bluuebunny/crossref_metadata_2025 huggingface dataset:
Stepped care targeting psychological distress in head and neck and lung cancer patients: a randomized clinical trial
Authors: Krebber Anne-Marie H , Leemans C René , de Bree Remco , van Straten Annemieke , Smit Filip , Smit Egbert F , Becker Annemarie , Eeckhout Guus M , Beekman Aartjan TF , Cuijpers Pim , Leeuw Irma M Verdonck-de
Published: May 2012

Background

Psychological distress is common in cancer survivors. Although there is some evidence on effectiveness of psychosocial care in distressed cancer patients, referral rate is low. Lack of adequate screening instruments in oncology settings and insufficient availability of traditional models of psychosocial care are the main barriers. A stepped care approach has the potential to improve the efficiency of psychosocial care. The aim of the study described herein is to evaluate efficacy of a stepped care strategy targeting psychological distress in cancer survivors.

Methods/design

The study is designed as a randomized clinical trial with 2 treatment arms: a stepped care intervention programme versus care as usual. Patients treated for head and neck cancer (HNC) or lung cancer (LC) are screened for distress using OncoQuest, a computerized touchscreen system. After stratification for tumour (HNC vs. LC) and stage (stage I/II vs. III/IV), 176 distressed patients are randomly assigned to the intervention or control group. Patients in the intervention group will follow a stepped care model with 4 evidence based steps: 1. Watchful waiting, 2. Guided self-help via Internet or a booklet, 3. Problem Solving Treatment administered by a specialized nurse, and 4. Specialized psychological intervention or antidepressant medication. In the control group, patients receive care as usual which most often is a single interview or referral to specialized intervention. Primary outcome is the Hospital Anxiety and Depression Scale (HADS). Secondary outcome measures are a clinical level of depression or anxiety (CIDI), quality of life (EQ-5D, EORTC QLQ-C30, QLQ-HN35, QLQ-LC13), patient satisfaction with care (EORTC QLQ-PATSAT), and costs (health care utilization and work loss (TIC-P and PRODISQ modules)). Outcomes are evaluated before and after intervention and at 3, 6, 9 and 12 months after intervention.

Discussion

Stepped care is a system of delivering and monitoring treatments, such that effective, yet least resource-intensive, treatment is delivered to patients first. The main aim of a stepped care approach is to simplify the patient pathway, provide access to more patients and to improve patient well-being and cost reduction by directing, where appropriate, patients to low cost (self-)management before high cost specialist services.

Trial registration

NTR1868
The effects of knee arthroplasty on walking speed: A meta-analysis
Authors: Abbasi-Bafghi Hamid , Fallah-Yakhdani Hamid R , Meijer Onno G , de Vet Henrica CW , Bruijn Sjoerd M , Yang Li-Yong , Knol Dirk L , Van Royen Barend J , van Dieën Jaap H
Published: May 2012

Background

Patients with knee osteoarthritis patients have problems with walking, and tend to walk slower. An important aim of knee arthroplasty is functional recovery, which should include a post-operative increase in walking speed. Still, there are several problems with measuring walking speed in groups of knee osteoarthritis patients. Nevertheless, test-retest reliability of walking speed measurements is high, and when the same investigators monitor the same subjects, it should be possible to assess the walking speed effects of knee arthroplasty. The present study reports a meta-analysis of these effects.

Methods

A total of 16 independent pre-post arthroplasty comparisons of walking speed were identified through MEDLINE, Web of Science, and PEDro, in 12 papers, involving 419 patients.

Results

For 0.5–5 months post-operatively, heterogeneity was too large to obtain a valid estimate of the overall effect-size. For 6–12 and 13–60 months post-operatively, heterogeneity was absent, low, or moderate (depending on estimated pre-post correlations). During these periods, subjects walked on average 0.8 standard-deviations faster than pre-operatively, which is a large effect. Meta-regression analysis revealed significant effects of time and time squared, suggesting initial improvement followed by decline.

Conclusion

This meta-analysis revealed a large effect of arthroplasty on walking speed 6–60 months post-operatively. For the first 0.5–5 months, heterogeneity of effect-sizes precluded a valid estimate of short-term effects. Hence, patients may expect a considerable improvement of their walking speed, which, however, may take several months to occur. Meta-regression analysis suggested a small decline from 13 months post-operatively onwards.
Half forehead reconstruction with a single rotational scalp flap for dermatofibrosarcoma protuberans treatment
Authors: Mori Stefano , Di Monta Gianluca , Marone Ugo , Chiofalo Maria Grazia , Caracò Corrado
Published: May 2012

Background

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate to low-grade malignancy. Although metastasis rarely occurs, DFSP has a locally aggressive behavior with a high recurrence rate. In the head and neck area, resection involving a wide margin of healthy tissue can be difficult because of functional and cosmetic considerations. We describe a novel reconstructive method for half forehead defects with an innovative single local wide scalp flap following excision of DFSP with a 3 cm margin of healthy tissue.

