bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo transcriptome sequencing of axolotl blastema for identification of differentially expressed genes during limb regeneration
Authors: Wu Cheng-Han , Tsai Mong-Hsun , Ho Chia-Chuan , Chen Chien-Yu , Lee Hsuan-Shu
Published: July 2013

Background

Salamanders are unique among vertebrates in their ability to completely regenerate amputated limbs through the mediation of blastema cells located at the stump ends. This regeneration is nerve-dependent because blastema formation and regeneration does not occur after limb denervation. To obtain the genomic information of blastema tissues, de novo transcriptomes from both blastema tissues and denervated stump ends of Ambystoma mexicanum (axolotls) 14 days post-amputation were sequenced and compared using Solexa DNA sequencing.

Results

The sequencing done for this study produced 40,688,892 reads that were assembled into 307,345 transcribed sequences. The N50 of transcribed sequence length was 562 bases. A similarity search with known proteins identified 39,200 different genes to be expressed during limb regeneration with a cut-off E-value exceeding 10-5. We annotated assembled sequences by using gene descriptions, gene ontology, and clusters of orthologous group terms. Targeted searches using these annotations showed that the majority of the genes were in the categories of essential metabolic pathways, transcription factors and conserved signaling pathways, and novel candidate genes for regenerative processes. We discovered and confirmed numerous sequences of the candidate genes by using quantitative polymerase chain reaction and in situ hybridization.

Conclusion

The results of this study demonstrate that de novo transcriptome sequencing allows gene expression analysis in a species lacking genome information and provides the most comprehensive mRNA sequence resources for axolotls. The characterization of the axolotl transcriptome can help elucidate the molecular mechanisms underlying blastema formation during limb regeneration.
Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer
Authors: Bravo Dawn T , Yang Yi-Lin , Kuchenbecker Kristopher , Hung Ming-Szu , Xu Zhidong , Jablons David M , You Liang
Published: July 2013

Background

Wnt-2 plays an oncogenic role in cancer, but which Frizzled receptor(s) mediates the Wnt-2 signaling pathway in lung cancer remains unclear. We sought to (1) identify and evaluate the activation of Wnt-2 signaling through Frizzled-8 in non-small cell lung cancer, and (2) test whether a novel expression construct dominant negative Wnt-2 (dnhWnt-2) reduces tumor growth in a colony formation assay and in a xenograft mouse model.

Methods

Semi-quantitative RT-PCR was used to identify the expression of Wnt-2 and Frizzled-8 in 50 lung cancer tissues from patients. The TCF reporter assay (TOP/FOP) was used to detect the activation of the Wnt canonical pathway in vitro. A novel dnhWnt-2 construct was designed and used to inhibit activation of Wnt-2 signaling through Frizzled-8 in 293T, 293, A549 and A427 cells and in a xenograft mouse model. Statistical comparisons were made using Student’s t-test.

Results

Among the 50 lung cancer samples, we identified a 91% correlation between the transcriptional increase of Wnt-2 and Frizzled-8 (p<0.05). The Wnt canonical pathway was activated when both Wnt-2 and Frizzled-8 were co-expressed in 293T, 293, A549 and A427 cells. The dnhWnt-2 construct we used inhibited the activation of Wnt-2 signaling in 293T, 293, A549 and A427 cells, and reduced the colony formation of NSCLC cells when β-catenin was present (p<0.05). Inhibition of Wnt-2 activation by the dnhWnt-2 construct further reduced the size and mass of tumors in the xenograft mouse model (p<0.05). The inhibition also decreased the expression of target genes of Wnt signaling in these tumors.

Conclusions

We demonstrated an activation of Wnt-2 signaling via the Frizzled-8 receptor in NSCLC cells. A novel dnhWnt-2 construct significantly inhibits Wnt-2 signaling, reduces colony formation of NSCLC cells in vitro and tumor growth in a xenograft mouse model. The dnhWnt-2 construct may provide a new therapeutic avenue for targeting the Wnt pathway in lung cancer.
Chemokine (C-X-C) ligand 1 (CXCL1) protein expression is increased in aggressive bladder cancers
Authors: Miyake Makito , Lawton Adrienne , Goodison Steve , Urquidi Virginia , Gomes-Giacoia Evan , Zhang Ge , Ross Shanti , Kim Jeongsoon , Rosser Charles J
Published: July 2013

Background

Chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), may regulate tumor epithelial-stromal interactions that facilitate tumor growth and invasion. Studies have linked CXCL1 expression to gastric, colon and skin cancers, but limited studies to date have described CXCL1 protein expression in human bladder cancer (BCa).

Methods

CXCL1 protein expression was examined in 152 bladder tissue specimens (142 BCa) by immunohistochemical staining. The expression of CXCL1 was scored by assigning a combined score based on the proportion of cells staining and intensity of staining. CXCL1 expression patterns were correlated with clinicopathological features and follow-up data.

