residues 216 and 483 on the capability of CYP2D6 to hydroxylate steroids such as for example testosterone. All 400 possible combinatorial mutations at these two positions have been generated and expressed individually in Pichia pastoris. Employing whole‐cell biotransformations coupled with HPLC‐MS analysis the testosterone hydroxylase activity and regioselectivity of every single CYP2D6 variant was determined. Covering the whole sequence space, CYP2D6 variants with improved activity and so far unknown regio‐preference in testosterone hydroxylation were identified. Most intriguingly and in contrast to previous literature reports about mutein F483I, the mutation F483G led to preferred hydroxylation at the 2β‐position, while the slow formation of 6β‐hydroxytestosterone, the main product of wild‐type CYP2D6, was further reduced. Two point mutations have already been sufficient to convert CYP2D6 into a steroid hydroxylase with the highest ever reported testosterone hydroxylation rate for this enzyme, which is of the same order of magnitude as for the conversion of the standard substrate bufuralol by wild‐type CYP2D6. Furthermore, this study is also an example for efficient human CYP engineering in P. pastoris for biocatalytic applications and to study so far unknown pharmacokinetic effects of individual and combined mutations in these key enzymes of the human drug metabolism.
Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double‐blind, placebo‐controlled trial
Authors: Sakaida Isao , Kawazoe Seiji , Kajimura Kozo , Saito Takafumi , Okuse Chiaki , Takaguchi Koichi , Okada Mitsuru , Okita Kiwamu ,   ASCITES‐DOUBLEBLIND Study Group
Published: April 2013

Aim

Hepatic edema is manifested by ascites, lower limb edema and intolerable symptoms. Some patients insufficiently respond to the conventional diuretic therapy. Therefore, a novel therapeutic option is required. We conducted a phase 3 study to confirm therapeutic effect of tolvaptan on hepatic edema associated with liver cirrhosis.

Methods

In our multicenter, randomized, double‐blind, placebo‐controlled trial, liver cirrhosis patients who showed insufficient response to conventional diuretics were randomly assigned to 7‐day administration of either tolvaptan at 7.5 mg/day or placebo as an add‐on therapy to conventional diuretics. The primary outcome was change in bodyweight from baseline.

Results

Of 164 eligible patients, 84 were assigned to tolvaptan and 80 to placebo. Change in bodyweight from baseline on the final dosing day was −0.44 kg (standard deviation [SD], 1.93) in the placebo group and −1.95 kg (SD, 1.77) in the tolvaptan group (P < 0.0001). Improvement rates for lower limb edema and ascites‐related clinical symptoms were higher with tolvaptan than with placebo. Even in patients with low serum albumin (<2.5 g/dL), decrease in bodyweight was greater with tolvaptan than with placebo (P = 0.0163). In addition, tolvaptan significantly increased serum sodium concentration from baseline.

Conclusion

Add‐on therapy with tolvaptan was effective for the treatment of hepatic edema and ascites‐related clinical symptoms. Furthermore, tolvaptan is expected to improve low serum sodium concentration and to exert its effect regardless of serum albumin level. Add‐on therapy with tolvaptan is therefore considered to be a novel therapeutic option for hepatic edema.
Merger in Higher Education: learning from Experiences
Authors: Drowley Melinda J. , Lewis Duncan , Brooks Simon
Published: April 2013

Political pressure to reduce the number of higher education institutions in Wales has been sustained for over a decade by three successive ministers for education, two of whom, Jane Davidson and the current incumbent, Leighton Andrews, have left the Welsh sector in no doubt about the strength of their personal commitment to the policy of reconfiguration and collaboration. In this paper, an attempt is made to understand and explain how this policy was experienced by some of the people most closely affected by the recent merger between the Royal Welsh College of Music and Drama and the University of Glamorgan in South East Wales. Some of the lessons learned in this particular context are elucidated in the hope that they might be of assistance to both policy‐makers and members of higher education institutions elsewhere that are contemplating merger.
Immunohistochemistry using the BRAF V600E mutation‐specific monoclonal antibody VE1 is not a useful surrogate for genotyping in colorectal adenocarcinoma
Authors: Adackapara Cheryl A , Sholl Lynette M , Barletta Justine A , Hornick Jason L
Published: March 2013

Aims

The presence of a BRAF mutation is a strong marker for poor prognosis of colorectal carcinoma (CRC), and can be used as evidence of a sporadic mechanism of mismatch repair deficiency. BRAF mutation may also predict resistance to EGFR‐targeted therapy. A BRAF V600E‐specific antibody has recently become commercially available. The aim of this study was to determine whether immunohistochemistry can predict BRAF mutations in CRC.