Methods

Two patients underwent wide resection of forehead DFSP and reconstruction with a single rotational scalp flap. The scalp flap blood supply was provided from three main vessels: the superficial temporal artery, occipital artery and posterior auricular artery.

Results

No early or late complications were observed in either patient with no local recurrence after 18 months of follow-up. The donor area could be closed primarily in both cases and the flaps survived completely.

Conclusion

This innovative technique allowed a radical excision of forehead DFSP with sufficient healthy margins, thus potentially decreasing tumor recurrence rate. Reconstruction was achieved avoiding microsurgery, skin expanders and large skin grafts. Moreover, all main reconstructive criteria, such as functional and cosmetic tissue characteristics, were completely fulfilled.
The FSH-inhibin axis in prader-willi syndrome: heterogeneity of gonadal dysfunction
Authors: Gross-Tsur Varda , Hirsch Harry J , Benarroch Fortu , Eldar-Geva Talia
Published: May 2012

Background

We characterized the spectrum and etiology of hypogonadism in a cohort of Prader-Willi syndrome (PWS) adolescents and adults.

Methods

Reproductive hormonal profiles and physical examination were performed on 19 males and 16 females ages 16–34 years with PWS. Gonadotropins, sex-steroids, inhibin B (INB) and anti-Mullerian hormone (AMH) were measured. We defined 4 groups according to the relative contribution of central and gonadal dysfunction based on FSH and INB levels: Group A: primary hypogonadism (FSH >15 IU/l and undetectable INB (<10 pg/ml); Group B: central hypogonadism (FSH <0.5 IU/l, INB <10 pg/ml); Group C: partial gonadal & central dysfunction (FSH 1.5–15 IU/l, INB >20 pg/ml); Group D: mild central and severe gonadal dysfunction (FSH 1.5–15 IU/l, INB < 10 pg/ml.

Results

There were 10, 8, 9 and 8 individuals in Groups A-D respectively; significantly more males in group A (9, 4, 4 and 2; P = 0.04). Significant differences between the groups were found in mean testosterone (P = 0.04), AMH (P = 0.003) and pubic hair (P = 0.04) in males and mean LH (P = 0.003) and breast development (P = 0.04) in females. Mean age, height, weight, BMI and the distribution of genetic subtypes were similar within the groups.

Conclusions

Analysis of FSH and inhibin B revealed four distinct phenotypes ranging from primary gonadal to central hypogonadism. Primary gonadal dysfunction was common, while severe gonadotropin deficiency was rare. Longitudinal studies are needed to verify whether the individual phenotypes are consistent.
P2P and grid computing: opportunity for building next generation wireless multimedia digital library
Authors: Arulanandam Srinivasan , Jaganathan Suresh , Avula Damodaram
Published: May 2012

Nowadays digital libraries have become the source of information, sharing across the globe in the fields of education, research and knowledge. The full usage of digital libraries will be realized only when people can have access to the material from any location. The advantage of multimedia is that people of all ages can understand more clearly by seeing or hearing rather than reading. Considering the exponential growth in various technologies, developing a multimedia digital library in wireless is not an complicated task. Grid computing enables the virtualization data resources, process network bandwidth and storage capacities to create a single system image granting the user a seamless access to vast IT capabilities. By adopting peer-to-peer overlay networks, which are taking a central position in information systems, the storage space problem can be solved and by using grid computing the security can be maintained. In this article, we propose a framework for wireless multimedia digital library, built using Grid and P2P technology. Using this proposed framework, the digital data is stored in a cluster built of commodity components and users can access those data from anywhere, anytime securely. Advantages of this framework are: (i) existing capital investments are used for storing the multimedia files, (ii) increased access to data, (iii) balancing workloads among different systems connected in pGrid nodes, (iv) authenticated and secured transfer of files. Benchmarks used to test this framework are: (i) file size vs. download time, (ii) simultaneous connections, (iii) band-width utilization, (iv) security, (v) scalability, and (vi) robustness.
A new integral transform on time scales and its applications
Authors: Agwa Hassan Ahmed , Ali Fatma Mohamed , Kılıçman Adem
Published: May 2012

Integral transform methods are widely used to solve the several dynamic equations with initial values or boundary conditions which are represented by integral equations. With this purpose, the Sumudu transform is introduced in this article as a new integral transform on a time scale "Equation missing" to solve a system of dynamic equations. The Sumudu transform on time scale "Equation missing" has not been presented before. The results in this article not only can be applied on ordinary differential equations when

T
=
ℝ

, difference equations when

T
=

ℕ

0

, but also, can be applied for q-difference equations when

T
=

q

ℕ

0

, where

q

ℕ

0

:
=

{

q

t

:
t
∈

ℕ

0

 for 
q
>
1

}

or

T
=

q

ℤ

¯

:
=

q

ℤ

∪

{

0

}

for q > 1 (which has important applications in quantum theory) and on different types of time scales like

T
=
h

ℕ

0

,

T
=

ℕ

0

2

and

T
=

T

n

the space of the harmonic numbers. Finally, we give some applications to illustrate our main results.