Results

CXCL1 protein expression was present in cancerous tissues, but was entirely absent in benign tissue. CXCL1 combined immunostaining score was significantly higher in high-grade tumors relative to low-grade tumors (p = 0.012). Similarly, CXCL1 combined immunostaining score was higher in high stage tumors (T2-T4) than in low stage tumors (Ta-T1) (p < 0.0001). An increase in the combined immunostaining score of CXCL1 was also associated with reduced disease-specific survival.

Conclusion

To date, this is the largest study describing increased CXCL1 protein expression in more aggressive phenotypes in human BCa. Further studies are warranted to define the role CXCL1 plays in bladder carcinogenesis and progression.
Effects of geodemographic profiles on healthcare service utilization: a case study on cardiac care in Ontario, Canada
Authors: Tao Li , Liu Jiming , Xiao Bo
Published: July 2013

Background

Although literature has associated geodemographic factors with healthcare service utilization, little is known about how these factors — such as population size, age profile, service accessibility, and educational profile — interact to influence service utilization. This study fills this gap in the literature by examining both the direct and the moderating effects of geodemographic profiles on the utilization of cardiac surgery services.

Methods

We aggregated secondary data obtained from Statistics Canada and Cardiac Care Network of Ontario to derive the geodemographic profiles of Ontario and the corresponding cardiac surgery service utilization in the years between 2004 and 2007. We conducted a two-step test using Partial Least Squares-based structural equation modeling to investigate the relationships between geodemographic profiles and healthcare service utilization.

Results

Population sizeandage profilehave direct positive effects onservice utilization(β = 0.737,p < 0.01;β = 0.284,p < 0.01, respectively), whereasservice accessibilityis negatively associated withservice utilization(β = -0.210,p < 0.01).Service accessibilitydecreases the effect ofpopulation sizeonservice utilization(β = -0.606,p < 0.01), andeducational profileweakens the effects ofpopulation sizeandage profileonservice utilization(β = -0.595,p < 0.01;β = -0.286,p < 0.01, respectively).

Conclusions

In this study, we found that (1)service accessibilityhas a moderating effect on the relationship betweenpopulation sizeandservice utilization, and (2)educational profilehas moderating effects on both the relationship betweenpopulation sizeandservice utilization, and the relationship betweenage profileandservice utilization. Our findings suggest that reducing regional disparities in healthcare service utilization should take into account the interaction of geodemographic factors such as service accessibility and education. In addition, the allocation of resources for a particular healthcare service in one area should consider the geographic distribution of the same services in neighboring areas, as patients may be willing to utilize these services in areas not far from where they reside.
Validity and responsiveness of EuroQol-5 dimension (EQ-5D) versus Short Form-6 dimension (SF-6D) questionnaire in chronic pain
Authors: Obradovic Marko , Lal Arun , Liedgens Hiltrud
Published: July 2013

Background

Assessments of health-related quality of life and particularly utility values are important components of health economic analyses. Several instruments have been developed to measure utilities. However no consensus has emerged regarding the most appropriate instrument within a therapeutic area such as chronic pain. The study compared two instruments – EQ-5D and SF-6D – for their performance and validity in patients with chronic pain.

Methods

Pooled data from three randomised, controlled clinical trials with two active treatment groups were used. The included patients suffered from osteoarthritis knee pain or low back pain. Differences between the utility measures were compared in terms of mean values at baseline and endpoint, Bland–Altman analysis, correlation between the dimensions, construct validity, and responsiveness.

Results

The analysis included 1977 patients, most with severe pain on the Numeric Rating Scale. The EQ-5D showed a greater mean change from baseline to endpoint compared with the SF-6D (0.43 to 0.58 versus 0.59 to 0.64). Bland–Altman analysis suggested the difference between two measures depended on the health status of a patient. Spearmans rank correlation showed moderate correlation between EQ-5D and SF-6D dimensions. Construct validity showed both instruments could differentiate between patient subgroups with different severities of adverse events and analgesic efficacies but larger differences were detected with the EQ-5D. Similarly, when anchoring the measures to a disease-specific questionnaire – Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) – both questionnaires could differentiate between WOMAC severity levels but the EQ-5D showed greater differences. Responsiveness was also higher with the EQ-5D and for the subgroups in which improvements in health status were expected or when WOMAC severity level was reduced the improvements with EQ-5D were higher than with SF-6D.

Conclusions

This analysis showed that the mean EQ-5D scores were lower than mean SF-6D scores in patients with chronic pain. EQ-5D seemed to have higher construct validity and responsiveness in these patients.
Comparative full length genome sequence analysis of usutu virus isolates from Africa
Authors: Nikolay Birgit , Dupressoir Anne , Firth Cadhla , Faye Ousmane , Boye Cheikh S , Diallo Mawlouth , Sall Amadou A
Published: July 2013

Background

Usutu virus (USUV), a flavivirus belonging to the Japanese encephalitis serocomplex, was identified in South Africa in 1959 and reported for the first time in Europe in 2001. To date, full length genome sequences have been available only for the reference strain from South Africa and a single isolate from each of Austria, Hungary, and Italy.