Methods and results

Immunohistochemistry was performed on 52 genotyped CRC cases (17 BRAF mutant, 18 KRAS mutant, 17 BRAF/KRAS wild‐type) with monoclonal antibody VE1. Cytoplasmic staining was observed in 71% of BRAF V600E mutant tumours (moderate or strong staining in 50% of these cases). Weak cytoplasmic staining was observed in 17% of KRAS mutant tumours and 35% of wild‐type tumours. Non‐specific nuclear staining was common. The sensitivity and specificity of immunohistochemistry with VE1 for BRAF mutation were 71% and 74%, respectively; when only moderate or strong staining was considered to be positive, the specificity was 100%, but the sensitivity only 35%.

Conclusions

Immunohistochemistry with VE1 is not a useful surrogate for genotyping in CRC. Although moderate or strong cytoplasmic staining is specific for BRAF V600E mutations, this antibody is insufficiently sensitive to serve as an effective screening tool.
Structure‐Property Correlation in BaO‐TiO2‐B2O3 Glasses: Glass Stability, Optical, Hydrophobic, and Dielectric Properties
Authors: Paramesh Gadige , Varma Kalidindi B. R.
Published: April 2013

Glasses in the x(BaO‐TiO2)‐B2O3 (x = 0.25, 0.5, 0.75, and 1 mol.) system were fabricated via the conventional melt‐quenching technique. Thermal stability and glass‐forming ability as determined by differential thermal analysis (DTA) were found to increase with increasing BaO–TiO2 (BT) content. However, there was no noticeable change in the glass transition temperature (Tg). This was attributed to the active participation of TiO2 in the network formation especially at higher BT contents via the conversion of the TiO6 structural units into TiO4 units, which increased the connectivity and resulted in an increase in crystallization temperature. Dielectric and optical properties at room temperature were studied for all the glasses under investigation. Interestingly, these glasses were found to be hydrophobic. The results obtained were correlated with different structural units and their connectivity in the glasses.
Preimplantation genetic diagnosis, an alternative to conventional prenatal diagnosis of the hemoglobinopathies
Authors: Traeger‐Synodinos J.
Published: April 2013

Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) both represent highly important reproductive choices for couples with a high risk of transmitting a severe disease, such as a severe hemoglobinopathy. Conventional PND for hemoglobinopathies based on molecular analysis of trophoblast or amniocyte DNA has been applied for around 30 years, but the major disadvantages with this approach include ‘invasive’ fetal sampling, and the potential involvement of pregnancy termination when affected. In comparison, the major advantage of PGD over conventional PND is that it supports the initiation of unaffected pregnancies, avoiding the need to terminate affected pregnancies. However, it is a multistep technically demanding procedure requiring the close collaboration of experts from several fields. PGD is also limited by the need to involve assisted reproduction, even in couples without fertility problems. Furthermore, even for fertile couples, pregnancy rates rarely surpass 30–35%. Both PND and PGD have advantages and drawbacks. Before embarking on either procedure, couples should be carefully counseled by experts so that they can select the option most appropriate for them. Finally, whatever their choice, it is paramount that both prenatal and PGD be applied with the highest standards of clinical, laboratory, and ethical practice.
MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer
Authors: Tili Esmerina , Michaille Jean‐Jacques , Croce Carlo M.
Published: April 2013

It is now largely admitted that a pro‐inflammatory environment may curtail anti‐tumor immunity and favor cancer initiation and progression. The discovery that small non‐coding regulatory RNAs, namely microRNAs (miRNAs), regulate all aspects of cell proliferation, differentiation, and function has shed a new light on regulatory mechanisms linking inflammation and cancer. Thus, miRNAs such as miR‐21, miR‐125b, miR‐155, miR‐196, and miR‐210 that are critical for the immune response or hypoxia are often overexpressed in cancers and leukemias. Given the high number of their target transcripts, their deregulation may have a number of deleterious consequences, depending on the cellular context. In this review, we focus on how the factors encoded by transcripts targeted by these five miRNAs, be they transcription factors, tumor‐suppressors, or regulators of different signaling pathways, can deregulate the immune response and favor pro‐tumor immunity. Furthermore, we expose how the misdirected action of the main regulators of these miRNAs, such as nuclear factor κB (NF‐κB), activator protein‐1 (AP‐1), and signal transduction and activators of transcription (STAT) transcription factors, or AKT and transforming growth factor β (TGFβ) signaling pathways, can contribute to decrease anti‐tumor immunity and enhance cell proliferation and oncogenesis. We conclude by briefly discussing about how these discoveries may possibly lead to the development of new miRNA‐based cancer therapies.
Safety and tolerability of a 2009 trivalent inactivated split‐virion influenza vaccine in infants, children and adolescents
Authors: Lambert Stephen B. , Chuk Lai‐man R. , Nissen Michael D. , Nolan Terry M. , McVernon Jodie , Booy Robert , Heron Leon , Richmond Peter C. , Walls Tony , Marshall Helen S. , Reynolds Graham J. , Hartel Gunter F. , Hu Wilson , Lai Michael H.
Published: April 2013

