bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel DSPPmutation causes dentinogenesis imperfecta type II in a large Mongolian family
Authors: Bai Haihua , Agula Hasi , Wu Qizhu , Zhou Wenyu , Sun Yujing , Qi Yue , Latu Suya , Chen Yujie , Mutu Jiri , Qiu Changchun
Published: February 2010

Background

Several studies have shown that the clinical phenotypes of dentinogenesis imperfecta type II (DGI-II) may be caused by mutations in dentin sialophosphoprotein (DSPP). However, no previous studies have documented the clinical phenotype and genetic basis of DGI-II in a Mongolian family from China.

Methods

We identified a large five-generation Mongolian family from China with DGI-II, comprising 64 living family members of whom 22 were affected. Linkage analysis of five polymorphic markers flanking DSPP gene was used to genotype the families and to construct the haplotypes of these families. All five DSPP exons including the intron-exon boundaries were PCR-amplified and sequenced in 48 members of this large family.

Results

All affected individuals showed discoloration and severe attrition of their teeth, with obliterated pulp chambers and without progressive high frequency hearing loss or skeletal abnormalities. No recombination was found at five polymorphic markers flanking DSPP in the family. Direct DNA sequencing identified a novel A→G transition mutation adjacent to the donor splicing site within intron 3 in all affected individuals but not in the unaffected family members and 50 unrelated Mongolian individuals.

Conclusion

This study identified a novel mutation (IVS3+3A→G) in DSPP, which caused DGI-II in a large Mongolian family. This expands the spectrum of mutations leading to DGI-II.
Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue
Authors: Antonov Janine , Popovici Vlad , Delorenzi Mauro , Wirapati Pratyaksha , Baltzer Anna , Oberli Andrea , Thürlimann Beat , Giobbie-Hurder Anita , Viale Giuseppe , Altermatt Hans Jörg , Aebi Stefan , Jaggi Rolf
Published: February 2010

Background

The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months.

Methods

RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8), the progesterone receptor (five genes, PGR_5), Her2 (two genes, HER2_2), and proliferation (ten genes, PRO_10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score.

Results

Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS) in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses.

Conclusions

Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in postmenopausal patients with estrogen receptor positive breast cancer.

Trial Registration

Current Controlled Trials: NCT00004205
Genetic analysis of patients with Fuchs endothelial corneal dystrophy in India
Authors: Hemadevi Boomiraj , Srinivasan Muthiah , Arunkumar Jambulingam , Prajna Namperumalsamy V , Sundaresan Periasamy
Published: February 2010

Background

Mutations in COL8A2 gene which encodes the collagen alpha-2 (VIII) chain have been identified in both familial and sporadic cases of Fuchs endothelial corneal dystrophy (FECD). Heterozygous mutations in the SLC4A11 gene are also known to cause late-onset FECD. Therefore we screened for COL8A2, SLC4A11 gene variants in Indian FECD patients.

Methods

Eighty patients with clinically diagnosed FECD and 100 age matched normal individuals were recruited. Genomic DNA was isolated from peripheral blood leukocytes. Mutations in COL8A2, SLC4A11 coding regions were screened using bi-directional sequencing. Fischer's exact test or Pearson's chi squared test were used to predict the statistical association of genotypes with the phenotype.

Results

Screening of COL8A2 gene revealed 2 novel c.1610G>A, c.1643A>G and 3 reported variations c.112G>A, c.464G>A and c.1485G>A. In SLC4A11 gene, novel c.1659C>T, c.1974C>T and reported c.405G>A, c.481A>C and c.639G>A variants were identified. However all the variations in both the genes were also present in unaffected controls.

Conclusions

This is the first study analysing COL8A2 gene in Indian patients with FECD. No pathogenic mutations were identified in COL8A2. Merely silent changes, which showed statistically insignificant association with FECD, were identified in the screening of SLC4A11 gene. These results suggest that COL8A2, SLC4A11 genes may not be responsible for FECD in patients examined in this study.
Documentation of best interest by intensivists: a retrospective study in an Ontario critical care unit
Authors: Ratnapalan Mohana , Cooper Andrew B , Scales Damon C , Pinto Ruxandra
Published: February 2010

Background

Intensive care physicians often must rely on substitute decision makers to address all dimensions of the construct of "best interest" for incapable, critically ill patients. This task involves identifying prior wishes and to facilitate the substitute decision maker's understanding of the incapable patient's condition and their likely response to treatment. We sought to determine how well such discussions are documented in a typical intensive care unit.