Methods

We sequenced four USUV isolates from Senegal and the Central African Republic (CAR) between 1974 and 2007 and compared the sequence data to USUV strains from Austria, Hungary, Italy, and South Africa using a Bayesian Markov chain Monte Carlo method. We further clarified the taxonomic status of a USUV strain isolated in CAR in 1969 and proposed earlier as a subtype of USUV due to an asymetric serological cross-reactivity with USUV reference strain.

Results

A comparison of the four newly obtained USUV sequences with those from SouthAfrica_1959, Vienna_2001, Budapest_2005, and Italy_2009 revealed that they are all 96-99% and 99% similar at the nucleotide and amino acid levels, respectively. The phylogenetic relationships between these sequences indicated that a strain isolated in Senegal in 1993 is most closely related to the USUV strains detected in Europe. Analysis of a strain isolated from a human in CAR in 1981 (CAR_1981) revealed the presence of specific amino acid substitutions and a deletion in the 3′ noncoding region. This is the first fully sequenced human USUV isolate.

The putative USUV subtype, CAR_1969, was 81% and 94% identical at the nucleotide and amino acid levels, respectively, compared to the other USUV strains. Our phylogenetic analyses support the serological identification of CAR_1969 as a subtype of USUV.

Conclusions

In this study, we investigate the genetic diversity of USUV in Africa and the phylogenetic relationship of isolates from Africa and Europe for the first time. The results suggest a low genetic diversity within USUV, the existence of a distinct USUV subtype strain, and support the hypothesis that USUV was introduced to Europe from Africa. Further sequencing and analysis of USUV isolates from other African countries would contribute to a better understanding of its genetic diversity and geographic distribution.
Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice
Authors: Brandenberger Christina , Rowley Nicole L , Jackson-Humbles Daven N , Zhang Quanxuan , Bramble Lori A , Lewandowski Ryan P , Wagner James G , Chen Weimin , Kaplan Barbara L , Kaminski Norbert E , Baker Gregory L , Worden Robert M , Harkema Jack R
Published: July 2013

Background

With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease.

Methods

We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 μg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses.

Results

Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses.

Conclusions

These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon secondary allergen exposures. Whereas SNP caused innate immune responses at high doses in non-allergic mice, the adjuvant effects of SNP were found at lower doses in allergic mice and were Th2/Th17 related. In conclusion, these findings in mice suggest that individuals exposed to SNP might be more prone to manifest allergic airway disease, due to adjuvant-like properties of SNP.
Quality of life and long-term outcomes of octo- and nonagenarians following acute care surgery: a cross sectional study
Authors: Gazala Sayf , Tul Yvonne , Wagg Adrian , Widder Sandy L , Khadaroo Rachel G
Published: July 2013

Background

While advanced age is often associated with poorer surgical outcomes, long-term age-related health status following acute care surgery is unknown. The objective of our study was to assess post-operative cognitive impairment, functional status, and quality of life in elderly patients who underwent emergency surgery.

Methods

We identified 159 octo- and nonagenarians who underwent emergency surgery between 2008 and 2010 at a single tertiary hospital. Patients were grouped into three cohorts: 1, 2, and 3 years post-operative. We conducted a survey in 2011, with octo- and nonagenarians regarding the impact of emergency surgical procedures. Consenting participants responded to four survey questionnaires: (1) Abbreviated Mental Test Score-4, (2) Barthel Index, (3) Vulnerable Elders Survey, and (4) EuroQol-5 Dimensional Scale.

Results

Of the 159 octo- and nonagenarians, 88 (55.3%) patients were alive at the time of survey conduction, and 55 (62.5%) of the surviving patients consented to participate. At 1, 2, and 3 years post-surgery, mortality rates were 38.5%, 44.7%, and 50.0%, respectively. More patients had cognitive impairments at 3 years (33.3%) than at 1 (9.5%) and 2 years (9.1%) post-operatively. No statistical difference in the ability to carry out activities of daily living or functional decline with increasing time post-operatively. However, patients perceived a significant health decline with the greater time that passed following surgery.

Conclusions

Our study showed that half of the patients over the age of 80 are surviving up to 3 years post-operatively. While post-operative functional status appears to be stable across the 3 cohorts of patients, perceived health status declines over time. Understanding the long-term post-operative impact on cognitive impairment, functional status, and quality of life in elderly patients who undergo acute care surgery allows health care professionals to predict their patients’ likely post-operative needs.
Risk factors for the development of reexpansion pulmonary edema in patients with spontaneous pneumothorax
Authors: Yoon Jeong-Seob , Suh Jong-Hui , Choi Si Young , Kwon Jong Bum , Lee Bae Young , Lee Sang Haak , Kim Chi Kyung , Park Chan Beom
Published: July 2013

Background

Reexpansion pulmonary edema (REPE) is known as a rare and fatal complication after tube thoracostomy.