Objective

To evaluate the safety of CSL's split‐virion inactivated trivalent 2009 Southern Hemisphere formulation influenza vaccine (TIV) in children.

Methods

We enrolled 1992 healthy children into three groups: Cohorts A, ≥6 months to <3 years; B, ≥3 years to <9 years; and C, ≥9 years to <18 years. Children received one or two doses of 0·25 ml (22·5 μg haemagglutinin) or 0·5 ml (45 μg) TIV, depending on age and prior vaccination history. We collected post‐vaccination solicited adverse event (AE) data (days 0–6), including fever (temperature: ≥37·5°C axilla, ≥38·0°C oral), unsolicited AEs (days 0–29) and serious AEs (SAEs) and new‐onset chronic illnesses (NOCIs; to day 180 after last vaccination).

Results

At least one solicited AE was reported by 80%/78%/78% of children in Cohorts A, B and C, respectively. Systemic AEs were more common among Cohort A (72% of participants), and local AEs were more common among Cohort C (71% of participants). Fever was more common in younger cohorts, in influenza vaccine‐naïve children (29% of Cohort A receiving their first dose), and following first compared with second doses. Severe fever following a first dose prevented 20 participants receiving their second scheduled vaccine dose. A 7‐month‐old participant had a single uncomplicated febrile convulsion on the day of vaccination.

Conclusions

Nearly 80% of subjects reported at least one solicited AE following immunization. Fever prevalence was highest in vaccine‐naïve Cohort A participants, similar to other paediatric studies using CSL vaccine. Further research to understand fever‐related AEs in children following CSL's TIV is recommended.
Favourable long‐term outcomes with brachytherapy‐based regimens in men ≤60 years with clinically localized prostate cancer
Authors: Kollmeier Marisa A. , Fidaleo Anthony , Pei Xin , Cohen Gil'ad , Zaider Marco , Mo Quincy , Cox Brett , Yamada Yoshiya , Zelefsky Michael J.
Published: April 2013

What's known on the subject? and What does the study add?

Brachytherapy (BT)‐based treatment for clinically localized prostate cancer is a well‐accepted treatment strategy; however, there is concern that long‐term outcomes and morbidity may not be acceptable in young patients (≤60 years).

We report our long‐term experience with BT in men aged ≤ 60 years with a minimum of 2 years of post‐treatment follow‐up. Our results show low treatment‐related morbidity and excellent long‐term outcomes with BT‐based treatment and suggest that such treatment should be offered to this patient population.

Objective

To report long‐term outcomes of men ≤60 years treated with brachytherapy (BT) for low‐ and intermediate‐risk prostate cancer.

Patients and Methods

Of 1655 patients treated with BT for clinically localized prostate cancer between January 1998 and May 2008 at Memorial Sloan‐Kettering Cancer Center, 236 patients with National Comprehensive Cancer Network low‐ (n = 178) or intermediate‐risk (n = 58) prostate cancer were ≤60 years old with a 3‐year minimum follow‐up, and represent the subjects of this report.

Brachytherapy was given either as monotherapy (n = 169) or with external beam radiation therapy (EBRT; n = 67). Forty‐four patients (19%) received neoadjuvant cytoreductive hormone therapy. The ‘nadir+2’ definition was used for prostate‐specific antigen (PSA) recurrence.

Common Terminology Criteria for Acute Events (CTCAE) v 3.0 was used to grade genitourinary (GU) and gastrointestinal (GI) toxicity. Potency was defined as the ability to obtain an erection suitable for intercourse or an International Index of Erectile Function score ≥ 22.

The Kaplan–Meier method and Cox regression were used for statistical analysis. The median follow‐up was 83 months.

Results

The 8‐year PSA relapse‐free survival (RFS), cancer‐specific and overall survival rates for the entire cohort were 96, 99 and 96%, respectively.