2010 Mathematics Subject Classification. 44A85; 35G15; 44A35.
The gamma-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens
Authors: Fu Zhenyu , Yang Hongfa , Xiao Yuqiang , Zhao Gang , Huang Haiyan
Published: May 2012

Background

Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear.

Methods

We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo.

Results

The present study demonstrated that morphine challenge (3 mg/kg, s.c.) obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg) significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge.

Conclusions

Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.
Proposal for a recovery prediction method for patients affected by acute mediastinitis
Authors: Jabłoński Sławomir , Kozakiewicz Marcin
Published: May 2012

Background

An attempt to find a prediction method of death risk in patients affected by acute mediastinitis. There is not such a tool described in available literature for that serious disease.

Methods

The study comprised 44 consecutive cases of acute mediastinitis. General anamnesis and biochemical data were included. Factor analysis was used to extract the risk characteristic for the patients. The most valuable results were obtained for 8 parameters which were selected for further statistical analysis (all collected during few hours after admission). Three factors reached Eigenvalue >1. Clinical explanations of these combined statistical factors are: Factor1 - proteinic status (serum total protein, albumin, and hemoglobin level), Factor2 - inflammatory status (white blood cells, CRP, procalcitonin), and Factor3 - general risk (age, number of coexisting diseases). Threshold values of prediction factors were estimated by means of statistical analysis (factor analysis, Statgraphics Centurion XVI).

Results

The final prediction result for the patients is constructed as simultaneous evaluation of all factor scores. High probability of death should be predicted if factor 1 value decreases with simultaneous increase of factors 2 and 3. The diagnostic power of the proposed method was revealed to be high [sensitivity =90%, specificity =64%], for Factor1 [SNC = 87%, SPC = 79%]; for Factor2 [SNC = 87%, SPC = 50%] and for Factor3 [SNC = 73%, SPC = 71%].

Conclusion

The proposed prediction method seems a useful emergency signal during acute mediastinitis control in affected patients.
Conception rate, uterine infection and embryo quality after artificial insemination and natural breeding with a stallion carrier of Pseudomonas aeruginosa: a case report
Authors: Tiago Guimarães , Júlio Carvalheira , António Rocha
Published: May 2012

Background

Pseudomonas aeruginosa may cause venereal disease and infertility in horses. A Pseudomonas aeruginosa - carrier stallion, often unresponsive to artificial vagina collection, was used to naturally breed mares. Semen collected from the same stallion was also used to perform artificial inseminations. Pregnancy rates, embryo quality and incidence of uterine infection were compared between inseminated or naturally-bred mares.

Methods

P. aeruginosa was isolated from swabbing of the penis, prepuce and distal urethra of the stallion. Before being bred or inseminated, clitoral/vestibular samples were collected from all mares, and cultured for isolation of P. aeruginosa. At the first observed estrus, endometrial swabs were also collected. All mares subjected to natural mating (NS) were re-evaluated for P.aeruginosa by culture of clitoral and endometrial swabs. Artificial inseminations (AI) were performed either with fresh-extended semen (11 AI/7 mares) or frozen semen (10 AI/7 mares). The stallion was also used to breed 3 mares (4 services). For embryo collection, 2 mares were inseminated with fresh-extended semen (1 AI/mare), and 2 additional mares were inseminated with frozen semen (2 AI/mare). Two mares were naturally-bred with a total of 9 services, for embryo collection. All mares were examined after AI or natural service (NS), for uterine pathologies. Embryo recoveries were attempted passing a catheter with inflatable cuff connected to a sterile flexible 2-way flushing catheter, through the cervix. Flushed media was recovered into an Em-Con filter, and embryos searched using a stereoscope. Embryos were graded from 1 (excellent) to 4 (degenerated/dead).

Results

Pregnancy rates obtained after NS was 50% per cycle. However, more than half of the NS resulted in uterine disease, while uterine pathology was seen only in 22% of the time following AI. Half of the mares bred by NS got positive to P. aeruginosa. Percentage of embryo recovery rates was identical after AI or NS (66.7%). The 4 embryos recovered after AI were classified as Grade 1, while after NS only 2 out of the 6 recovered embryos were Grade 1.

Conclusion

a) there was no evidence of reduced fertilization after AI or NS, b) a numerically higher incidence of uterine disease was noticed after NS, c) venereal transmission of P. aeruginosa after NS was confirmed, d) a lower percentage of G1 embryos may be obtained after NS. Overall, the data supports the indication for P. aeruginosa-carrier stallions to be bred by AI rather than by NS, and raises the possibility that P. aeruginosa may affect embryo quality.
A patient with bacteraemia and possible endocarditis caused by a recently-discovered genomospecies of Capnocytophaga: Capnocytophaga genomospecies AHN8471: a case report
Authors: Mills Jonathan M , Lofthouse Emma , Roberts Phil , Karas Johannis A
Published: May 2012

Introduction

Capnocytophaga are a genus of bacteria that have been found to be the causative organisms in a range of infections, including serious conditions such as bacteraemia, endocarditis and meningitis. This has been especially true amongst those with serious comorbidities and the immunocompromised populations. Although several species are known to cause human disease, historically, laboratories have often not identified isolates to species level due to the unreliable, laborious techniques needed. With the advent of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism Analysis, identification to species level is now frequently possible and desirable, as it may provide clues as to the source of infection and its treatment.

