bluuebunny/crossref_metadata_2025 huggingface dataset:
Pumilio facilitates miRNA regulation of the E2F3 oncogene
Authors: Miles Wayne O. , Tschöp Katrin , Herr Anabel , Ji Jun-Yuan , Dyson Nicholas J.
Published: February 2012

E2F transcription factors are important regulators of cell proliferation and are frequently dysregulated in human malignancies. To identify novel regulators of E2F function, we used Drosophila as a model system to screen for mutations that modify phenotypes caused by reduced levels of dE2F1. This screen identified components of the Pumilio translational repressor complex (Pumilio, Nanos, and Brain tumor) as suppressors of dE2F1-RNAi phenotypes. Subsequent experiments provided evidence that Pumilio complexes repress dE2F1 levels and that this mechanism of post-transcriptional regulation is conserved in human cells. The human Pumilio homologs Pum 1 and Pum 2 repress the translation of E2F3 by binding to the E2F3 3′ untranslated region (UTR) and also enhance the activity of multiple E2F3 targeting microRNAs (miRNAs). E2F3 is an oncogene with strong proliferative potential and is regularly dysregulated or overexpressed in cancer. Interestingly, Pumilio/miRNA-mediated regulation of E2F3 is circumvented in cancer cells in several different ways. Bladder carcinomas selectively down-regulate miRNAs that cooperate with Pumilio to target E2F3, and multiple tumor cell lines shorten the 3′ end of the E2F3 mRNA, removing the Pumilio regulatory elements. These studies suggest that Pumilio–miRNA repression of E2F3 translation provides an important level of E2F regulation that is frequently abrogated in cancer cells.
Sumoylation of transcription factor Gcn4 facilitates its Srb10-mediated clearance from promoters in yeast
Authors: Rosonina Emanuel , Duncan Sarah M. , Manley James L.
Published: February 2012

The small ubiquitin-related modifier (SUMO) is a conserved factor that post-translationally regulates proteins involved in many cellular processes, including gene transcription. We previously demonstrated that promoter-bound factors become sumoylated during activation of inducible genes in yeast, but the identity of these factors, and the role of sumoylation in their function, was unknown. Here we show that the transcriptional activator Gcn4 is sumoylated on two specific lysine residues and in a manner that depends on its ability to bind DNA, indicating that sumoylation occurs after Gcn4 binding to target promoters. Importantly, this functions to facilitate the subsequent removal of the activator from these promoters after recruitment of RNA polymerase II, which can prevent inappropriate transcription of target genes. Furthermore, we show that clearance of sumoylated Gcn4 requires the protein kinase and Mediator complex subunit Srb10, linking activator removal with target gene transcription. Our study demonstrates an unexpected role for protein sumoylation in the process of transcriptional activation.
Assessment of von Willebrand disease as a risk factor for primary postpartum haemorrhage
Authors: CHEE Y. L. , TOWNEND J. , CROWTHER M. , SMITH N. , WATSON H. G.
Published: February 2012

Summary.  It is not clear whether von Willebrand disease (VWD) is associated with an increased risk of postpartum haemorrhage (PPH). We assessed the effect of VWD on PPH in a case‐control study. Logistic regression was used to test for differences in the odds of PPH in deliveries to women with and without VWD, before and after adjustment for known risk factors. A total of 62 deliveries in 33 women with VWD were compared with controls matched for age, year of delivery and parity. Primary PPH was observed in 12/62 (19.4%) deliveries in women with VWD and 16/124 (12.9%) controls. The unadjusted odds ratio (OR) for VWD as a risk factor for PPH was 1.62 (95% CI 0.75–3.49, P = 0.22). After adjustment for other risk factors for PPH, the OR for VWD as a risk factor for PPH was 1.31 (95% CI 0.48–3.60, P = 0.60). PPH was observed in 7/24 (29%) deliveries in women known prepregnancy to have VWD. The unadjusted odds for VWD as a risk factor for PPH in this group was significantly greater than the control group (OR 2.78 (95% CI 1.03–7.49) P = 0.043) and remained significant after adjusting for other significant risk factors (OR 3.41 (95% CI 1.07–10.9) P = 0.038). VWD in itself may not be a significant risk factor for PPH, however, women known to have VWD predelivery may represent an at risk sub‐group.
Current prescription of prophylactic factor infusions and perceived adherence for children and adolescents with haemophilia: a survey of haemophilia healthcare professionals in the United States
Authors: THORNBURG C. D. , CARPENTER S. , ZAPPA S. , MUNN J. , LEISSINGER C.
Published: February 2012