For patients with low‐risk disease, the 8‐year PSA RFS rate was 97% and for intermediate‐risk patients it was 94% (P = 0.34).

There was no difference in PSA RFS between BT alone and combined therapy (P = 0.17). Late grade ≥ 2 GU and GI toxicity was 14 and 3%, respectively.

Of 150 patients potent before treatment, 76 (51%) were potent at last follow‐up, with 50/76 (66%) using no medication.

There was no significant difference in post‐treatment potency between BT alone and BT with EBRT (P = 0.74).

Conclusions

Brachytherapy provides patients aged ≤ 60 years with low‐ and intermediate‐risk prostate cancer with excellent outcomes and has a low risk of significant long‐term GU or GI morbidity.

Erectile function is preserved in >50% of patients and the majority do not require erectile dysfunction medication.
Microwave Sintering: Fundamentals and Modeling
Authors: Rybakov Kirill I. , Olevsky Eugene A. , Krikun Ekaterina V.
Published: March 2013

This paper reviews the basic physical notions underlying microwave sintering and the theoretical and numerical models of the microwave sintering process. The propagation and absorption of electromagnetic waves in materials, and the distribution of electromagnetic field in cavity resonators that serve as applicators for microwave processing are discussed and the electromagnetic modeling of such applicators is reviewed. The microwave absorption properties of ceramic and metal powder materials and the methods of their description are addressed. Self‐consistent electromagnetic and thermal models that are capable of predicting the temperature distribution in the microwave‐heated materials and dynamic effects such as thermal runaway instabilities are reviewed. The multiphysics simulations that combine electromagnetic, thermal, and sintering models and result in predicting densification, shrinkage, and grain structure evolution are discussed in detail. The significance of microwave nonthermal effects in sintering is demonstrated based on the experimental results, and the models of such effects are reviewed.
Up‐regulation and activation of the P2Y2 nucleotide receptor mediate neurite extension in IL‐1β‐treated mouse primary cortical neurons
Authors: Peterson Troy S. , Thebeau Christina N. , Ajit Deepa , Camden Jean M. , Woods Lucas T. , Wood W. Gibson , Petris Michael J. , Sun Grace Y. , Erb Laurie , Weisman Gary A.
Published: March 2013

The pro‐inflammatory cytokine interleukin‐1β (IL‐1β), whose levels are elevated in the brain in Alzheimer's and other neurodegenerative diseases, has been shown to have both detrimental and beneficial effects on disease progression. In this article, we demonstrate that incubation of mouse primary cortical neurons (mPCNs) with IL‐1β increases the expression of the P2Y2 nucleotide receptor (P2Y2R) and that activation of the up‐regulated receptor with UTP, a relatively selective agonist of the P2Y2R, increases neurite outgrowth. Consistent with the accepted role of cofilin in the regulation of neurite extension, results indicate that incubation of IL‐1β‐treated mPCNs with UTP increases the phosphorylation of cofilin, a response absent in PCNs isolated from P2Y2R−/− mice. Other findings indicate that function‐blocking anti‐αvβ3/5 integrin antibodies prevent UTP‐induced cofilin activation in IL‐1β‐treated mPCNs, suggesting that established P2Y2R/αvβ3/5 interactions that promote G12‐dependent Rho activation lead to cofilin phosphorylation involved in neurite extension. Cofilin phosphorylation induced by UTP in IL‐1β‐treated mPCNs is also decreased by inhibitors of Ca2+/calmodulin‐dependent protein kinase II (CaMKII), suggesting a role for P2Y2R‐mediated and Gq‐dependent calcium mobilization in neurite outgrowth. Taken together, these studies indicate that up‐regulation of P2Y2Rs in mPCNs under pro‐inflammatory conditions can promote cofilin‐dependent neurite outgrowth, a neuroprotective response that may be a novel pharmacological target in the treatment of neurodegenerative diseases.
Clinical trial recruitment – a complex intervention?
Authors: Tramm Ralph , Daws Karen , Schadewaldt Verena
Published: April 2013

Aims and objectives

To discuss the evidence of poor recruitment rates in randomised clinical trials and relate this to existing recruitment methodology before a novel approach to recruitment is suggested.

Background

Recruitment is crucial to the success of research projects. Effective recruitment leads to effective retention, an increased pool of data and in‐time completion of projects. Robust evidence indicates that recruitment remains a challenge in many clinical trials.

Design

Discursive article.