Objectives

We investigated the risk factors for the development of REPE in patients with spontaneous pneumothorax.

Methods

We selected patients who were diagnosed with spontaneous pneumothorax and were initially treated with tube thoracostomy between August 1, 2003 and December 31, 2011. The patients’ electronic medical records, including operative notes and chest x-ray and computed tomography scans, were reviewed.

Results

REPE developed in 49 of the 306 patients (16.0%). REPE was more common in patients with diabetes (14.3% vs 3.9%, P = 0.004) or tension pneumothorax (46.8% vs 16.2%, P = 0.000). The pneumothorax was larger in patients with REPE than without REPE (57.0 ± 16.0% vs 34.2 ± 17.6%, P = 0.000), and the incidence of REPE increased with the size of pneumothorax. On multivariate analysis, diabetes mellitus [(odds ratio (OR) = 9.93, P = 0.003), and the size of pneumothorax (OR = 1.07, P = 0.000) were independent risk factors of REPE.

Conclusions

The presence of diabetes increases the risk of REPE development in patients with spontaneous pneumothorax. The risk of REPE also increases significantly with the size of pneumothorax.
Does high biodiversity reduce the risk of Lyme disease invasion?
Authors: Bouchard Catherine , Beauchamp Guy , Leighton Patrick A , Lindsay Robbin , Bélanger Denise , Ogden Nick H
Published: July 2013

Background

It has been suggested that increasing biodiversity, specifically host diversity, reduces pathogen and parasite transmission amongst wildlife (causing a “dilution effect”), whereby transmission amongst efficient reservoir hosts, (e.g. Peromyscus spp. mice for the agent of Lyme disease Borrelia burgdorferi) is reduced by the presence of other less efficient host species. If so, then increasing biodiversity should inhibit pathogen and parasite invasion.

Methods

We investigated this hypothesis by studying invasion of B. burgdorferi and its tick vector Ixodes scapularis in 71 field sites in southeastern Canada. Indices of trapped rodent host diversity, and of biodiversity of the wider community, were investigated as variables explaining the numbers of I. scapularis collected and B. burgdorferi infection in these ticks. A wide range of alternative environmental explanatory variables were also considered.

Results

The observation of low I. scapularis abundance and low B. burgdorferi infection prevalence in sites where I. scapularis were detected was consistent with early-stage invasion of the vector. There were significant associations between the abundance of ticks and season, year of study and ambient temperature. Abundance of host-seeking larvae was significantly associated with deer density, and abundance of host-seeking larvae and nymphs were positively associated with litter layer depth. Larval host infestations were lower where the relative proportion of non-Peromyscus spp. was high. Infestations of hosts with nymphs were lower when host species richness was higher, but overall nymphal abundance increased with species richness because Peromyscus spp. mouse abundance and host species richness were positively correlated. Nymphal infestations of hosts were lower where tree species richness was higher. B. burgdorferi infection prevalence in ticks varied significantly with an index of rates of migratory bird-borne vector and pathogen invasion.

Conclusions

I. scapularis abundance and B. burgdorferi prevalence varied with explanatory variables in patterns consistent with the known biology of these species in general, and in the study region in particular. The evidence for a negative effect of host biodiversity on I. scapularis invasion was mixed. However, some evidence suggests that community biodiversity beyond just host diversity may have direct or indirect inhibitory effects on parasite invasion that warrant further study.
A prospective phase II study of L-asparaginase- CHOP plus radiation in newly diagnosed extranodal NK/T-cell lymphoma, nasal type
Authors: Lin Ningjing , Song Yuqin , Zheng Wen , Tu Meifeng , Xie Yan , Wang Xiaopei , Ping Lingyan , Ying Zhitao , Zhang Chen , Deng Lijuan , Liu Weiping , Zhu Jun
Published: July 2013

Purpose

To explore the efficacy and safety of L-asparaginase in newly-diagnosed extranodal nature killer (NK)/T –cell lymphoma (ENKTL), we conducted a prospective phase II study of L-asparaginase, cyclophosphamide, vincristine, doxorubicin and dexamethasone (CHOP-L) regimen in combination with radiotherapy.

Patients and methods

Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. Treatment included 6–8 cycles of CHOP-L (cyclophosphamide, 750 mg/m2 day 1; vincristine, 1.4 mg/m2 day 1 (maximal dose 2 mg), doxorubicin 50 mg/m2 day 1; dexamethasone 10 mg days 1–8; L-asparaginase 6000 u/m2 days 2–8). Radiotherapy was scheduled after 4–6 cycles of CHOP-L regimen, depending on stage and primary anatomic site. The primary endpoint was complete response (CR) rate.