Methods

Using a quality of communication instrument developed from a literature search and expert opinion, 2 investigators transcribed and analyzed 260 handwritten communications for 105 critically ill patients who died in the intensive care unit between January and June 2006. Cohen's kappa was calculated before analysis and then disagreements were resolved by consensus. We report results on a per-patient basis to represent documented communication as a process leading up to the time of death in the ICU. We report frequencies and percentages for discrete data, median (m) and interquartile range (IQR) for continuous data.

Results

Our cohort was elderly (m 72, IQR 58-81 years) and had high APACHE II scores predictive of a high probability of death (m 28, IQR 23-36). Length of stay in the intensive care unit prior to death was short (m 2, IQR 1-5 days), and withdrawal of life support preceded death for more than half (n 57, 54%). Brain death criteria were present for 18 patients (17%). Although intensivists' communications were timely (median 17 h from admission to critical care), the person consenting on behalf of the incapable patient was explicitly documented for only 10% of patients. Life support strategies at the time of communication were noted in 45% of charts, and options for their future use were presented in 88%. Considerations relevant to determining the patient's best interest in relation to the treatment plan were not well documented. While explicit survival estimates were noted in 50% of charts, physicians infrequently documented their own predictions of the patient's functional status (20%), anticipated need for chronic care (0%), or post ICU quality of life (3%). Similarly, documentation of the patient's own perspectives on these ranged from 2-18%.

Conclusions

Intensivists' documentation of their communication with substitute decision makers frequently outlined the proposed plan of treatment, but often lacked evidence of discussion relevant to whether the treatment plan was expected to improve the patient's condition. Legislative standards for determination of best interest, such as the Health Care Consent Act in Ontario, Canada, may provide guidance for intensivists to optimally document the rationales for proposed treatment plans.
Evaluation of an open access echocardiography service in the Netherlands: a mixed methods study of indications, outcomes, patient management and trends
Authors: van Heur Leanne MSG , Baur Leo HB , Tent Marleen , Lodewijks-van der Bolt Cara LB , Streppel Marjolijn , Winkens Ron AG , Stoffers Henri EJH
Published: February 2010

Background

In our region (Eastern South Limburg, The Netherlands) an open access echocardiography service started in 2002. It was the first service of this kind in The Netherlands. Our study aims were: (1) to evaluate demand for the service, participation, indications, echocardiography outcomes, and management by the general practitioner (GP); (2) to analyse changes in indications and outcomes over the years.

Methods

(1) Data from GP request forms, echocardiography reports and a retrospective GP questionnaire on management (response rate 83%) of 625 consecutive patients (Dec. 2002 - March 2007) were analysed cross-sectionally. (2) For the analysis of changes over the years, data from GP request forms and echocardiography reports of the first and last 250 patients that visited the service between Dec. 2002 and Feb. 2008 (n = 1001) were compared.

Results

The echocardiography service was used by 81% of the regional GPs. On average, a GP referred one patient per year to the service. Intended indications for the service were dyspnoea (32%), cardiac murmur (59%), and peripheral oedema (17%). Of the other indications (22%), one-third was for evaluation of suspected left ventricular hypertrophy (LVH). Expected outcomes were left ventricular dysfunction (LVD) (43%, predominantly diastolic) and valve disease (25%). We also found a high proportion of LVH (50%). Only 24% of all echocardiograms showed no relevant disease. The GP followed the cardiologist's advice to refer the patient for further evaluation in 71%. In recent patients, more echocardiography requests were done for 'cardiac murmur' and 'other' indications, but less for 'dyspnoea'. The proportions of patients with LVD, LVH and valve disease decreased and the proportion of patients with no relevant disease increased. The number of advices by the cardiologists increased.