Summary.  The primary goal of prophylaxis in patients with severe haemophilia is to convert the phenotype from severe to moderate and to prevent the development of chronic arthropathy. Prior studies have demonstrated that prophylaxis decreases episodes of joint bleeds and chronic arthropathy. Effectiveness depends on prescription of prophylaxis and adherence to the prescribed regimen. The aim of this study was to determine if prescription of prophylaxis for children with haemophilia and perceptions of adherence to prophylaxis have changed since publication of the Joint Outcome Study (JOS). A questionnaire was sent, in electronic and written formats, to health professionals who provide care to children with haemophilia at US haemophilia treatment centres (HTCs). The response rate was 56 of 128 (44%) of the targeted HTCs. There were a few missing data and denominators are provided. All responses agreed with the results of the JOS and 30/55 (55%) reported the JOS increased their prescription of prophylaxis. Nineteen of 56 (34%) physicians or HTC staff reported that they had not prescribed prophylaxis within the last year due to concerns about adherence, and 19/56 (34%) reported they had stopped prophylaxis due to concerns about adherence within the last year. Predicted adherence decreased with increasing age. Prescription of prophylaxis appears to be increasing since publication of the JOS. Strategies to improve adherence may increase the likelihood of physician prescription of prophylaxis and make prophylaxis easier to implement for individual patients, thereby improving the clinical outcome of children and adults with haemophilia.
Learning to live with diabetes – integrating an illness or objectifying a disease
Authors: Kneck Åsa , Klang Birgitta , Fagerberg Ingegerd
Published: February 2012

kneck å., klang b. & fagerberg i. (2012) Learning to live with diabetes – integrating an illness or objectifying a disease. Journal of Advanced Nursing68(11), 2486–2495.

Aim.  This paper is a report of a study of illuminating the meaning of ‘learning to live with diabetes’ 3 years after being diagnosed.

Background.  A changed situation, for example, in relation to living with diabetes, raises a need to understand. How time for experience contributes to this learning process for people living with diabetes is not yet well understood. It would therefore seem valuable to ask people, who have had diabetes over a similar length of time, to narrate their experience in relation to daily life situations in order to understand better how learning is established.

Design.  The study has a qualitative design.

Methods.  A life world approach was used, with interviews being conducted with 13 people who had been diagnosed with diabetes 3 years earlier. Data were collected in 2007, and analyses were conducted using a phenomenological‐hermeneutic method.

Findings.  How a person experiences the physical body was found to be crucial in the learning process. If the body with its signals is understood it can be a tool for experiencing and understanding the world and oneself. Feeling insecure about one’s own needs, and not trusting or understanding bodily signs, made participants dependent on others to make decisions for them.

Conclusion.  This study showed that duration of illness was ‘not’ of importance for the understanding of living with diabetes. Living with diabetes 3 years after being diagnosed meant to experience both an overall balance in one’s existence and a daily struggle.
Herbivore pressure on goldenrod (Solidago altissima L., Asteraceae): its effects on herbivore resistance and vegetative reproduction
Authors: Bode Robert F. , Kessler André
Published: February 2012

1. Ecological and physiological costs of resistance to herbivory are core concepts in the study of plant–insect interactions, but identifying them remains challenging. These costs are most obvious when trade‐offs in resource allocation occur between different growth and resistance traits.

2. We used plant genotypes collected from long‐term herbivore exclusion plots and from plots with natural herbivory. We evaluated putative trade‐offs between resistance to two different herbivore species (the larvae of the beetle Trirhabda virgata and the moth Spodoptera exigua), and between resistance and growth as a potential outcome of differential natural selection.

3. We hypothesized that long‐term exclusion of herbivores would result in differential natural selection on plant resistance traits that are expressed by marked differences in mean resistance between plants from populations with and without herbivores. The results supported this hypothesis. Genotypes from herbivore exclusion plots were less resistant to the more common herbivore in the system, T. virgata, than genotypes from control plots. In contrast, the genotypes from the two herbivory regimes were equally resistant to the rarer S. exigua caterpillars. As a consequence, resistance to one herbivore species did not correlate with resistance to another, suggesting independent evolution of resistance to multiple herbivores.

4. Plant growth correlated positively with resistance to Trirhabda, but not to Spodoptera, and only in plants from herbivore exclusion plots, leading us to reject the hypothesis of a growth resistance trade‐off.

5. Synthesis. Our results suggest that correlations between growth and resistance are context dependent and may only be apparent in populations relieved from certain natural pressures, such as in natural populations relieved from natural selection by herbivores.
The Arabidopsis RING‐type E3 ligase XBAT32 mediates the proteasomal degradation of the ethylene biosynthetic enzyme, 1‐aminocyclopropane‐1‐carboxylate synthase 7
Authors: Lyzenga Wendy J. , Booth Judith K. , Stone Sophia L.
Published: February 2012

E3 ubiquitin ligases select specific proteins for ubiquitin conjugation, and the modified proteins are commonly degraded through the 26S proteasome. XBAT32 is a RING‐type E3 ligase involved in maintaining appropriate levels of ethylene. Previous work has suggested that XBAT32 modulates ethylene production by ubiquitinating two ethylene biosynthesis enzymes, ACS4 (type‐II isoform) and ACS7 (type‐III isoform). In Arabidopsis, conserved sequences within the C‐terminal tail of type‐I and ‐II 1‐aminocyclopropane‐1‐carboxylate (ACC) synthase (ACS) isoforms influence ubiquitin‐dependent proteolysis. ACS7, the sole Arabidopsis type‐III ACS, contains a truncated C‐terminal tail that lacks all known regulatory sequences, which suggests that this isoform may not be subject to ubiquitin‐mediated proteasomal degradation. Here we demonstrate in planta that ACS7 is turned over in a 26S proteasome‐dependent manner and that degradation of ACS7 requires the E3 ligase XBAT32. Furthermore, the ethylene‐related phenotypes that result from overexpression of ACS7 in wild‐type plants are greatly exaggerated in xbat32‐1, suggesting that XBAT32 is required to attenuate the effect of overexpression of ACS7. This observation is consistent with a role for XBAT32 in the ubiquitin‐mediated degradation of ACS7. The dark‐grown phenotype of xbat32‐1 seedlings overexpressing ACS7 can be effectively rescued by aminoethoxyvinylglycine, an inhibitor of ACS activity. The degradation rate of ACS4 is also significantly slower in the absence of XBAT32, further implicating XBAT32 in the ubiquitin‐mediated degradation of ACS4. Altogether, these results demonstrate that XBAT32 targets ethylene biosynthetic enzymes for proteasomal degradation to maintain appropriate levels of hormone production.
True integrated weed management
Authors: YOUNG S L
Published: February 2012