Results

A total of 38 eligible patients were enrolled. The median age was 40.5 years (range, 15 to 71 years). Their clinical characteristics were male to female ratio, 24:14; Ann Arbor stage I, 20; II, 11; III, 3; IV, 4. CR and overall response rates were 81.6% (95% CI, 69.3% to 93.9%) and 84.2%, respectively. With a median follow-up of 25 months, the 2-year overall survival, progression-free survival and disease-free survival rates were 80.1% (95%CI, 73.3% to 86.9%), 81% (95%CI, 74.5% to 87.5%) and 93.6% (95%CI, 89.3% to 97.9%), respectively. The major adverse events were myelosuppression, liver dysfunction, and digestive tract toxicities. Grade 3 to 4 leukopenia and neutropenia were 76.3% and 84.2%, respectively. No treatment-related death was observed.

Conclusion

CHOP-L chemotherapy in combination with radiotherapy is a safe and highly effective treatment for newly diagnosed ENKTL.
Health‐related quality of life, assessed with a disease‐specific questionnaire, in Swedish adults suffering from well‐diagnosed food allergy to staple foods
Authors: Jansson Sven‐Arne , Heibert‐Arnlind Marianne , Middelveld Roelinde JM , Bengtsson Ulf J , Sundqvist Ann‐Charlotte , Kallström‐Bengtsson Ingrid , Marklund Birgitta , Rentzos Georgios , Åkerström Johanna , Östblom Eva , Dahlén Sven‐Erik , Ahlstedt Staffan
Published: July 2013

Background

Our aim was to investigate the factors that affect health related quality of life (HRQL) in adult Swedish food allergic patients objectively diagnosed with allergy to at least one of the staple foods cow's milk, hen's egg or wheat. The number of foods involved, the type and severity of symptoms, as well as concomitant allergic disorders were assessed.

Methods

The disease‐specific food allergy quality of life questionnaire (FAQLQ‐AF), developed within EuroPrevall, was utilized. The questionnaire had four domains: Allergen Avoidance and Dietary Restrictions (AADR), Emotional Impact (EI), Risk of Accidental Exposure (RAE) and Food Allergy related Health (FAH). Comparisons were made with the outcome of the generic questionnaire EuroQol Health Questionnaire, 5 Dimensions (EQ‐5D). The patients were recruited at an outpatient allergy clinic, based on a convincing history of food allergy supplemented by analysis of specific IgE to the foods in question. Seventy‐nine patients participated (28 males, 51 females, mean‐age 41 years).

Results

The domain with the most negative impact on HRQL was AADR, assessing the patients’ experience of dietary restrictions. The domain with the least negative impact on HRQL was FAH, relating to health concerns due to the food allergy. One third of the patients had four concomitant allergic disorders, which had a negative impact on HRQL. Furthermore, asthma in combination with food allergy had a strong impact. Anaphylaxis, and particularly prescription of an epinephrine auto‐injector, was associated with low HRQL. These effects were not seen using EQ‐5D. Analyses of the symptoms revealed that oral allergy syndrome and cardiovascular symptoms had the greatest impact on HRQL. In contrast, no significant effect on HRQL was seen by the number of food allergies.

Conclusions

The FAQLQ‐AF is a valid instrument, and more accurate among patients with allergy to staple foods in comparison to the commonly used generic EQ‐5D. It adds important information on HRQL in food allergic adults. We found that the restrictions imposed on the patients due to the diet had the largest negative impact on HRQL. Both severity of the food allergy and the presence of concomitant allergic disorders had a profound impact on HRQL.
Study protocol: a systematic review of pediatric shared decision making
Authors: Wyatt Kirk D , Prutsky Lopez Gabriela , Domecq Garces Juan Pablo , Erwin Patricia , Brinkman William B , Montori Victor M , LeBlanc Annie
Published: July 2013

Background

Shared decision making in pediatrics is unique because it often involves active participation of both the child or adolescent patient and his or her caregiver(s) in the decision making process with the clinician or care team, and the extent to which the patient is involved is commensurate with their developmental level. However, little is known about the nature of pediatric-specific shared decision making interventions and their impact.

Methods/Design

We will perform a systematic review with the objective of summarizing the nature of shared decision making practices, tools, techniques and technologies in the pediatric setting as well as their effects. A literature search will include Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Library, Web of Science, Scopus and Ovid PsycInfo databases in addition to consultation of a group of shared decision making experts to identify unpublished or in-progress works. We will include original research studies involving patients <18 years, their caregivers, or both, and summarize methods and approaches designed to engage participants in the health care decision making process with clinicians. Perinatal and research participation decisions will be excluded. Descriptions of participants involved, interventions used and the measured outcomes will be reported. Quality assessment will be performed according to the design of each study, where possible.

Discussion

We anticipate that the paucity of published quantitative data and the heterogeneous nature of the reported results will preclude quantitative analysis. In this event, a meta-narrative approach will be undertaken.