Conclusion

Overall, GPs used the open access echocardiography service efficiently (i.e. with a high chance of finding relevant pathology), but efficiency decreased slightly over the years. To meet the needs of the GPs, indications might be widened with 'suspicion LVH'. Further specification of the indications for open access echocardiography - by defining a stepwise diagnostic approach including ECG and (NT-pro)BNP - might improve the service.
Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression
Authors: Lam Wilbur A , Cao Lizhi , Umesh Vaibhavi , Keung Albert J , Sen Shamik , Kumar Sanjay
Published: February 2010

Neuroblastoma is a pediatric malignancy characterized by tremendous clinical heterogeneity, in which some tumors are extremely aggressive while others spontaneously differentiate into benign forms. Because the degree of differentiation correlates with prognosis, and because differentiating agents such as retinoic acid (RA) have proven to decrease mortality, much effort has been devoted to identifying critical regulators of neuroblastoma differentiation in the cellular microenvironment, including cues encoded in the extracellular matrix (ECM). While signaling between tumor cells and the ECM is classically regarded to be based purely on biochemical recognition of ECM ligands by specific cellular receptors, a number of recent studies have made it increasingly clear that the biophysical properties of the ECM may also play an important role in this cross-talk. Given that RA-mediated neuroblastoma differentiation is accompanied by profound changes in cell morphology and neurite extension, both of which presumably rely upon mechanotransductive signaling systems, it occurred to us that mechanical cues from the ECM might also influence RA-mediated differentiation, which in turn might regulate clinically-relevant aspects of neuroblastoma biology. In this study, we tested this hypothesis by subjecting a series of neuroblastoma culture models to ECM microenvironments of varying mechanical stiffness and examined the regulatory role of ECM stiffness in proliferation, differentiation, and expression of tumor markers. We find that increasing ECM stiffness enhances neuritogenesis and suppresses cell proliferation. Remarkably, increasing ECM stiffness also reduces expression of N-Myc, a transcription factor involved in multiple aspects of oncogenic proliferation that is used for evaluating prognosis and clinical grading of neuroblastoma. Furthermore, the addition of RA enhances all of these effects for all ECM stiffnesses tested. Together, our data strongly support the notion that the mechanical signals from the cellular microenvironment influence neuroblastoma differentiation and do so synergistically with RA. These observations support further investigation of the role of microenvironmental mechanical signals in neuroblastoma proliferation and differentiation and suggest that pharmacological agents that modulate the underlying mechanotransductive signaling pathways may have a role in neuroblastoma therapy.
Age-dependent role of steroids in the regulation of growth of the hen follicular wall
Authors: Lebedeva Irina Y , Lebedev Vladimir A , Grossmann Roland , Parvizi Nahid
Published: February 2010

Background

The ovaries are the primary targets of senescence effects in mammalian and avian species. In the present study, relationships between reproductive aging, sex steroids and the growth pattern of the pre-ovulatory follicle wall were investigated using young hens with long clutch (YLC), old hens with long clutch (OLC), old hens with short clutch (OSC), and old hens with interrupted long clutch (OILC).

Methods

Experiment 1: Hens were sacrificed 1.5 and 14.5 h after ovulation. Experiment 2: YLC and OILC hens were sacrificed 3.5 h after treatments with LH and/or aminoglutethimide (AG), an inhibitor of steroid synthesis. Volumes of pre-ovulatory follicles (F1-F5) and plasma concentrations of ovarian steroids were determined. Experiment 3: Granulosa and theca cells from F3 follicles of OSC and/or YLC hens were exposed in vitro to estradiol-17beta (E2), testosterone (T) and LH and the proliferative activity of the cells was examined using CellTiter 96 Aqueous One Solution Assay.

Results

In YLC and OLC groups, the total volume of F1-F5 follicles rose between 1.5 and 14.5 h after ovulation (P < 0.01), negatively correlating with the plasma level of E2 (P < 0.01). There was no growth of pre-ovulatory follicles in the middle of the ovulatory cycle in the OSC group, with a positive correlation being present between E2 and the follicular volume (P < 0.05). In young hens, AG caused a rise in the total follicular volume. This rise was associated with a fall in E2 (r = -0.54, P < 0.05). E2 enhanced proliferation of granulosa cells from YLC and OSC groups. The proliferative activity of granulosa and theca cells of YLC hens depended on the interaction between T and LH (P < 0.01).