Young SL (2012) True Integrated Weed Management. Weed Research 52, 107–111.

Using the simplest of definitions, integrated weed management has been described as ‘putting components [of weed control] together, not taking them apart’. Yet, weed science has stopped at the ‘field edge’ in assembling the components into a truly integrated approach. What is keeping weed scientists from developing real integrated weed control regardless of space and time? The answer to this question lies with our colleagues in the engineering and computer science fields, who have made significant advances in developing automated machinery for real‐time detection and control of weeds in cropping systems. By using the latest technologies that can quickly identify weeds and react with precisely targeted applications, conceptually, weed control tools could be integrated for use at anytime and at any point in a field. This paper provides justification for using a single platform in the field that can instantaneously assess individual weeds and determine the most appropriate control method, simultaneously. In addition, I have modified an existing concept design to show the potential for a highly responsive weed management system that can transcend spatiotemporal restrictions and within‐field variability.
Development and comorbidity of eczema, asthma and rhinitis to age 12 – data from the BAMSE birth cohort
Authors: Ballardini N. , Kull I. , Lind T. , Hallner E. , Almqvist C. , Östblom E. , Melén E. , Pershagen G. , Lilja G. , Bergström A. , Wickman M.
Published: February 2012

Background

Allergy‐related diseases are a public health issue, but knowledge on development and comorbidity among children is scarce. The aim was to study the development of eczema, asthma and rhinitis in relation to sex and parental allergy, in a population‐based cohort, during childhood.

Methods

At 1, 2, 4, 8 and 12 years, parental questionnaires were used to obtain data on allergy‐related diseases. Complete data for all five follow‐up occasions were available from 2916 children. Odds ratios for the risk of any allergy‐related disease in relation to heredity and sex were calculated using generalized estimating equations.

Results

At 12 years, 58% of the children had had eczema, asthma and/or rhinitis at some time. Disease turnover was high for all three diseases throughout the study. Comorbidity increased with age, and at 12 years, 7.5% of all the children were affected by at least two allergy‐related diseases. Parental allergy was associated with increased comorbidity and more persistent disease and increased the risk of having any allergy‐related disease (adjusted OR 1.76; 95% CI 1.57–1.97) up to 12 years. Male sex was associated with an increased risk throughout childhood. Boys and girls did not differ in disease persistence, and for comorbidity, the differences were minor.

Conclusions

Allergy‐related diseases may affect a majority of children. Eczema, asthma and rhinitis develop dynamically throughout childhood, and allergic comorbidity is common. These findings indicate that allergy‐related diseases should be neither seen nor studied as isolated entities.
Natural genetic variation in the expression regulation of the chloroplast antioxidant system among Arabidopsis thaliana accessions
Authors: Juszczak Ilona , Rudnik Radoslaw , Pietzenuk Björn , Baier Margarete
Published: February 2012

Photosynthesis is the predominant source of reactive oxygen species in light. In order to prevent the negative influence of reactive oxygen species (ROS) on cell functionality, chloroplasts have evolved a highly efficient antioxidant protection system. Here, we present the first study on natural variation in this system. Comparison of temperature and developmental responses in seven accessions of Arabidopsis thaliana from northern habitats showed that the regulation is widely genetically manifested, but hardly correlates with geographic parameters. Transcript, polysomal RNA (pRNA) and protein data showed that the ecotypes use different strategies to adjust the chloroplast antioxidative defense system, either by regulating transcript abundance or initiation of translation. Comparison of mRNA and pRNA levels showed that Col‐0 invests more into transcript accumulation, while Van‐0, WS and C24 regulates the chloroplast antioxidant protection system more on the level of pRNA. Nevertheless, both strategies of regulation led to the expression of chloroplast antioxidant enzymes at sufficient level to efficiently protect plants from ROS accumulation in Col‐0, WS, C24 and Van‐0. On the contrary, Cvi‐0, Ms‐0 and Kas‐1 accumulated high amounts of ROS. The expression of copper/zinc superoxide dismutase (Csd2), ascorbate peroxidases and 2‐Cys peroxiredoxins was higher in Cvi‐0 on the transcriptional level, while Csd2, peroxiredoxin Q, type II peroxiredoxin E and glutathione peroxidase 1 were induced in Ms‐0 on the mRNA level. Similar to Kas‐1, in which mRNA levels were less than or similar to Col‐0 gene, specific support for translation was observed in Ms‐0, showing that the ecotypes use different strategies to adjust the antioxidant system.
Continuous interscalene block: the good, the bad and the refined spread
Authors: IP V. H. Y. , TSUI B. C. H.
Published: February 2012