Systematic review registration

PROSPERO registration number:CRD42013004761
Extended pancreas donor program – the EXPAND study rationale and study protocol
Authors: Proneth Andrea , Schnitzbauer Andreas A , Zeman Florian , Foerster Johanna R , Holub Ines , Arbogast Helmut , Bechstein Wolf O , Becker Thomas , Dietz Carsten , Guba Markus , Heise Michael , Jonas Sven , Kersting Stephan , Klempnauer Jürgen , Manekeller Steffen , Müller Volker , Nadalin Silvio , Nashan Björn , Pascher Andreas , Rauchfuss Falk , Ströhlein Michael A , Schemmer Peter , Schenker Peter , Thorban Stefan , Vogel Thomas , Rahmel Axel O , Viebahn Richard , Banas Bernhard , Geissler Edward K , Schlitt Hans J , Farkas Stefan A
Published: July 2013

Background

Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients.

Methods/Design

This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation.

Discussion

The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.

Trial registration

Trial registered at:
NCT01384006
Outbreak of multidrug-resistant Klebsiella pneumoniae carrying qnrB1 and bla
CTX-M15
in a French intensive care unit
Authors: Filippa Nathalie , Carricajo Anne , Grattard Florence , Fascia Pascal , El Sayed Faten , Defilippis Jean Pierre , Berthelot Philippe , Aubert Gerald
Published: July 2013

Background

The prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is increasing globally and is a major clinical concern. Between June 2008 and September 2009, 4% of patients in an intensive care unit (ICU) were found to be colonized or infected by strains of Klebsiella pneumoniae multiresistant to ceftazidime, ciprofloxacin, and tobramycin; an investigation was initiated and isolates were characterized by molecular typing and resistance patterns.

Methods

Antibiotic susceptibilities were determined by Vitek2®, Etest®, and agar dilution. Gene encoding beta-lactamases and plasmid-mediated quinolone resistance PMQR determinants (qnr, aac(6′)-Ib) were characterized by PCR, sequencing, and transfer assays. DiversiLab® fingerprints were used to study the relatedness of isolates.

Results

Fourteen isolates co-expressing bla

CTX-M15, qnrB1, and aac(6′)-Ib-cr were identified. Genotypic analysis of these isolates identified 12 clonally related strains recovered from 10 patients. The increased prevalence of bla

CTX-M15-qnrB1-aac(6′)-Ib-cr-producing K. pneumoniae coincided with the presence in the ICU of a patient originally from Nigeria. This patient was infected by a strain not clonally related to the others but harbouring qnrB1 and aac(6′)-Ib-cr genes, a finding not hitherto observed in France. We suspected transmission of resistance plasmids followed by rapid dissemination of the multiresistant K. pneumoniae clone by cross-transmission.

Conclusion

This study highlights the importance of microbiological screening for multidrug-resistant strains in ICUs, particularly among patients from regions in which multidrug-resistant bacteria are known to exist.
How caregivers view patient comfort and what they do to improve it: a French survey
Authors: Lombardo Véronique , Vinatier Isabelle , Baillot Marie-Lou , Franja Vicenta , Bourgeon-Ghittori Irma , Dray Sandrine , Jeune Sylvie , Mossadegh Chirine , Reignier Jean , Souweine Bertrand , Roch Antoine ,   Société de Réanimation de Langue Française (SRLF)
Published: July 2013

Background

Intensive care unit (ICU) patients are exposed to many sources of discomfort. Most of these are related to the patient’s condition, but ICU design or how care is organized also can contribute. The present survey was designed to describe the opinions of ICU caregivers on sources of patient discomfort and to determine how they were dealt with in practice. The architectural and organizational characteristics of ICUs also were analyzed in relation to patient comfort.

Methods

An online, closed-ended questionnaire was developed. ICU caregivers registered at the French society of intensive care were invited to complete this questionnaire.

Results

A total of 915 staff members (55% nurses) from 264 adult and 28 pediatric ICUs completed the questionnaire. Analysis of the answers reveals that: 68% of ICUs had only single-occupancy rooms, and 66% had natural light in each room; ICU patients had access to television in 59% of ICUs; a clock was present in each room in 68% of ICUs. Visiting times were <4 h in 49% of adult ICUs, whereas 64% of respondents considered a 24-h policy to be very useful or essential to patients’ well-being. A nurse-driven analgesia protocol was available in 42% of units. For caregivers, the main sources of patient discomfort were anxiety, feelings of restraint, noise, and sleep disturbances. Paramedics generally considered discomfort related to thirst, lack of privacy, and the lack of space and time references, whereas almost 50% of doctors ignored these sources of discomfort. Half of caregivers indicated they assessed sleep quality. A minority of caregivers declared regular use of noise-reduction strategies. Twenty percent of respondents admitted to having non-work-related conversations during patient care, and only 40% indicated that care often was or always was provided without closing doors. Family participation in care was planned in very few adult ICUs.