Methods

The complexity of recruitment is mandated based on the findings from a literature review that summarises common threats to successful recruitment. Nursing theories and models that incorporate recruitment are critically reviewed before recruiting, and its planning is related to existing complex intervention methodology.

Conclusion

Threats to sufficient recruitment are inherent in the planning of studies, the recruiting process and triadic relationships between institutions, recruiter and participants. Existing nursing theories and models address important recruitment issues but do not account for all aspects that jeopardise sufficient recruitment. Hence, available frameworks for complex intervention planning and evaluation are useful to guide recruitment and its planning as an umbrella methodology.

Relevance to clinical practice

Using complex intervention methodology for recruitment and its planning enhances a nurse researcher's awareness of the challenges and pitfalls recruitment poses and may translate to improved recruitment rates and overall success of clinical trials.
The development and psychometric evaluation of the Chinese version of the maternal attachment inventory
Authors: Chen Chen‐Jung , Sung Huei‐chuan , Chen Yi‐Chang , Chang Ching‐Yuan , Lee Ming‐Shinn
Published: April 2013

Aims and objectives

To develop the Maternal Attachment Inventory (MAI) into Chinese and assess its psychometric properties.

Background

The MAI measures of maternal affectionate attachment. This scale displays the most appropriate indicators associated with attachment and has been widely adopted in different fields for measuring maternal–infant attachment.

Design

Cross‐sectional survey design.

Methods

The study was carried out in two clinics. From the accessible population of 507 samples, a simple random sampling method of selection was used to randomly choose 200 names of mothers at 4–8 months after delivery using a computer. One hundred and eighty‐one mothers agreed to participate in the study. The Chinese version of the MAI (CMAI) was developed in five stages: translation, review, back‐translation, a review by a panel of specialists and a pilot test. Regarding the reliability of the CMAI, a test of correlations between the subscales and the entire scale was performed consecutively. With respect to the validity of the MAI, exploratory factor analyses, a test of relationships between items and subscales, and an analysis of concurrent criterion‐related validity were conducted.

Results

The CMAI contains four factors in its structure. The CMAI and its subscales possess good internal consistency; the Cronbach's α coefficient was 0·94. In addition, the Pearson product‐moment correlation coefficient between the CMAI and the Maternal–Fetal Attachment Inventory (MFAI) and between the CMAI and the Maternal–Infant Attachment Inventory (MIAI) was 0·38 and 0·5, respectively. This suggests significant medium and high respective correlations between the CMAI and these two scales. One major limitation of this study is that participants were recruited from two clinics located in central Taiwan.

Conclusions

The CMAI possesses acceptable reliability and validity for use in measuring the levels of attachment and affectional ties between mothers and their infants.

Relevance to clinical practice

The CMAI provides further evidence of the applicability of the CMAI in clinical maternity care services.
Oral mucosal status and salivaryIgAlevels ofHIV‐infected children
Authors: Subramaniam Priya , Kumar Krishna
Published: March 2013

Background

PediatricHIVis a major world health problem, which is progressing at an alarming rate. Lesions in the mouth and in other tissues and organs (oral and systemic lesions) in pediatricHIVinfection are diverse and show differences in clinical presentation and severity from that of adults. Very little data exist for oral lesions in pediatric population in India. To assess oral mucosal status ofHIV‐infected children and to correlate it with their salivaryIgAlevels.

Methods

The study group consisted of 150HIV‐infected children aged 6–18 years. They were divided into two groups. Group 1: Children prior to anti‐retroviral therapy, Group 2: Children undergoing anti‐retroviral therapy (for not more than 3 years). Criteria given by Ramos‐Gomez for diagnosis of oral lesions commonly associated withHIVinfection in children were used to record the oral lesions. SalivaryIgAlevels were determined by enzyme‐linked immunosorbent assay. Data obtained were subjected to statistical analysis.

Results

There was a significant difference in mean secretoryIgA(SIgA) levels between the groups (P ≤ 0.05). All the children had one or more oral mucosal lesions, with angular cheilitis being the most common lesion. There was a significant inverse relation betweenSIgAlevels and individual oral mucosal lesions (P ≤ 0.05). The number of oral lesions was inversely related to theSIgAlevels.

Conclusion

Oral mucosal lesions were a significant feature ofHIV‐infected infection, particularly in children prior to the onset of anti‐retroviral therapy. All children showed lowSIgAlevels. Early recognition and management of oral conditions are important to improve the quality of life in these children.
Predictors of expressed emotion, burden and quality of life in relatives of Mexican patients with psychosis
Authors: Gómez‐de‐Regil L. , Kwapil T. R. , Barrantes‐Vidal N.
Published: April 2013

Accessible summary

Families play an important role in the recovery of mental health patients providing daily informal care. Without support from and an alliance with clinical professionals, family members may feel overwhelmed by the challenge of having a relative with a mental disorder.