Continuous interscalene block is popular for shoulder surgery, but there are several challenges when performing this continuous block. The interscalene catheter is susceptible to incidental dislodgement and migration due to movement of the head and neck. Another important consideration is phrenic nerve involvement; the phrenic nerve is susceptible to being incidentally anaesthetised with local anaesthetic during interscalene block, owing to its close proximity to the interscalene groove. We present two cases: firstly, a case demonstrating an interscalene catheter insertion approach that provides an effective spread of local anaesthetic perineurally within the interscalene groove, with the additional benefit of preventing catheter dislodgement. Secondly, we present a case in which ultrasound‐guided interscalene catheter insertion resulted in phrenic nerve palsy in an asthmatic patient, where dilution or ‘wash‐off’ of local anaesthetic with normal saline and repositioning of the catheter under ultrasound guidance resulted in rapid recovery of respiratory function and adequate pain control.
A cost analysis of reusable and disposable flexible optical scopes for intubation
Authors: TVEDE M. F. , KRISTENSEN M. S. , NYHUS‐ANDREASEN M.
Published: February 2012

Background

Intubation using a flexible optical scope (FOS) is a cornerstone technique for managing the predicted and unpredicted difficult airway. The term FOS covers both fibre‐optic scopes and videoscopes. The total costs of using flexible scopes for intubation are unknown. The recent introduction of a disposable flexible scope for intubation merits closer scrutiny of the total costs associated with both modalities.

Methods

The costs incurred during intubations using FOSs at a large anaesthesia department were identified, and a series of intubations using a disposable scope were analyzed for comparison. Recognized health‐economic methodology was applied.

Results

During a 1‐year period, 360 FOS intubations were performed. In this clinical setting, the average cost of an intubation using a reusable FOS was €177.7. When using the disposable Ambu® aScope (Ambu A/S, Ballerup, Denmark), the cost was €204.4. The break‐even point, i.e. the number of intubations per month where the cost of using disposable and non‐disposable equipment is identical, was 22.5/month. A subgroup analysis looking solely at intubations performed with flexible videoscopes revealed that the cost per intubation was equal for disposable and reusable videoscopes.

Conclusion

At our institution, the total cost of an intubation is greater when using disposable compared with reusable equipment (€204.4 vs. €177.7). If video equipment with an external monitor is considered mandatory, the expenses are of equal magnitude. The cost analysis is particularly sensitive to the actual number of flexible optic intubations performed; with fewer intubations, the total cost will begin to favour disposable equipment.
Warfarin‐induced calciphylaxis successfully treated with sodium thiosulphate
Authors: Hafiji Juber , Deegan Patrick , Brais Rebecca , Norris Paul
Published: February 2012

Calciphylaxis is a rare life‐threatening form of skin necrosis. Although traditionally observed in patients with end‐stage renal disease and/or hyperparathyroidism, calciphylaxis has also been reported to occur in ‘non‐traditional’ patients with normal renal and parathyroid function. We report a case of warfarin‐induced calciphylaxis treated successfully with sodium thiosulphate and discuss the role of Vitamin K2 as a potential therapeutic option in the management of warfarin‐induced calciphylaxis.
The management of toxic epidermal necrolysis
Authors: Fernando Suran L
Published: February 2012

The mortality rate of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is high; approximately 5% for SJS and 25% for TEN. It is therefore vital for the treating physician to recognise SJS and TEN promptly through the identification of these diseases' characteristic clinical features so that the offending drug is promptly withdrawn, supportive therapy is administered and adjunctive therapies are considered. Supportive therapy addressing the manifestations and complications of acute skin failure include monitoring the fluid – electrolyte balance and providing enteral or parenteral nutrition, wound care and treatment of sepsis. In addition, supportive care of the affected mucosal surfaces is required through the use of aggressive ocular lubrication, topical corticosteroids, hygienic mouthwashes and oral anaesthetics, together with monitoring for urinary retention. There is sufficient evidence for the use of intravenous immune globulin in the acute management of SJS/TEN provided an adequate dose of 2–3 g/kg is administered. Cyclosporine appears to also be an effective agent although randomised control studies are required to demonstrate its benefit and establish the dose, duration of therapy and safety profile. The role of corticosteroids is currently under revision. Some earlier studies have shown a lack of efficacy or increased mortality in their use but the use of high doses early in the course of disease may actually reduce morbidity and mortality. The role of plasmapheresis, anti‐tumour necrosis factor (TNF) biologics and N‐acetylcysteine is promising but further studies are required to elucidate their benefit. Preventative strategies such as pharmacogenetic screening needs to be strongly considered, with the provision of cost‐effective assays with a rapid turn‐around time.
Development of Self‐Efficacy Questionnaire for Chinese Family Caregivers
Authors: Zhang Shu‐Ying , Edwards Helen , Yates Patsy , Ruth Elder , Guo Qi Hao
Published: February 2012