Conclusions

These data indicate for the first time that the growth pattern of pre-ovulatory follicles during the ovulatory cycle changes in the course of reproductive aging. E2 seems to play a dual role in this adjustment; it stimulates the growth of the follicular wall in reproductive aged hens, whereas it may inhibit this process in young birds. T and LH are apparently involved in the growth regulation during the pre-ovulatory surge in young hens.
Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome
Authors: Groom Harriet CT , Boucherit Virginie C , Makinson Kerry , Randal Edward , Baptista Sarah , Hagan Suzanne , Gow John W , Mattes Frank M , Breuer Judith , Kerr Jonathan R , Stoye Jonathan P , Bishop Kate N
Published: February 2010

Background

Detection of a retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), has recently been reported in 67% of patients with chronic fatigue syndrome. We have studied a total of 170 samples from chronic fatigue syndrome patients from two UK cohorts and 395 controls for evidence of XMRV infection by looking either for the presence of viral nucleic acids using quantitative PCR (limit of detection <16 viral copies) or for the presence of serological responses using a virus neutralisation assay.

Results

We have not identified XMRV DNA in any samples by PCR (0/299). Some serum samples showed XMRV neutralising activity (26/565) but only one of these positive sera came from a CFS patient. Most of the positive sera were also able to neutralise MLV particles pseudotyped with envelope proteins from other viruses, including vesicular stomatitis virus, indicating significant cross-reactivity in serological responses. Four positive samples were specific for XMRV.

Conclusions

No association between XMRV infection and CFS was observed in the samples tested, either by PCR or serological methodologies. The non-specific neutralisation observed in multiple serum samples suggests that it is unlikely that these responses were elicited by XMRV and highlights the danger of over-estimating XMRV frequency based on serological assays. In spite of this, we believe that the detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in at least four human serum samples indicates that XMRV infection may occur in the general population, although with currently uncertain outcomes.
sCD4-17b bifunctional protein: Extremely broad and potent neutralization of HIV-1 Env pseudotyped viruses from genetically diverse primary isolates
Authors: Lagenaur Laurel A , Villarroel Vadim A , Bundoc Virgilio , Dey Barna , Berger Edward A
Published: February 2010

Background

We previously described a potent recombinant HIV-1 neutralizing protein, sCD4-17b, composed of soluble CD4 attached via a flexible polypeptide linker to an SCFv of the 17b human monoclonal antibody directed against the highly conserved CD4-induced bridging sheet of gp120 involved in coreceptor binding. The sCD4 moiety of the bifunctional protein binds to gp120 on free virions, thereby enabling the 17b SCFv moiety to bind and block the gp120/coreceptor interaction required for entry. The previous studies using the MAGI-CCR5 assay system indicated that sCD4-17b (in concentrated cell culture medium, or partially purified) potently neutralized several genetically diverse HIIV-1 primary isolates; however, at the concentrations tested it was ineffective against several other strains despite the conservation of binding sites for both CD4 and 17b. To address this puzzle, we designed variants of sCD4-17b with different linker lengths, and tested the neutralizing activities of the immunoaffinity purified proteins over a broader concentration range against a large number of genetically diverse HIV-1 primary isolates, using the TZM-bl Env pseudotype assay system. We also examined the sCD4-17b sensitivities of isogenic viruses generated from different producer cell types.

Results

We observed that immunoaffinity purified sCD4-17b effectively neutralized HIV-1 pseudotypes, including those from HIV-1 isolates previously found to be relatively insensitive in the MAGI-CCR5 assay. The potencies were equivalent for the original construct and a variant with a longer linker, as observed with both pseudotype particles and infectious virions; by contrast, a construct with a linker too short to enable simultaneous binding of the sCD4 and 17b SCFv moieties was much less effective. sCD4-17b displayed potent neutralizing activity against 100% of nearly 4 dozen HIV-1 primary isolates from diverse genetic subtypes (clades A, B, C, D, F, and circulating recombinant forms AE and AG). The neutralization breadth and potency were superior to what have been reported for the broadly neutralizing monoclonal antibodies IgG b12, 2G12, 2F5, and 4E10. The activity of sCD4-17b was found to be similar against isogenic virus particles from infectious molecular clones derived either directly from the transfected producer cell line or after a single passage through PBMCs; this contrasted with the monoclonal antibodies, which were less potent against the PMBC-passaged viruses.

Conclusions

The results highlight the extremely potent and broad neutralizing activity of sCD4-17b against genetically diverse HIV-1 primary isolates. The bifunctional protein has potential applications for antiviral approaches to combat HIV infection.
New method of measuring wrist joint position sense avoiding cutaneous and visual inputs
Authors: Gay Andre , Harbst Kimberly , Kaufman Kenton R , Hansen Diana K , Laskowski Edward R , Berger Richard A
Published: February 2010

Background

Aspects of afferent inputs, generally termed proprioception, are being increasingly studied. Extraneous factors such as cutaneous inputs can dramatically interfere while trying to design studies in order to determine the participation of the different structures involved in proprioception in the wrist position sense. We tried to determine validity and repeatability of a new wrist joint position measurement device using methodology designed to minimize extraneous factors and isolate muscle and joint inputs.