Case presentation

Here we describe a case of bacteraemia and possible endocarditis in a 64-year-old white British man caused by a newly identified genomospecies of Capnocytophaga in a patient subsequently diagnosed with metastatic adenocarcinoma of the oesophagus. The source of the bacteraemia was presumed to be from the patient's own oral flora.

Conclusion

Our case further confirms the potential for Capnocytophaga to cause systemic infections, highlights the availability and need for identification of isolates to species level and re-emphasises the difficulty in diagnosing Capnocytophaga infections due to their slow growth in the laboratory.
Stiff person syndrome presenting with sudden onset of shortness of breath and difficulty moving the right arm: a case report
Authors: Goodson Bradley , Martin Kate , Hunt Thomas
Published: May 2012

Introduction

First described in 1956, stiff person syndrome is characterized by episodes of slowly progressive stiffness and rigidity in both the paraspinal and limb muscles. Although considered a rare disorder, stiff person syndrome is likely to be under-diagnosed due to a general lack of awareness of the disease in the medical community.

Case presentation

A 27-year-old Hispanic woman presented to our emergency department with a sudden onset of shortness of breath and difficulty moving her right arm. Her physical examination was remarkable in that her abdomen was firm to palpation and her right upper extremity was rigid on passive and active ranges of motion. Her right fingers were clenched in a fist. Her electromyography findings were consistent with stiff person syndrome in the right clinical setting. Stiff person syndrome is confirmed by testing for the anti-glutamic acid decarboxylase antibody. Her test for this was positive.

Conclusion

Stiff person syndrome may not be a common condition. However, if disregarded in the differential diagnosis, it can lead to several unnecessary tests being carried out causing a delay in treatment. This case report reveals some of the characteristic features of stiff person syndrome with an atypical presentation.
Squamous cell carcinoma of rectum presenting in a man: a case report
Authors: Sameer A Syed , Syeed Nidda , Chowdri Nissar A , Parray Fazl Q , Siddiqi Mushtaq A
Published: May 2012

Background

Primary squamous cell carcinomas of the colorectum are very uncommon. Until now, to the best of our knowledge, only 114 cases of squamous cell carcinoma in the colorectum exist in the reported literature. Here we report a case of squamous cell carcinoma of the rectum in the ethnic Kashmiri population in northern India.

Case Presentation

The case of a 60-year-old male patient (Asian) with a pure squamous cell carcinoma of the rectum is presented here. The patient underwent a curative surgery with concomitant chemotherapy. Two years after the initial curative resection of the tumor he is still alive.

Conclusion

The prognosis for squamous cell carcinoma of the colorectum is worse than for that of adenocarcinoma, because of the delayed diagnosis. The etiopathogenicity of squamous cell carcinoma of the colorectum is discussed. Surgical resection of the lesion seems to be the treatment of choice. Chemotherapy also helps in improvement of the prognosis.
Elevation of dopamine level reduces host-seeking activity in the adult female mosquito Aedes albopictus
Authors: Fukumitsu Yuki , Irie Keiichi , Satho Tomomitsu , Aonuma Hitoshi , Dieng Hamady , Ahmad Abu Hassan , Nakashima Yukihiko , Mishima Kenichi , Kashige Nobuhiro , Miake Fumio
Published: May 2012

Background

Mosquito-borne viruses are transmitted to human hosts via blood-feeding behavior of female mosquitoes. Female mosquitoes seek a host to take blood meals (host-seeking behavior). In order to prevent virus infections, it is important to understand how they modulate host-seeking behavior. Dopamine (DA) in the central nervous system acts as a neuromediator that regulates a variety of behaviors in insects. In female mosquitoes, host-seeking behavior increases when DA levels in the head decline after emergence. However, it remains unclear whether DA directly modulates host-seeking behavior in female mosquitoes. The aim of this study was to examine whether changes in DA levels in the head affects host-seeking activity in the adult female mosquito Aedes albopictus (Ae. albopictus).

Findings

We compared host-seeking behavior in one group of emerging female adults treated with l-β-3,4-dihydroxyphenylalanine (l-DOPA), the precursor of DA, (l-DOPA group), with that in an untreated control (control group) after confirming elevation of head DA in l-DOPA group by using high-performance liquid chromatography. The content of head DA in l-DOPA group significantly remained higher than that in controls on all days examined. The host-seeking activity in the control group showed a gradual increase over the 6-day experimental period. In contrast, there was no such increase in the host-seeking activity in the l-DOPA group. Therefore, the host-seeking activity of l-DOPA group was significantly lower than that of the controls between day 3 and 6 post-emergence.