The purpose of this study was to develop a Self‐Efficacy Questionnaire for Chinese Family Caregivers. Semi‐structured interviews with 10 family caregivers of people with dementia were conducted to explore how Chinese caregivers manage caregiving and what difficulties they face. The findings of the study assisted in the development of the instrument. Five categories of caregiver behaviours were identified from the qualitative data: gathering information about treatment, symptoms, and health care; obtaining support; responding to behaviour disturbances; managing household, personal, and medical care; and managing distress associated with caregiving. The challenges of caregiving were also identified, including deterioration of care recipients, particularly their behaviour disturbances, a shortage of supportive resources, stigmatization of dementia among the general population, as well as increased distress and decreased social activities due to increased care demand. The findings were used to develop the Self‐Efficacy Questionnaire for Chinese Family Caregivers, and 35 items comprising five subscales (representing the above five categories of caregiver behaviour) were generated.
Self‐harm and attempted suicide within inpatient psychiatric services: A review of the Literature
Authors: James Karen , Stewart Duncan , Bowers Len
Published: February 2012

Self harm is a major public health concern, yet there are considerable challenges in providing support for those who self harm within psychiatric inpatient services. This paper presents the first review of research into self harm within inpatient settings. Searches of the main electronic databases were conducted using key words for self harm and inpatient care. There was substantial variation in the rates of self‐harm and attempted suicide between studies, but rates were highest on forensic wards. There was no evidence of differences in prevalence of self‐harm between men and women; women, however, were at increased risk of attempting suicide. People were more likely to self‐harm in private areas of the ward and in the evening hours, and often self‐harmed in response to psychological distress, or elements of nursing care that restricted their freedom. Wards used a variety of strategies to prevent self‐harm; however, there is little research into their effectiveness.
Acute renal failure induced by disseminated intravascular coagulopathy in a patient with adenomyosis
Authors: Yoo Heon Jong , Chang Dong Suk , Lee Ki Hwan
Published: February 2012

Disseminated intravascular coagulation is most frequently associated with obstetric catastrophes, metastatic malignancy, massive trauma and bacterial sepsis, but relatively rarely related to benign tumors. We report on disseminated intravascular coagulopathy in a patient with significant adenomyosis and menometrorrhagia. An extremely rare case, disseminated intravascular coagulopathy developed in this benign case and was successfully treated with a hysterectomy and blood product transfusions.
Metastatic hepatic actinomycosis masquerading as distant metastases of ovarian cancer
Authors: Kim Young Sun , Lee Bo Yon , Jung Min Hyung
Published: February 2012

Actinomycosis is a chronic disease characterized by abscess, tissue fibrosis and draining sinuses. Pelvic actinomycosis in women most commonly occurs during ascending infections, which are usually associated with intrauterine devices; however, secondary hepatic actinomycosis, while rare, can also occur. We describe a patient with an unusual case of metastatic hepatic actinomycosis misdiagnosed as distant metastases of ovarian cancer.
Effects of preeclampsia on the yield of hematopoietic stem cells obtained from umbilical cord blood at delivery
Authors: Abdul Wahid Fadilah S. , Nasaruddin Mona Zaria , Mohd Idris Mohd Razif , Tusimin Maiza , Tumian Nor Rafeah , Abdullah Mahdy Zaleha
Published: February 2012

Aim:  To compare the numbers of cord blood CD34+ hematopoietic stem cells (HSC) between preeclampsia (PE) and control (non‐PE) subjects and to determine the factors that may influence this observation.

Methods:  Umbilical cord blood was collected from 28 PE and 19 non‐PE subjects. Nucleated and CD34+ cell counts were derived using the Trucount tube‐based stem cell enumeration kit on BD FACSCalibur.

Results:  The cord blood volume, nucleated and CD34+ cell counts were significantly reduced in PE subjects compared to non‐PE subjects. Among the PE subjects, systolic and diastolic blood pressure demonstrated a negative correlation with total nucleated and CD34+ cell counts. Gestational age at delivery influenced cord blood volume and nucleated cell counts, but not CD34+ cell counts. Birth weight and placental weight correlated strongly with cord blood volume, and nucleated and CD34+ cell counts. There were no correlations observed between cord blood parameters and maternal age, maternal white cell count, gravidity, route of delivery or neonatal gender among PE subjects.

Conclusion:  Preeclampsia has a negative impact on the yield of HSC obtained from cord blood at delivery. Maternal blood pressure, neonatal birth weight and placental weight are important factors influencing the numbers of cord blood HSC. These findings should be taken into consideration when selecting cord blood units from mothers with PE for banking. Selecting the heaviest term neonate might improve the yield of cord blood HSC obtained from PE mothers.
Isolated ‘sign of the horns’: A simple, pathognomonic, prenatal sonographic marker of Crisponi syndrome
Authors: Dessì Angelica , Fanos Vassilios , Crisponi Giangiorgio , Frau Alessandro , Ottonello Giovanni
Published: February 2012

The case of a patient presenting with Crisponi syndrome recently hospitalized at our institution is described. During pregnancy a diagnosis of this syndrome was hypothesized following sonographic observation of the fetus with the hands showing ‘the sign of the horns’. Such a finding, if isolated, as in our case, may represent a simple, pathognomonic sonographic marker of Crisponi syndrome.
Laparoscopic and open colorectal surgery: a prospective cost analysis
Authors: Dowson H. M. , Gage H. , Jackson D. , Qiao Y. , Williams P. , Rockall T. A.
Published: February 2012

Aim  Cost has been perceived to be a factor limiting the development of laparoscopic colorectal surgery. This study aimed to compare the costs of laparoscopic and open colorectal surgery.