Methods

In order to test the reliability of the system, eighty young-adult subjects without musculoskeletal or neurologic impairments affecting the right upper extremity were tested using a custom made motion tracking system. Testing consisted of two conditions: active reproduction of active placement and passive reproduction of passive placement. Subjects performed two repetitions of each target position (10, 20, and 30° of flexion and extension) presented in a random order. Test- retest reliability was then tested.

Results

The average constant error in the passive condition was -0.7° ± 4.7° as compared to the active condition at 3.7° ± 5.1°. Average absolute error in the passive condition was 4.9° ± 2.9° compared to the active condition in which absolute error was 5.9° ± 3.5°.

Discussion

Test-retest repeatability in both conditions was less than the 5° magnitude typical of clinical goniometry. Errors in the active condition (less than 2°) were slightly smaller than the passive condition, and the passive condition was also associated with poorer consistency between apparatus sensors and skin sensors.

Conclusions

The current system for measurement of wrist joint proprioception allows the researcher to decrease extraneous influences that may affect joint position sense awareness, and will help in future study aiming to determine precisely the role of the different structure involved in proprioception.
Baculovirus immediately early 1, a mediator for homologous regions enhancer function in trans
Authors: Lin Xu'ai , Chen Yin , Yi Yongzhu , Zhang Zhifang
Published: February 2010

Background

Enhancers are DNA sequences that serve as binding sites for regulatory proteins, and stimulate transcriptional activity independent of their positions and orientations with respect to the transcriptional initiation site. Previous studies considered that baculovirus homologous regions (hrs) function as enhancers in cis. In our study, a plasmid containing homologous region 3 (hr3) enhancer from Bombyx mori nucleopolyhedrovirus (BmNPV) failed to enhance transcription of promoter in other plasmid in co-transfection assays, but strong stimulation occurred when cells were infected by BmNPV.

Results

The cotransfection results of each BmNPV genomic library plasmid, hr3 plasmid and reporter plasmid showed that there were eight library plasmids stimulated the luciferase gene expression remarkably. Sequencing these plasmids revealed that each of them contained the ie-1 gene. Transfected plasmids, containing ie-1, hr3 and various origin promoter drove reporter gene showed the function was even retained. Cotransfection of hr3 functional dissected fragment and ie-1 revealed that the 30-bp imperfect palindrome destroyed fragment can't enhance reporter gene expression even though transfected with ie-1.

Conclusion

IE-1 was the only early factor of BmNPV that could act as a mediator for hr enhancer function in trans and the trans-function was achieved with a broad-spectrum of promoters. The 30-bp imperfect palindrome was the elementary molecular structure by which IE-1 participated in the enhancer function in trans.
Elevated CSF outflow resistance associated with impaired lymphatic CSF absorption in a rat model of kaolin-induced communicating hydrocephalus
Authors: Nagra Gurjit , Wagshul Mark E , Rashid Shams , Li Jie , McAllister J Pat , Johnston Miles
Published: February 2010

Background

We recently reported a lymphatic cerebrospinal fluid (CSF) absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance).

Methods

Kaolin was injected into the basal cisterns of Sprague Dawley rats. The development of hydrocephalus was assessed using magnetic resonance imaging (MRI). In one group of animals at about 3 weeks after injection, the movement of intraventricularly injected iodinated human serum albumin (125I-HSA) into the olfactory turbinates provided an estimate of CSF transport through the cribriform plate into nasal lymphatics (n = 18). Control animals received saline in place of kaolin (n = 10). In a second group at about 3.5 weeks after kaolin injection, intraventricular pressure was measured continuously during infusion of saline into the spinal subarachnoid space at various flow rates (n = 9). CSF outflow resistance was calculated as the slope of the steady-state pressure versus flow rate. Control animals for this group either received no injections (intact: n = 11) or received saline in place of kaolin (n = 8).