Conclusion

Our results indicate that elevation of DA level reduces host-seeking activity in adult female mosquito Ae. albopictus.
Genome wide analysis and clinical correlation of chromosomal and transcriptional mutations in cancers of the biliary tract
Authors: Miller George , Socci Nicholas D , Dhall Deepti , D'Angelica Michael , DeMatteo Ronald P , Allen Peter J , Singh Bhuvanesh , Fong Yuman , Blumgart Leslie H , Klimstra David S , Jarnagin William R
Published: May 2012

Background

The pathogenesis of biliary cancers is ill-defined. This study investigates changes in gene expression and copy number in biliary cancers and correlates these changes with anatomical site of origin, histopathology and outcome.

Methods

We performed gene expression and CGH analysis on 34 biliary tract cancer specimens. Results were confirmed by RT-PCR. Clinical-pathologic correlation was made using functional over-representation analysis of the top 100 mutations associated with each variable.

Results

There were 545 genes with altered expression in extrahepatic cholangiocarcinoma, 2,354 in intrahepatic cholangiocarcinoma, and 1,281 in gallbladder cancer. Unsupervised hierarchical clustering analysis indicated there was no difference in the global gene expression patterns between each biliary cancer subgroup. CGH analysis revealed that short segments of chromosomes 1p, 3p, 6q, 8p, 9p, and 14q were commonly deleted across all cancer subtypes. Commonly amplified regions included segments of 1q, 3q, 5p, 7p, 7q, 8q, and 20q. Over-representation analysis revealed an association between altered expression of functional gene groupings and pathologic features.

Conclusion

This study defined regions of the genome associated with changes in DNA copy number and gene expression in specific subtypes of biliary cancers. The findings have implications for identification of therapeutic targets, screening, and prognostication.
Synergistic effect of simvastatin and ezetimibe on lipid and pro-inflammatory profiles in pre-diabetic subjects
Authors: Kater Ana-Lucia A , Batista Marcelo C , Ferreira Sandra RG
Published: May 2012

Background

Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol and plant sterols. Synergism of ezetimibe-statin therapy on LDL-cholesterol has been demonstrated, but data concerning the pleiotropic effects of this combination are controversial.

Objective

This open-label trial evaluated whether the combination of simvastatin and ezetimibe also results in a synergistic effect that reduces the pro-inflammatory status of pre-diabetic subjects.

Methods

Fifty pre-diabetic subjects were randomly assigned to one of 2 groups, one receiving ezetimibe (10 mg/day), the other, simvastatin (20 mg/d) for 12 weeks, followed by an additional 12-week period of combined therapy. Blood samples were collected at baseline, 12 and 24 weeks. RESULTS: Total cholesterol, LDL-cholesterol and apolipoprotein B levels decreased in all the periods analyzed (p < 0.01), but triglycerides declined significantly only after combined therapy. Both drugs induced reductions in C-reactive protein, reaching statistical significance after combining ezetimibe with the simvastatin therapy (baseline 0.59 ± 0.14, simvastatin monotherapy 0.48 ± 0.12 mg/dL and 0.35 ± 0.12 mg/dL, p < 0.023). Such a reduction was independent of LDL-cholesterol change. However, mean levels of TNF-α and interleukin-6 and leukocyte count did not vary during the whole study.

Conclusion

Expected synergistic lowering effects of a simvastatin and ezetimibe combination on LDL-cholesterol, apolipoprotein B and triglycerides levels were confirmed in subjects with early disturbances of glucose metabolism. We suggest an additive effect of this combination also on inflammatory status based on the reduction of C-reactive protein. Attenuation of pro-inflammatory conditions may be relevant in reducing cardiometabolic risk.

Title/ID of trial registration

Effect of simvastatin and ezetimibe on lipid and inflammation/NCT01103648.
Naturally occurring variations in sequence length creates microRNA isoforms that differ in argonaute effector complex specificity
Authors: Ebhardt H Alexander , Fedynak Amber , Fahlman Richard P
Published: May 2012

Background

Micro(mi)RNAs are short RNA sequences, ranging from 16 to 35 nucleotides (miRBase; http://www.mirbase.org). The majority of the identified sequences are 21 or 22 nucleotides in length. Despite the range of sequence lengths for different miRNAs, individual miRNAs were thought to have a specific sequence of a particular length. A recent report describing a longer variant of a previously identified miRNA in Arabidopsis thaliana prompted this investigation for variations in the length of other miRNAs.

Results

In this paper, we demonstrate that a fifth of annotated A. thaliana miRNAs recorded in miRBase V.14 have stable miRNA isoforms that are one or two nucleotides longer than their respective recorded miRNA. Further, we demonstrate that miRNA isoforms are co-expressed and often show differential argonaute complex association. We postulate that these extensions are caused by differential cleavage of the parent precursor miRNA.