Method  Patients undergoing laparoscopic or open elective colorectal surgery were recruited into a prospective study to evaluate the healthcare costs of each operative procedure in a district general hospital in England. All healthcare resources used (operation, hospital and community) were recorded and converted to costs in British pounds, 2006–2007. Costs of laparoscopic and open surgery were compared.

Results  In all, 201 consecutive patients consented and were recruited (131 laparoscopic, 70 open). Operative costs were greater in the laparoscopic group (£2049 vs£1263, P < 0.001) due to the costs of disposable instruments, but the hospital costs were less (£1807 vs£3468, P < 0.001) due to longer lengths of stay in the open group. Community costs were similar in the two groups and had little impact on the overall costs, which were not significantly different (£3875 laparoscopic vs£4383 open, P = 0.308). In the subgroup of patients with a stoma, overall costs in the laparoscopic group are higher (not significant).

Conclusion  The costs of laparoscopic and open colorectal surgery are broadly equivalent. If there is an associated improvement in patient benefit, then laparoscopic colorectal surgery may be considered to be cost effective compared with open surgery.
Low complication rate after stoma closure. Consultants attended 90% of the operations
Authors: Faunø L. , Rasmussen C. , Sloth K. K. , Sloth A. M. , Tøttrup A.
Published: February 2012

Aim  To evaluate complications after stoma closure.

Method  Using a retrospective review of 997 medical records, data were collected from all patients undergoing stoma closure at the Department of Surgery P, Aarhus University Hospital, Denmark, from 1996 to 2010. Patient data after Hartmann reversal and loop‐ileostomy closure were compared. Data regarding the grade of the operating surgeon and assistant were extracted.

Results  Out of 997 patients, 700 (70.6%) had a loop‐ileostomy closure and 172 (17.4%) had a Hartmann reversal. Postoperative mortality was 0.5%. Seven patients required re‐operation (0.7%). Morbidity was registered in 31.9% of the patients, with 131 (13.1%) having early complications and 187 (18.8%) having late complications. Wound infection was the most frequent early complication, which occurred in 31 patients (3.1%). Only 10 patients (1%) had an anastomotic leak. Incisional hernia was the most frequent late complication, occurring in 92 patients (9.3%). A consultant attended 90% of the operations. Junior surgeons never performed stoma closure without supervision. Body mass index was significantly associated with the development of incisional hernia. Hartmann reversal was associated with higher rates of complications compared with loop‐ileostomy closure. In patients with Hartmann reversal, stapled anastomosis was associated with stricture in 12 out of 95 cases (12.6%), whereas hand‐sewn anastomosis was not associated with stricture (0 out of 64 patients; 0%; P < 0.05).

Conclusion  Stoma closure is associated with low rates of leakage. A favourable case mix and high degree of consultant attendance may explain the good results.
Synchronous resection of colorectal cancer and liver metastases: comparative views of colorectal and liver surgeons
Authors: Qureshi M. S. , Goldsmith P. J. , Maslekar S. , Prasad K. R. , Botterill I. D.
Published: February 2012

Aim  The optimal management of patients presenting with colorectal cancer and synchronous liver metastases is controversial. This survey was intended to summarize the opinions of UK colorectal and liver surgeons on the specific issues pertaining to synchronous resection.

Method  A validated electronic survey was sent to the consultant members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the Association of Upper Gastrointestinal Surgeons (AUGIS). The questions were structured to allow direct comparison between the two groups of the responses obtained.

Results  Four hundred and twenty‐four specialist colorectal surgeons and 52 specialist hepatobiliary surgeons were identified from the register of their respective associations. Responses were obtained from 133 (31%) colorectal and 22 (42%) liver surgeons. A majority of both groups of surgeons felt that synchronous resection was a valid therapeutic option. A majority of both groups believed that synchronous resection was justified despite the options of laparoscopic surgery and enhanced recovery programmes for each discipline. Agreed possible advantages of synchronous resections were: a decrease in the overall length of hospital stay, cost and patient anxiety. The major concern about synchronous resections was an excessive overall physiological insult. Specific scenarios indicated that synchronous resection was favoured for major/complex major colorectal resection with minor liver resection or most colorectal resections not involving an anastomosis with either a minor or major liver resection.

Conclusion  Although significant concerns relating to synchronous resection remain amongst colorectal and liver surgeons, a majority of them felt that synchronous resections could be offered to appropriately selected patients.
Risk factors for chronic pouchitis after ileal pouch–anal anastomosis: a prospective cohort study
Authors: Hashavia E. , Dotan I. , Rabau M. , Klausner J. M. , Halpern Z. , Tulchinsky H.
Published: February 2012

Aim  The association between various demographic, clinical and pathological parameters and the evolution of chronic pouchitis was evaluated.

Method  All ulcerative colitis patients who underwent ileal pouch anal anastomosis (1981–2009) were followed prospectively in a comprehensive pouch clinic. We examined risk factors including the presence of appendiceal inflammation and backwash ileitis in the colonic specimen, gender, ethnicity, age at disease onset, disease duration, extent of colitis, presence of extraintestinal manifestations (e.g. primary sclerosing cholangitis), family history of inflammatory bowel disease, indication for surgery, medical treatment, age at operation, staged procedure, diverting ileostomy and length of follow‐up. Univariate analysis was performed on all risk factors followed by logistic regression analysis.