Results

Compared to saline injected controls, lateral ventricular volume in the kaolin group was significantly greater (0.087 ± 0.013 ml, n = 27 versus 0.015 ± 0.001 ml, n = 17) and lymphatic function was significantly less (2.14 ± 0.72% injected/g, n = 18 versus 6.38 ± 0.60% injected/g, n = 10). Additionally, the CSF outflow resistance was significantly greater in the kaolin group (0.46 ± 0.04 cm H2O.μL-1.min, n = 9) than in saline injected (0.28 ± 0.03 cm H2O.μL-1.min, n = 8) or intact animals (0.18 ± 0.03 cm H2O.μL-1.min, n = 11). There was a significant positive correlation between CSF outflow resistance and ventricular volume.

Conclusions

The data suggest that the impediment to lymphatic CSF absorption in a kaolin-induced model of communicating hydrocephalus has a significant impact on global CSF absorption. A lymphatic CSF absorption deficit would appear to play some role (either direct or indirect) in the pathogenesis of ventriculomegaly.
Poorer sustained attention in bipolar I than bipolar II disorder
Authors: Kung Chian-Huei , Lee Sheng-Yu , Chang Yun-Hsuan , Wu Jo Yung-Wei , Chen Shiou-Lan , Chen Shih-Heng , Chu Chun-Hsien , Lee I-Hui , Yeh Tzung-Lieh , Yang Yen-Kuang , Lu Ru-Band
Published: February 2010

Background

Nearly all information processing during cognitive processing takes place during periods of sustained attention. Sustained attention deficit is among the most commonly reported impairments in bipolar disorder (BP). The majority of previous studies have only focused on bipolar I disorder (BP I), owing to underdiagnosis or misdiagnosis of bipolar II disorder (BP II). With the refinement of the bipolar spectrum paradigm, the goal of this study was to compare the sustained attention of interepisode patients with BP I to those with BP II.

Methods

In all, 51 interepisode BP patients (22 with BP I and 29 with BP II) and 20 healthy controls participated in this study. The severity of psychiatric symptoms was assessed by the 17-item Hamilton Depression Rating Scale and the Young Mania Rating Scale. All participants undertook Conners' Continuous Performance Test II (CPT-II) to evaluate sustained attention.

Results

After controlling for the severity of symptoms, age and years of education, BP I patients had a significantly longer reaction times (F(2,68) = 7.648, P = 0.001), worse detectability (d') values (F(2,68) = 6.313, P = 0.003) and more commission errors (F(2,68) = 6.182, P = 0.004) than BP II patients and healthy controls. BP II patients and controls scored significantly higher than BP I patients for d' (F = 6.313, P = 0.003). No significant difference was found among the three groups in omission errors and no significant correlations were observed between CPT-II performance and clinical characteristics in the three groups.

Conclusions

These findings suggested that impairments in sustained attention might be more representative of BP I than BP II after controlling for the severity of symptoms, age, years of education and reaction time on the attentional test. A longitudinal follow-up study design with a larger sample size might be needed to provide more information on chronological sustained attention deficit in BP patients, and to illustrate clearer differentiations between the three groups.
Occupational health legislation and practices related to seafarers on passenger ships focused on communicable diseases: results from a European cross-sectional study (EU SHIPSAN PROJECT)
Authors: Rachiotis George , Mouchtouri Varvara A , Schlaich Clara , Riemer Tobias , Martinez Carmen Varela , Nichols Gordon , Bartlett Christopher LR , Kremastinou Jenny , Hadjichristodoulou Christos ,   the SHIPSAN partnership**
Published: February 2010

Background

Seafarers play an important role in the transmission of communicable diseases. The aim of the present study is to draw information and identify possible gaps on occupational health practices related to seafarers sailing on ships within the European Union Member States (EU MS) with focus on communicable diseases.

Methods

A structured questionnaire was sent to competent authorities from 21 EU MS. The questionnaire included questions about occupational health policies, medical certification of seafarers, communicable diseases reporting and relevant legislation. Descriptive analysis of the data was conducted by the use of Epi Info software: EU MS were categorized in four priority groups (A, B, C, D) based on: number of passenger ships visits, volume of passengers, and number of ports in each country. Moreover, EU MS were categorized to old and new, based on the date of entry in the EU.