Conclusions

Our systematic analysis of A. thaliana miRNAs reveals that miRNA length isoforms are relatively common. This finding not only has implications for miRBase and miRNA annotation, but also extends to miRNA validation experiments and miRNA localization studies. Further, we predict that miRNA isoforms are present in other plant species also.
Case Report: Familial Gastric Cancer and Chordoma in the Same Family
Authors: Weber Walter , Scott Rodney J.
Published: May 2012

Gastric cancers are the second most common malignancy in the world and represent a major burden to all societies even though the incidence of disease is decreasing in the industrialized world. The aetiology of the disease is complex and is believed to be primarily due to environmental factors but a small proportion of cases are recognised as being associated with genetic factors. Two inherited forms of stomach cancer have been identified, one which is associated with familial clusterings of stomach cancer and the other being a subgroup of families that belong to hereditary non polyposis colorectal cancer (or Lynch syndrome). In this report we present a small nuclear family which is unusual in that there is a clustering of malignancy which includes stomach cancer, colorectal cancer and chordoma. Genetic analysis failed to reveal any causative mutation in genes associated with HNPCC or in E-cadherin. Together, the clinical picture in this family may indicate that other genetic factors are behind this family's clustering of malignancy.
Patient Perspective on the Value of Genetic Counselling for Familial Pancreas Cancer
Authors: Axilbund Jennifer E. , Brune Kieran A. , Canto Marcia I. , Brehon Brenda C , Wroblewski Lori D. , Griffin Constance A.
Published: May 2012

Purpose

To assess patient views regarding the value of genetic counselling for familial pancreas cancer in the absence of predictive genetic testing.

Patients and methods

At-risk adults with three or more relatives with pancreas cancer received genetic counselling prior to research screening via endoscopic ultrasound. Questionnaires were mailed after the visit to assess perceived value of the counselling session.

Results

Ninety-three percent of respondents felt genetic counselling for pancreas cancer was helpful despite the lack of a causative gene, while only 7% felt that it should not be offered until such a gene is discovered. Over half of respondents believed the pancreas cancer in their family was caused by a gene mutation, and 42% thought they had inherited the mutation. The average perceived lifetime risk of developing pancreas cancer was 51%, and 87% of respondents would ultimately seek predictive genetic testing. When more information is gained, 89% would be interested in another genetic counselling session, and 82% would recommend current genetic counselling for pancreas cancer to a friend or relative with a family history of the disease.

Conclusion

Despite the lack of an identified major causative gene for pancreas cancer, respondents found genetic counselling for this malignancy to be helpful. These patients perceive their personal cancer risk to be high, and would seek predictive genetic testing if it were available. Referral for genetic counselling should be offered to appropriate individuals.
Familial Adenomatous Polyposis: Experience from a Study of 1164 Unrelated German Polyposis Patients
Authors: Friedl Waltraut , Aretz Stefan
Published: May 2012

The autosomal-dominant precancerous condition familial adenomatous polyposis (FAP) is caused by germline mutations in the tumour suppressor gene APC. Consistent correlations between the site of mutations in the gene and clinical phenotype have been published for different patient groups. We report our experiences of APC mutation analysis and genotype-phenotype correlations in 1166 unrelated polyposis families and discuss our results in the light of literature data. We show that the mutation detection rates largely depend on the family history and clinical course of the disease. We present a list of 315 different point mutations and 37 large deletions detected in 634 of the 1166 index patients. Our results confirm previously published genotype-phenotype correlations with respect to the colorectal phenotype and extracolonic manifestations. However, 'exceptions to the rule' are also observed, and possible explanations for this are discussed. The discovery of autosomal-recessive MUTYH-associated polyposis (MAP) as a differential diagnosis to FAP implies that some results have to be reinterpreted and surveillance guidelines in the families have to be reevaluated.
Organization and Running of the First Comprehensive Hereditary Cancer Clinic in India
Authors: Rajkumar T , Soumittra N , Vidubala E , Sridevi V , Mahajan V , Ramanan SG , Vijaya S
Published: May 2012

Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social issues relevant to the given population in running the Hereditary Cancer Clinic.
Genetic and Preventive Services for Hereditary Breast and Ovarian Cancer in the Czech Republic
Authors: Foretova Lenka , Petrakova Katarina , Palacova Marketa , Kalabova Renata , Navratilova Marie , Lukesova Miroslava , Vasickova Petra , Machackova Eva , Kleibl Zdenek , Pohlreich Petr
Published: May 2012

The majority of hereditary breast and ovarian cancers can be accounted for by germline mutations in the BRCA1 and BRCA2 genes. Genetic counselling and testing in high-risk patients in the Czech Republic began in 1997 in two centres (Masaryk Memorial Cancer Institute in Brno, MMCI, and the General University Hospital plus the First Faculty of Medicine, Charles University in Prague, 1FMUK). Health insurance covers testing in MMCI, whereas testing at 1FMUK is covered by research grants. The spectrum of mutations in the BRCA1 gene is similar in the Bohemian (western) and Moravian (eastern) regions of the country but the mutation spectrum observed in the BRCA2 gene is completely different. There are three BRCA1 gene mutations that are responsible for 69% and 70.4% of all BRCA1 mutations identified in women reporting to the Brno and Prague centres, respectively. The two most frequent mutations in the BRCA2 gene, which comprises 41.5% of all detected BRCA2 mutations in Brno, were not found in women tested in the Prague centre. The testing of BRCA1/BRCA2 or other possible predisposition genes for hereditary breast/ovarian cancer is determined by medical geneticists after genetic counselling. Predictive testing is offered to persons older than 18 years of age. Genetic counselling centres are easily accessible to all inhabitants in the country. Specialized preventive care is mostly organized by MMCI and the General University Hospital in Prague; however, some patients and their family members are under the care of other oncology departments and clinics. The quality of preventive care in different hospitals is currently being investigated.
Brain natriuretic peptide for prediction of mortality in patients with sepsis: a systematic review and meta-analysis
Authors: Wang Fei , Wu Youping , Tang Lu , Zhu Weimin , Chen Feng , Xu Tao , Bo Lulong , Li Jinbao , Deng Xiaoming
Published: May 2012