The study explores whether the relatives' own feelings of burden, expressed emotion and quality of life can be affected not only by the symptoms of their ill relative but also by how relatives themselves perceive the illness and how psychologically distressed they feel. From a public psychiatric hospital located in Mexico, 65 patients with psychosis were interviewed along with their closest caregiver.

Feeling psychologically distressed increases relatives' burden, expressed emotion and negatively affects their quality of life. Regardless of the patient's mental health status, perceiving the illness as chronic increases relatives' burden. Moreover, when relatives believe that they, rather than treatment or the patient, control or influence the illness, they feel more burden, and their quality of life is poorer. The quality of life of the relatives is also disrupted by their perception of illness as affecting their own lives as well as patients'.

Results underscore the relatives' need of support to overcome their own distress and concerns about the illness, for the psychological well‐being of both patients and relatives.

Expressed emotion, burden and quality of life of relatives received attention because of the increasing interest in predicting and preventing relapse in psychotic patients; but they have subsequently acquired interest of their own as important aspects of families' psychological well‐being. The study explores whether the psychological distress and illness perception of a sample of relatives of Mexican patients with psychosis can predict their levels of expressed emotion, burden and quality of life above patients' clinical and functional status. Sixty‐five patient–relative dyads were interviewed. Relatives self‐reported on expressed emotion, burden, quality of life, psychological distress and illness perception. Patients' clinical and functional status was rated by an interviewer. Pearson correlations and hierarchical multiple linear regressions were used for statistical analyses. Patients' functional status and relatives' psychological distress were significantly associated with expressed emotion, burden and quality of life. Patients' clinical status and relatives' illness perception were most strongly related to expressed emotion and burden. Relatives' psychological distress and illness perception dimensions predicted both burden and quality of life, over and above patients' clinical and functional status. Results underscore the relatives' need of support to overcome their own distress and concerns about the illness, for the psychological well‐being of both patients and relatives.
Impact of Urodynamic Learning on the Management of Benign Prostatic Hyperplasia Issue on Young and Senior Urologists and Reasons to Attend a Voiding Dysfunction Course
Authors: RODRIGUES Paulo , HERING Flávio , CAMPAGNARI João Carlos
Published: April 2013

Objectives

The aims of this study were to compare the impact of urodynamic training on the young urologists after fellowship training as well as on senior urologists who attend regular courses on the management of benign prostatic hyperplasia (BPH) and their capacity to do and interpret urodynamic studies.

Methods

Sixty‐four consecutive young urologists admitted to fellowship program on voiding dysfunctions and 110 senior urologists attending to periodical meetings were interviewed before and after the 3‐day‐courses regarding their ability to set, interpret and do urodynamic studies. They were also questioned on the reasons that led them to attend the courses and how they use the new concepts to manage BPH. A rank of the used parameters to indicate transurethral resection of the prostate (TURP) in BPH patients were scored before and after the course.

Results

Fellowship and senior urologists mainly attended the course because of lack of confidence and belief that this urological issue is too important to be disregarded. A significant portion of both groups do not trust third‐party examiners. More than 90% of the urologists acquired confidence in interpreting, setting and were able to do the exam after the course. The majority of both groups believed urodynamic study was essential to manage BPH, disregarding volume as the main reason to operate on patients. Many outdated parameters became less important on the decision to operate.

Conclusions

Doctors exposed to intensive or long urodynamic training dramatically changed their perceptions on the utility of this tool and became more attentive it.
Predicting positive food challenges in children sensitised to peanuts/tree nuts
Authors: Ludman Sian , Ballabeni Pierluigi , Eigenmann Philippe A. , Wassenberg Jacqueline
Published: April 2013

Background

Children with atopic diseases in early life are frequently found with positive IgE tests to peanuts/tree nuts without a history of previous ingestion. We aimed to identify risk factors for reactions to nuts at first introduction.

Methods

A retrospective case‐note and database analysis was performed. Recruitment criteria were: patients aged 3–16 yr who had a standardized food challenge to peanut and/or tree nuts due to sensitisation to the peanut/tree nut (positive spIgE or SPT) without previous consumption. A detailed assessment was performed of factors relating to food challenge outcome with univariate and multivariate logistic regression analysis.