Results  The 201 enrolled patients (106 women, age at surgery 35 ± 15 years) were followed for a mean of 108 months. One hundred and thirty‐eight (69%) had either a normal pouch or episodes of acute pouchitis and 63 (31%) developed chronic pouchitis. On univariate analysis the presence of an ileostomy (P = 0.017), pancolitis (P = 0.008), shorter disease duration (P = 0.04) and longer follow‐up (P = 0.01) were identified as risk factors for chronic pouchitis. Multivariate analysis showed that patients with pancolitis (OR 3.26, 95% CI 1.20–8.85) and longer follow‐up (OR 1.09, 95% CI 1.01–1.18) were more likely to develop chronic pouchitis. There was also an association to disease duration but this did not reach a level of significance.

Conclusions  Pancolitis and longer follow‐up are directly related to the development of chronic pouchitis.
Effects of intravitreal injection of KH902, a vascular endothelial growth factor receptor decoy, on the retinas of streptozotocin‐induced diabetic rats
Authors: Huang J. , Li X. , Li M. , Li S. , Xiao W. , Chen X. , Cai M. , Wu Q. , Luo D. , Tang S. , Luo Y.
Published: February 2012

Aims: KH902 is a fusion protein that can bind vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) through its binding ligand taken from the domains of VEGF receptor 1 and VEGF receptor 2 (VEGFR2). This study was to investigate the effects of intravitreal injection of KH902 on the retinas of streptozotocin‐induced diabetic rats.

Methods: Two weeks after induction of diabetes, the left eyes of diabetic rats in each group received an intravitreal injection of phosphate‐buffered saline (PBS), Avastin or KH902 solution, respectively. Four weeks after intravitreal injection, retinal electrophysiological function and the integrity of inner blood retinal barrier (iBRB) were measured by electroretinogram and Evans blue perfusion. The protein levels of VEGF signal pathway were assayed by western blot. The expression and distribution of claudin‐5 and occludin were analysed by double immunofluorescent staining under confocal microscope. The expression of VEGFR2 and PlGF was measured by immunohistochemistry.

Results: Four weeks after intravitreal injection, KH902‐treated rats had better retinal electrophysiological function, less retinal vessel leakage and lower levels of VEGFR2, PI3K, AKT, p‐AKT, p‐ERK and p‐SRC than PBS or Avastin‐treated rats. The distribution of claudin‐5 and occludin in the retinal vessels of diabetic rats treated by KH902 was smoother and more uniform than those of diabetic rats treated by PBS or Avastin. The expression of PlGF and VEGFR2 in KH902‐treated rats was decreased compared with those in PBS or Avastin‐treated rats.

Conclusions: KH902 could improve retinal electrophysiological function and inhibit the breakdown of iBRB by inhibiting the expression of VEGFR2, PlGF and PI3K, and the activation of SRC, AKT and ERK.
The effect of linagliptin on glycaemic control and tolerability in patients with type 2 diabetes mellitus: a systematic review and meta‐analysis
Authors: Singh‐Franco D. , McLaughlin‐Middlekauff J. , Elrod S. , Harrington C.
Published: February 2012

Aim: Linagliptin is a new dipeptidyl peptidase‐4 inhibitor recently approved for use in the USA. The objective of this systematic review and meta‐analysis was to assess effect of linagliptin on glycaemic control, biomarkers and incidence of adverse events (AEs) in patients with type 2 diabetes mellitus.

Methods: Five published and four unpublished randomized, clinical trials were identified from multiple databases. Qualitative assessments and quantitative analyses were performed.

Results: Nine studies included 4246 participants with 53% men, 59.4% Caucasians, 38.7% Asians, and age range 45–69 years. Linagliptin was given as monotherapy (vs. placebo) or combined with metformin (vs. metformin + placebo), sulphonylurea (vs. sulphonylurea + placebo) or pioglitazone (vs. pioglitazone + placebo). Linagliptin 5 mg/day for 12–24 weeks, significantly reduced haemoglobin A1c (HbA1c) (−0.63%, p < 0.00001), fasting plasma glucose (FPG) (−1.01 mmol/l, p < 0.00001) and improved disposition index (DI, product of insulin sensitivity and acute insulin secretion) (p = 0.0001). Linagliptin monotherapy was not more effective than metformin at reducing HbA1c or FPG. Similar proportion of patients in linagliptin and placebo groups reported AEs including upper respiratory tract infections, headaches, nausea, hypertension and back pain.

Conclusions: Linagliptin was associated with modest but significant reduction in HbA1c and FPG and improved DI after 12–24 weeks. Patients who would probably benefit most are those with HbA1c <9%, already on an active agent, compliant with weight reduction strategies, and can recognize and manage hypoglycaemia, fluid retention and upper respiratory tract infections. Long‐term studies are needed to determine durability of response, incidence of microvascular and macrovacular complications, cost‐effectiveness and safety.
Effects of JNJ‐38431055, a novel GPR119 receptor agonist, in randomized, double‐blind, placebo‐controlled studies in subjects with type 2 diabetes
Authors: Katz L. B. , Gambale J. J. , Rothenberg P. L. , Vanapalli S. R. , Vaccaro N. , Xi L. , Sarich T. C. , Stein P. P.
Published: February 2012

Aim: G‐protein coupled receptor agonists are currently under investigation for their potential utility in patients with type 2 diabetes mellitus (T2DM). The objective was to determine the pharmacokinetics, pharmacodynamics, safety and tolerability of GPR119 agonist, JNJ‐38431055 in T2DM subjects.