Introduction

Early identification of septic patients at high risk of dying remains a challenge. The prognostic role of brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) in septic patients remains controversial. The purpose of this systematic review and meta-analysis was to investigate the value of elevated BNP or NT-proBNP in predicting mortality in septic patients.

Methods

PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched (up to February 18, 2011). Studies were included if they had prospectively collected data on all-cause mortality in adult septic patients with either plasma BNP or NT-proBNP measurement. Studies that failed to construct a 2 × 2 table of results were excluded. Two authors independently determined the validity of included studies and extracted data.

Results

12 studies with a total of 1,865 patients were included. Elevated natriuretic peptides were significantly associated with increased risk of mortality (odds ratio (OR) 8.65, 95% confidence interval (CI) 4.94 to 15.13, P < 0.00001). The association was consistent for BNP (OR 10.44, 95% CI 4.99 to 21.58, P < 0.00001) and NT-proBNP (OR 6.62, 95% CI 2.68 to 16.34, P < 0.0001). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 79% (95% CI 75 to 83), 60% (95% CI 57 to 62), 2.27 (95% CI 1.83 to 2.81) and 0.32 (95% CI 0.22 to 0.46), respectively.

Conclusions

Our results suggested that an elevated BNP or NT-proBNP level may prove to be a powerful predictor of mortality in septic patients. Future larger and more adequately powered prospective studies are warranted to clarify the assay standardization, the optimal cut-off, and the prognostic value of BNPs in conjunction with other biomarkers.
Improved estimation of mineral and fluid volumetric concentrations from well logs in thinly bedded and invaded formations
Authors: Heidari Zoya , Torres-Verdín Carlos , Preeg William E.
Published: May 2012

Calculation of mineral and fluid volumetric concentrations from well logs is one of the most important outcomes of formation evaluation. Conventional estimation methods assume linear or quasi-linear relationships between volumetric concentrations of solid/fluid constituents and well logs. Experience shows, however, that the relationship between neutron porosity logs and mineral concentrations is generally nonlinear. More importantly, linear estimation methods do not explicitly account for shoulder-bed and/or invasion effects on well logs, nor do they account for differences in the volume of investigation of the measurements involved in the estimation. The latter deficiencies of linear estimation methods can cause appreciable errors in the calculation of porosity and hydrocarbon pore volume. We investigated three nonlinear inversion methods for assessment of volumetric concentrations of mineral and fluid constituents of rocks from multiple well logs. All three of these methods accounted for the general nonlinear relationship between well logs, mineral concentrations, and fluid saturations. The first method accounted for the combined effects of invasion and shoulder beds on well logs. The second method also accounted for shoulder-bed effects but was intended for cases where mud-filtrate invasion is negligible or radially deep. Finally, the third method was designed specifically for analysis of thick beds where mud-filtrate invasion is either negligible or radially deep. Numerical synthetic examples of application indicated that nonlinear inversion of multiple well logs is a reliable method to quantify complex mineral and fluid compositions in the presence of thin beds and invasion. Comparison of results against those obtained with conventional multimineral estimation methods confirmed the advantage of nonlinear inversion of multiple well logs in quantifying thinly bedded invaded formations with variable and complex lithology, such as those often encountered in carbonate formations.
Adjustment disorders in primary care: prevalence, recognition
and use of services
Authors: Fernández Anna , Mendive Juan M. , Salvador-Carulla Luis , Rubio-Valera María , Luciano Juan Vicente , Pinto-Meza Alejandra , Haro Josep Maria , Palao Diego J. , Bellón Juan A. , Serrano-Blanco Antoni ,   the DASMAP investigators
Published: May 2012

Background

Within the ICD and DSM review processes there is growing debate on the
future classification and status of adjustment disorders, even though
evidence on this clinical entity is scant, particularly outside
specialised care.

Aims

To estimate the prevalence of adjustment disorders in primary care; to
explore whether there are differences between primary care patients with
adjustment disorders and those with other mental disorders; and to
describe the recognition and treatment of adjustment disorders by general
practitioners (GPs).

Method

Participants were drawn from a cross-sectional survey of a representative
sample of 3815 patients from 77 primary healthcare centres in Catalonia.
The prevalence of current adjustment disorders and subtypes were assessed
face to face using the Structured Clinical Interview for DSM-IV Axis I
Disorders (SCID-I). Multilevel logistic regressions were conducted to
assess differences between adjustment disorders and other mental
disorders. Recognition and treatment of adjustment disorders by GPs were
assessed through a review of patients' computerised clinical
histories.