Results

There were 98 food challenges (47 peanut, 51 tree nut) with 29 positive, 67 negative and 2 inconclusive outcomes. A positive maternal history of allergy and a specific IgE >5 kU/l were strongly associated with a significantly increased risk of a positive food challenge (OR 3.73; 95% CI 1.31–10.59; p = 0.013 and OR 3.35; 95% CI 1.23–9.11; p = 0.007, respectively). Adjusting for age, a three year‐old with these criteria has a 67% probability of a positive challenge. There was no significant association between types of peanut/tree nut, other food allergies, atopic conditions or severity of previous food reactions and positive challenges.

Conclusions

We have demonstrated an association between the presence of maternal atopic history and a specific IgE >5 kU/l, with a significant increase in the likelihood of a positive food challenge. Although requiring further prospective validation these easily identifiable components should be considered when deciding the need for a challenge.
New insights into Chlamydomonas reinhardtii hydrogen production processes by combined microarray/RNA‐seq transcriptomics
Authors: Toepel Jörg , Illmer‐Kephalides Maike , Jaenicke Sebastian , Straube Jasmin , May Patrick , Goesmann Alexander , Kruse Olaf
Published: April 2013

Hydrogen production with Chlamydomonas reinhardtii induced by sulphur starvation is a multiphase process while the cell internal metabolism is completely remodelled. The first cellular response is characterized by induction of genes with regulatory functions, followed by a total remodelling of the metabolism to provide reduction equivalents for cellular processes. We were able to characterize all major processes that provide energy and reduction equivalents during hydrogen production. Furthermore, C. reinhardtii showed a strong transcript increase for gene models responsible for stress response and detoxification of oxygen radicals. Finally, we were able to determine potential bottlenecks and target genes for manipulation to increase hydrogen production or to prolong the hydrogen production phase. The investigation of transcriptomic changes during the time course of hydrogen production in C. reinhardtii with microarrays and RNA‐seq revealed new insights into the regulation and remodelling of the cell internal metabolism. Both methods showed a good correlation. The microarray platform can be used as a reliable standard tool for routine gene expression analysis. RNA‐seq additionally allowed a detailed time‐dependent study of gene expression and determination of new genes involved in the hydrogen production process.
Antioxidant Status and Oxidative Stress in Patients with Chronic ITP
Authors: Jin C.‐Q. , Dong H.‐X. , Cheng P.‐P. , Zhou J.‐W. , Zheng B.‐Y. , Liu F.
Published: March 2013

The aim of this study was to establish the antioxidant status and oxidative stress in adult patients with chronic idiopathic thrombocytopenic purpura (ITP). Eighty‐four patients diagnosed with chronic ITP were studied. Fifty‐eight age‐matched healthy subjects were selected as controls. Serum nitrogen monoxide ( NO), oxidized glutathione (GSSG), malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase(SOD), hydrogen peroxide enzyme (CAT), glutathione peroxidase (GSH‐Px), glutathione (GSH) were evaluated by enzyme‐linked immunosorbent assay (ELISA). It was found that serum SOD, CAT, GSH‐Px, GSH, TAS levels were significantly lower in patients with chronic ITP than controls (all P < 0.05), while serum NO, GSSG, MDA, TOS values were significantly higher (P < 0.05). The number of platelet showed a negative correlation with NO, GSSG, MDA, TOS, respectively,while platelet number showed a positive correlation with SOD, CAT, GSH‐Px, GSH, TAS. These findings suggested that oxidants were increased and antioxidants were decreased in patients with chronic ITP, these may be prominent factors in destructing the platelet membrane. The scavenging of oxygen radical provides a theoretical basis for the treatment of ITP patients.
Sterols are required for cell‐fate commitment and maintenance of the stomatal lineage in Arabidopsis
Authors: Qian Pingping , Han Bing , Forestier Edith , Hu Zhihong , Gao Na , Lu Wenwen , Schaller Hubert , Li Jia , Hou Suiwen
Published: March 2013