Methods: This was a randomized, double‐blind, placebo‐ and positive‐controled, single‐dose cross‐over study and a randomized, double‐blind, placebo‐controled multiple‐dose parallel design study. The study was conducted at 4 US research centres. Two different experiments involving 25 and 32 different subjects were performed in male and female subjects, aged 25–60 years, mean body mass index between 22 and 39.9 kg/m2 who had T2DM diagnosed 6 months to 10 years before screening. JNJ‐38431055 (100 and 500 mg) or sitagliptin (100 mg) as a single‐dose or JNJ‐38431055 (500 mg) once daily for 14 consecutive days were tested. Effects on stimulated plasma glucose, insulin, C‐peptide and incretin concentrations were pre‐specified outcomes.

Results: JNJ‐38431055 was well tolerated and not associated with hypoglycaemia. Plasma systemic exposure of JNJ‐38431055 increased as the dose increased, was approximately two‐fold greater after multiple‐dose administration, and attained steady‐state after approximately 8 days. Compared with placebo, single‐dose administration of oral JNJ‐38431055 decreased glucose excursion during an oral glucose tolerance test, but multiple‐dose administration did not alter 24‐h weighted mean glucose. Multiple dosing of JNJ‐38431055 increased post‐meal total glucagon‐like peptide 1 and gastric insulinotropic peptide concentrations compared to baseline.

Conclusions: These studies provide evidence of limited glucose lowering and incretin activity for JNJ‐38431055 in subjects with T2DM.
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in Cavalier King Charles spaniel dogs–part II: candidate gene study
Authors: Hartley Claudia , Barnett Keith C. , Pettitt Louise , Forman Oliver P. , Blott Sarah , Mellersh Cathryn S.
Published: February 2012

Purpose  To identify causative mutation(s) for congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in Cavalier King Charles spaniel (CKCS) dogs using a candidate gene approach.

Methods  DNA samples from 21 cases/parents were collected. Canine candidate genes (CCGs) for similar inherited human diseases were chosen. Twenty‐eight candidate genes were identified by searching the Pubmed OMIM database (http://www.ncbi.nlm.nih.gov/omim). Canine orthologues of human candidate genes were identified using the Ensembl orthologue prediction facility (http://www.ensembl.org/index.html). Two microsatellites flanking each candidate gene were selected, and primers to amplify each microsatellite were designed using the Whitehead Institute primer design website (http://frodo.wi.mit.edu/primer3/). The microsatellites associated with all 28 CCGs were genotyped on a panel of 21 DNA samples from CKCS dogs (13 affected and eight carriers). Genotyping data was analyzed to identify markers homozygous in affected dogs and heterozygous in carriers (homozygosity mapping).

Results  None of the microsatellites associated with 25 of the CCGs displayed an association with CKCSID in the 21 DNA samples tested. Three CCGs associated microsatellites were monomorphic across all samples tested.

Conclusions  Twenty‐five CCGs were excluded as cause of CKCSID. Three CCGs could not be excluded from involvement in the inheritance of CKCSID.

Support  Kennel Club Charitable Trust grant.
Reciprocal Expertise Affirmation and Shared Expertise Perceptions in Work Teams: Their Implications for Coordinated Action and Team Performance
Authors: Grutterink Hanneke , Van der Vegt Gerben S. , Molleman Eric , Jehn Karen A.
Published: February 2012

In this paper we argue that reciprocal expertise affirmation—i.e. the mutual recognition by team members that they respect, value, and affirm each other's expertise—is positively related to team performance, but only in teams with high levels of shared expertise perceptions. Moreover, we propose that the joint effects of teams’ reciprocal expertise affirmation and sharedness of expertise perceptions on team performance will be mediated by coordinated action. Data from 226 members of 39 student teams, working on a realistic four‐week business simulation, supported our hypotheses. Our findings highlight the importance of reciprocal expertise affirmation for the effective functioning of work teams.
National Identity and Perceived Discrimination Predict Changes in Ethnic Identity Commitment: Evidence from a Longitudinal Study of Latino College Students
Authors: Fuller‐Rowell Thomas E. , Ong Anthony D. , Phinney Jean S.
Published: February 2012

The current study tests the hypothesis that the influence of perceived discrimination on ethnic identity commitment is moderated by national identity (a person's psychological affiliation to their country of residence). A positive direct effect of national identity on ethnic identity commitment was also predicted. Analyses are based on a sample of Latino college students in the United States followed across eight consecutive semesters (N= 97; Mage= 18). In support of the hypotheses, a significant interaction was found between discrimination and national identity. In particular, perceived discrimination in the first year of college was positively associated with changes in ethnic identity commitment across the college years among participants with a weaker national identity, but negatively associated with changes in ethnic identity commitment among participants with a stronger national identity. Higher levels of national identity were also associated with greater increases in ethnic identity commitment over time.