Conclusions

Results of this survey showed that ICUs are poorly equipped to ensure patient privacy and rest. Access by loved ones and their participation in care also is limited. The data also highlighted that some sources of discomfort are less often taken into account by caregivers, despite being considered to contribute significantly.
Estimating long-run equilibrium real exchange rates: short-lived shocks with long-lived impacts on Pakistan
Authors: Zardad Asma , Mohsin Asma , Zaman Khalid
Published: July 2013

The purpose of this study is to investigate the factors that affect real exchange rate volatility for Pakistan through the co-integration and error correction model over a 30-year time period, i.e. between 1980 and 2010. The study employed the autoregressive conditional heteroskedasticity (ARCH), generalized autoregressive conditional heteroskedasticity (GARCH) and Vector Error Correction model (VECM) to estimate the changes in the volatility of real exchange rate series, while an error correction model was used to determine the short-run dynamics of the system. The study is limited to a few variables i.e., productivity differential (i.e., real GDP per capita relative to main trading partner); terms of trade; trade openness and government expenditures in order to manage robust data. The result indicates that real effective exchange rate (REER) has been volatile around its equilibrium level; while, the speed of adjustment is relatively slow. VECM results confirm long run convergence of real exchange rate towards its equilibrium level. Results from ARCH and GARCH estimation shows that real shocks volatility persists, so that shocks die out rather slowly, and lasting misalignment seems to have occurred.
Time spent on health related activity by older Australians with diabetes
Authors: Yen Laurann E , McRae Ian S , Jowsey Tanisha , Bagheri Nasser
Published: July 2013

Aims

There is little information available about what people do to look after their health, or how long people spend on health activities. This study identifies key health related activities and time taken as part of self management by people with diabetes. Management planning often lacks information that this study provides that would help clinicians and patients to create manageable and do-able plans that patients can follow.

Methods

Data were collected in 2010 using a national survey of people aged 50 years the National Diabetes Services Scheme. Respondents provided recall data on time used for personal health care, non-clinical health activity; and health service interactions. Data were analysed using Stata 12 and SPSS 19.

Results

While most people with diabetes spend on average less than 30 minutes a day on health-related activities (excluding exercise), the highest decile of respondents averaged over 100 minutes. Time spent increased with the number of co-existent conditions. Taking medication and sitting in waiting rooms were the most frequently reported activities. The greatest amount of time was spent on daily personal health care activities.

Conclusion

The time demands of diabetes for older people can be substantial. Better patient engagement in self management might result from a better match in care planning between the illness demands and the patient time availability, with potential to reduce admissions for hospital care.
Transcriptome analysis of human tissues and cell lines reveals one dominant transcript per gene
Authors: Gonzàlez-Porta Mar , Frankish Adam , Rung Johan , Harrow Jennifer , Brazma Alvis
Published: July 2013

Background

RNA sequencing has opened new avenues for the study of transcriptome composition. Significant evidence has accumulated showing that the human transcriptome contains in excess of a hundred thousand different transcripts. However, it is still not clear to what extent this diversity prevails when considering the relative abundances of different transcripts from the same gene.

Results

Here we show that, in a given condition, most protein coding genes have one major transcript expressed at significantly higher level than others, that in human tissues the major transcripts contribute almost 85 percent to the total mRNA from protein coding loci, and that often the same major transcript is expressed in many tissues. We detect a high degree of overlap between the set of major transcripts and a recently published set of alternatively spliced transcripts that are predicted to be translated utilizing proteomic data. Thus, we hypothesize that although some minor transcripts may play a functional role, the major ones are likely to be the main contributors to the proteome. However, we still detect a non-negligible fraction of protein coding genes for which the major transcript does not code a protein.

Conclusions

Overall, our findings suggest that the transcriptome from protein coding loci is dominated by one transcript per gene and that not all the transcripts that contribute to transcriptome diversity are equally likely to contribute to protein diversity. This observation can help to prioritize candidate targets in proteomics research and to predict the functional impact of the detected changes in variation studies.
What civilian psychiatrists should know about military psychiatry
Authors: Deahl Martin , Siddiquee Rehan
Published: July 2013

Few of us have first-hand experience of military psychiatry. However, as a result of recent conflict and the imminent downsizing of the armed forces we will almost certainly be seeing increasing numbers of ex-servicemen in our clinics. This paper explains what civilian mental health professionals should know when dealing with service and ex-service men and women.
Suicide prevention: are we doing enough?
Authors: Cole-King Alys , Parker Victoria , Williams Helen , Platt Stephen
Published: July 2013