Results

The prevalence of adjustment disorders was 2.94%. Patients with
adjustment disorders had higher mental quality-of-life scores than
patients with major depressive disorder but lower than patients without
mental disorder. Self-perceived stress was also higher in adjustment
disorders compared with those with anxiety disorders and those without
mental disorder. Recognition of adjustment disorders by GPs was low: only
2 of the 110 cases identified using the SCID-I were detected by the GP.
Among those with adjustment disorders, 37% had at least one psychotropic
prescription.

Conclusions

Adjustment disorder shows a distinct profile as an intermediate category
between no mental disorder and affective disorders (depression and
anxiety disorders).
Crossveinless d is a vitellogenin-like lipoprotein that binds BMPs and HSPGs, and is required for normal BMP signaling in the Drosophila wing
Authors: Chen Jun , Honeyager Shawn M. , Schleede Justin , Avanesov Andrei , Laughon Allen , Blair Seth S.
Published: May 2012

The sensitivity of the posterior crossvein in the pupal wing of Drosophila to reductions in the levels and range of BMP signaling has been used to isolate and characterize novel regulators of this pathway. We show here that crossveinless d (cv-d) mutations, which disrupt BMP signaling during the development of the posterior crossvein, mutate a lipoprotein that is similar to the vitellogenins that comprise the major constituents of yolk in animal embryos. Cv-d is made in the liver-like fat body and other tissues, and can diffuse into the pupal wing via the hemolymph. Cv-d binds to the BMPs Dpp and Gbb through its Vg domain, and to heparan sulfate proteoglycans, which are well-known for their role in BMP movement and accumulation in the wing. Cv-d acts over a long range in vivo, and does not have BMP co-receptor-like activity in vitro. We suggest that, instead, it affects the range of BMP movement in the pupal wing, probably as part of a lipid-BMP-lipoprotein complex, similar to the role proposed for the apolipophorin lipid transport proteins in Hedgehog and Wnt movement.
Spatially distinct regulatory roles for gibberellins in the promotion of flowering of Arabidopsis under long photoperiods
Authors: Porri Aimone , Torti Stefano , Romera-Branchat Maida , Coupland George
Published: May 2012

The plant growth regulator gibberellin (GA) contributes to many developmental processes, including the transition to flowering. In Arabidopsis, GA promotes this transition most strongly under environmental conditions such as short days (SDs) when other regulatory pathways that promote flowering are not active. Under SDs, GAs activate transcription of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and LEAFY (LFY) at the shoot meristem, two genes encoding transcription factors involved in flowering. Here, the tissues in which GAs act to promote flowering were tested under different environmental conditions. The enzyme GIBBERELLIN 2 OXIDASE 7 (GA2ox7), which catabolizes active GAs, was overexpressed in most tissues from the viral CaMV 35S promoter, specifically in the vascular tissue from the SUCROSE TRANSPORTER 2 (SUC2) promoter or in the shoot apical meristem from the KNAT1 promoter. We find that under inductive long days (LDs), GAs are required in the vascular tissue to increase the levels of FLOWERING LOCUS T (FT) and TWIN SISTER OF FT (TSF) mRNAs, which encode a systemic signal transported from the leaves to the meristem during floral induction. Similarly, impairing GA signalling in the vascular tissue reduces FT and TSF mRNA levels and delays flowering. In the meristem under inductive LDs, GAs are not required to activate SOC1, as reported under SDs, but for subsequent steps in floral induction, including transcription of genes encoding SQUAMOSA PROMOTER BINDING PROMOTER LIKE (SPL) transcription factors. Thus, GA has important roles in promoting transcription of FT, TSF and SPL genes during floral induction in response to LDs, and these functions are spatially separated between the leaves and shoot meristem.
Retinoic acid-driven Hox1 is required in the epidermis for forming the otic/atrial placodes during ascidian metamorphosis
Authors: Sasakura Yasunori , Kanda Miyuki , Ikeda Taku , Horie Takeo , Kawai Narudo , Ogura Yosuke , Yoshida Reiko , Hozumi Akiko , Satoh Nori , Fujiwara Shigeki
Published: May 2012

Retinoic acid (RA)-mediated expression of the homeobox gene Hox1 is a hallmark of the chordate central nervous system (CNS). It has been suggested that the RA-Hox1 network also functions in the epidermal ectoderm of chordates. Here, we show that in the urochordate ascidian Ciona intestinalis, RA-Hox1 in the epidermal ectoderm is necessary for formation of the atrial siphon placode (ASP), a structure homologous to the vertebrate otic placode. Loss of Hox1 function resulted in loss of the ASP, which could be rescued by expressing Hox1 in the epidermis. As previous studies showed that RA directly upregulates Hox1 in the epidermis of Ciona larvae, we also examined the role of RA in ASP formation. We showed that abolishment of RA resulted in loss of the ASP, which could be rescued by forced expression of Hox1 in the epidermis. Our results suggest that RA-Hox1 in the epidermal ectoderm played a key role in the acquisition of the otic placode during chordate evolution.