Asymmetric cell division is important for regulating cell proliferation and fate determination during stomatal development in plants. Although genes that control asymmetric division and cell differentiation in stomatal development have been reported, regulators controlling the process from asymmetric division to cell differentiation remain poorly understood. Here, we report a weak allele (fk–J3158) of the Arabidopsis sterol C–14 reductase gene FACKEL (FK) that shows clusters of small cells and stomata in leaf epidermis, a common phenomenon that is often seen in mutants defective in stomatal asymmetric division. Interestingly, the physical asymmetry of these divisions appeared to be intact in fk mutants, but the cell‐fate asymmetry was greatly disturbed, suggesting that the FK pathway links these two crucial events in the process of asymmetric division. Sterol profile analysis revealed that the fk–J3158 mutation blocked downstream sterol production. Further investigation indicated that cyclopropylsterol isomerase1 (cpi1), sterol 14α–demethylase (cyp51A2) and hydra1 (hyd1) mutants, corresponding to enzymes in the same branch of the sterol biosynthetic pathway, displayed defective stomatal development phenotypes, similar to those observed for fk. Fenpropimorph, an inhibitor of the FK sterol C–14 reductase in Arabidopsis, also caused these abnormal small‐cell and stomata phenotypes in wild‐type leaves. Genetic experiments demonstrated that sterol biosynthesis is required for correct stomatal patterning, probably through an additional signaling pathway that has yet to be defined. Detailed analyses of time‐lapse cell division patterns, stomatal precursor cell division markers and DNA ploidy suggest that sterols are required to properly restrict cell proliferation, asymmetric fate specification, cell‐fate commitment and maintenance in the stomatal lineage cells. These events occur after physical asymmetric division of stomatal precursor cells.
MALDI mass spectrometry‐assisted molecular imaging of metabolites during nitrogen fixation in the Medicago truncatula–Sinorhizobium meliloti symbiosis
Authors: Ye Hui , Gemperline Erin , Venkateshwaran Muthusubramanian , Chen Ruibing , Delaux Pierre‐Marc , Howes‐Podoll Maegen , Ané Jean‐Michel , Li Lingjun
Published: March 2013

Symbiotic associations between leguminous plants and nitrogen‐fixing rhizobia culminate in the formation of specialized organs called root nodules, in which the rhizobia fix atmospheric nitrogen and transfer it to the plant. Efficient biological nitrogen fixation depends on metabolites produced by and exchanged between both partners. The Medicago truncatula–Sinorhizobium meliloti association is an excellent model for dissecting this nitrogen‐fixing symbiosis because of the availability of genetic information for both symbiotic partners. Here, we employed a powerful imaging technique – matrix‐assisted laser desorption/ionization (MALDI)/mass spectrometric imaging (MSI) – to study metabolite distribution in roots and root nodules of M. truncatula during nitrogen fixation. The combination of an efficient, novel MALDI matrix [1,8–bis(dimethyl‐amino) naphthalene, DMAN] with a conventional matrix 2,5–dihydroxybenzoic acid (DHB) allowed detection of a large array of organic acids, amino acids, sugars, lipids, flavonoids and their conjugates with improved coverage. Ion density maps of representative metabolites are presented and correlated with the nitrogen fixation process. We demonstrate differences in metabolite distribution between roots and nodules, and also between fixing and non‐fixing nodules produced by plant and bacterial mutants. Our study highlights the benefits of using MSI for detecting differences in metabolite distributions in plant biology.
High‐throughput simultaneous genotyping of human platelet antigen‐1 to ‐16 by using suspension array
Authors: An Qun‐Xing , Li Cui‐Ying , Xu Li‐Juan , Zhang Xian‐Qing , Bai Yan‐Jun , Shao Zhong‐Jun , Zhang Wei
Published: April 2013

Background

Comprehensive and accurate detection of human platelet antigens (HPAs) plays a significant role in diagnosis and prevention of the platelet (PLT) alloimmune syndromes and ensuring clinical safety of patients undergoing PLT transfusion. The majority of the available methods are incapable of performing high‐throughput simultaneous detection of HPA‐1 to ‐16, and the accuracy of many methods needs to be further enhanced.

Study Design and Methods

We have developed a new HPA‐genotyping method for simultaneous detection of HPA‐1 to ‐16 based on suspension array technology. A total of 216 samples from Chinese Han donors in Xi'an were genotyped using the developed method, and all the samples again were genotyped using polymerase chain reaction (PCR) sequence‐based typing (PCR‐SBT), which is considered the gold standard.

Results

All 216 samples were successfully genotyped for HPA‐1 to ‐16 using both our method and PCR‐SBT. Results showed that the genotype and allele frequencies obtained using our method were fully consistent with those obtained using PCR‐SBT.

Conclusion

Our method provides accurate, high‐throughput, and simultaneous genotyping of HPA‐1 to ‐16 and will serve as the foundation for large‐scale clinical genotyping of HPAs and for the establishment of an HPA‐typed PLT donor registry.