Healthcare professionals require an understanding of how the behaviour and characteristics of both patients and assessors can affect suicide risk identification and response. This article reviews the literature on how we currently assess suicide risk and considers the need for a paradigm shift in how healthcare professionals engage with and assess suicidal patients. It also reviews some of the evidence base for interventions to mitigate the risk of suicide and promotes pragmatic and compassionate interventions.
New diagnostic concepts in Alzheimer's disease
Authors: Watkin Anna , Sikdar Sudip , Majumdar Biswadeep , Richman Anna V.
Published: July 2013

This article gives an overview of the profile of Alzheimer's disease, its pathophysiology and recent developments in technology that enable better understanding of the mechanism of disease. The diagnostic criteria and role of biomarkers proposed are explained. The new subgroups described are outlined in table form for easy reference. Subtypes of mild cognitive impairment (MCI) are reviewed and the conversion of amnestic MCI to Alzheimer's disease is considered. The implications and change to current clinical practice form the basis of the conclusion of the article.
Review of treatment for late-life depression
Authors: Allan Charlotte L. , Ebmeier Klaus P.
Published: July 2013

Depressive disorder in those over the age of 60 has many clinical similarities to depression in younger adults, but biological changes related to ageing may necessitate a different approach to treatment. We present an evidence-based review of treatment for late-life depression, focusing on pharmacological approaches, including monotherapy, combination and augmentation strategies. Selective serotonin reuptake inhibitors such as sertraline and citalopram are well tolerated, have the advantage of a favourable side-effect profile, and are good options for first-line treatment. Second-line treatment options include combination therapy with a second antidepressant, or treatment augmentation with an antipsychotic or lithium. We also consider evidence for nonpharmacological treatment strategies, including psychological therapy and neurostimulation. Finally, we summarise evidence for treatment of depression in patients in dementia.
Serotonin – 100 words
Authors: Cowen Philip J.
Published: July 2013

Serotonin is a neurotransmitter conserved through at least 500 million years of nervous system evolution. Serotonin orchestrates adaptive responses to aversive stimuli in invertebrates and an analogous role can be discerned in the more complex behavioural repertoire displayed by mammals to adversity. However, this formulation fails to capture the range of human social behaviours influenced by serotonin, for example, affiliation, empathy and cooperation. In a psychopharmacology experiment I received paroxetine for three weeks. This boost in brain serotonin levels failed to alter my subjective ratings of mood and anxiety. My wife felt differently; ‘Can't you stay on it?’, she said.
Socioeconomic status as a risk factor for dementia death: individual participant meta-analysis of 86 508 men and women from the UK
Authors: Russ Tom C. , Stamatakis Emmanuel , Hamer Mark , Starr John M. , Kivimäki Mika , Batty G. David
Published: July 2013

Background

Life-course socioeconomic factors may have a role in dementia aetiology but there is a current paucity of studies. Meta-analyses of individual participant data would considerably strengthen this evidence base.

Aims

To examine the association between socioeconomic status in early life and adulthood with later dementia death.

Method

Individual participant meta-analysis of 11 prospective cohort studies (1994–2004,n= 86508).

Results

Leaving full-time education at an earlier age was associated with an increased risk of dementia death in women (fully adjusted hazard ratio (HR) for age ⩽14v.age ⩾16: HR = 1.76, 95% Cl 1.23–2.53) but not men. Occupational social class was not statistically significantly associated with dementia death in men or women.

Conclusions

Lower educational attainment in women was associated with an increased risk of dementia-related death independently of common risk behaviours and comorbidities.
Tardive dyskinesia in schizophrenia
Authors: Liddle Peter F.
Published: July 2013

Sarró et al report grey matter deficits associated with tardive dyskinesia in schizophrenia. Much evidence suggests that the intrinsic pathophysiology of schizophrenia contributes to predisposition to tardive dyskinesia. The possibility that antipsychotics might play a causal role in the grey matter deficits cannot be excluded, but the evidence is tenuous.
Crisis teams: systematic review of their effectiveness in practice
Authors: Carpenter Rebecca A. , Falkenburg Jara , White Thomas P. , Tracy Derek K.
Published: July 2013

Aims and method

Crisis resolution and home treatment teams (variously abbreviated to CRTs, CRHTTs, HTTs) were introduced to reduce the number and duration of in-patient admissions and better manage individuals in crisis. Despite their ubiquity, their evidence base is challengeable. This systematic review explored whether CRTs: (a) affected voluntary and compulsory admissions; (b) treat particular patient groups; (c) are cost-effective; and (d) provide care patients value.

Results

Crisis resolution teams appear effective in reducing admissions, although data are mixed and other factors have also influenced this. Compulsory admissions may have increased, but evidence that CRTs are causally related is inconclusive. There are few clinical differences between ‘gate-kept’ patients admitted and those not. Crisis resolution teams are cheaper than in-patient care and, overall, patients are satisfied with CRT care.

Clinical implications

High-quality evidence for CRTs is scarce, although they appear to contribute to reducing admissions. Patient-relevant psychosocial and longitudinal outcomes are under-explored.