Results

All 21 countries with relevant competent authorities responded to the questionnaire. The existence of specific national legislation/regulation/guidelines related to vaccination of seafarers was reported by three out of the 21 (14%) responding authorities. Surveillance data of communicable diseases related to seafarers are collected and analyzed by 4 (19%) authorities. Five out of 21 of the responding countries (24%) reported that tuberculin test result is required for the issuance of seafarer's medical certificate while a great variety of medical examination is required for the issuance of this certificate among countries.

Gaps on occupational health services focused on communicable diseases related to maritime occupation have been reported by 33% of the responding countries.

Responding authorities from Group A and B had the highest percentage of reported gaps followed by groups C and D. Old MS reported a higher frequency regarding gaps on occupational health services in comparison to new MS.

Conclusion

Our results revealed heterogeneity regarding occupational health of maritime employees in EU MS. This work provides some evidence that further work at international and European level could be considered, in order to explore the potential for harmonized initiatives regarding occupational health of seafarers.
Recurrent vitreous occlusion of glaucoma drainage device tube in a patient with glaucoma in aphakia: a case report
Authors: Ang Ghee Soon , Goh Yi Wei , Azuara-Blanco Augusto
Published: February 2010

Patients with spontaneous lens dislocation and glaucoma can be challenging to manage. We present a forty-six year old Caucasian lady who was referred with bilateral high intraocular pressure, and was subsequently diagnosed with glaucoma in association with lens dislocation and Marfan syndrome. Baerveldt glaucoma drainage device tubes were inserted in both eyes due to poor response to medical therapy. However, this was complicated by recurrent vitreous occlusion of both glaucoma drainage tubes requiring further multiple surgical interventions. There have not been any further recurrences of vitreous incarceration or posterior segment complications since, but the patient remains under close follow-up.
Survival and self-renewing capacity of breast cancer initiating cells during fractionated radiation treatment
Authors: Lagadec Chann , Vlashi Erina , Della Donna Lorenza , Meng YongHong , Dekmezian Carmen , Kim Kwanghee , Pajonk Frank
Published: February 2010

Introduction

Recent data indicate a hierarchical organization of many solid cancers, including breast cancer, with a small number of cancer initiating cells (CICs) that have the ability to self-renew and exhibit multi-lineage potency. We, and others, have demonstrated that CICs in breast cancer and glioma are relatively resistant to ionizing radiation if compared to their non-tumorigenic counterparts. However, the extent of the remaining self-renewing capacity of CICs after fractions of radiation is currently unknown. We hypothesized that CICs, in contrast to their non-tumorigenic counterparts, not only survive fractions of ionizing radiation but also retain the CIC phenotype as defined by operational means.

Methods

We used two marker systems to identify breast CICs (CD24-/low/CD44high, or lack of proteasome activity) and performed sphere-forming assays after multiple clinical fractions of radiation. Lineage tracking was performed by membrane staining. Cell cycle distribution and RNA content were assessed by flow cytometry and senescence was assessed via β-galactosidase staining.

Results

We demonstrated that irradiated CICs survived and retained their self-renewal capacity for at least four generations. We show that fractionated radiation not only spared CICs but also mobilized them from a quiescent/G0 phase of the cell cycle into actively cycling cells, while the surviving non-tumorigenic cells were driven into senescence.

Conclusions

The breast CIC population retains increased self-renewal capacity over several generations and therefore, we conclude that increases in the number of CICs after sublethal doses of radiation have potential clinical importance. Prevention of this process may lead to improved clinical outcome.
Genome-wide analysis of the diatom cell cycle unveils a novel type of cyclins involved in environmental signaling
Authors: Huysman Marie JJ , Martens Cindy , Vandepoele Klaas , Gillard Jeroen , Rayko Edda , Heijde Marc , Bowler Chris , Inzé Dirk , Peer Yves Van de , De Veylder Lieven , Vyverman Wim
Published: February 2010

Background

Despite the enormous importance of diatoms in aquatic ecosystems and their broad industrial potential, little is known about their life cycle control. Diatoms typically inhabit rapidly changing and unstable environments, suggesting that cell cycle regulation in diatoms must have evolved to adequately integrate various environmental signals. The recent genome sequencing of Thalassiosira pseudonana and Phaeodactylum tricornutum allows us to explore the molecular conservation of cell cycle regulation in diatoms.

Results

By profile-based annotation of cell cycle genes, counterparts of conserved as well as new regulators were identified in T. pseudonana and P. tricornutum. In particular, the cyclin gene family was found to be expanded extensively compared to that of other eukaryotes and a novel type of cyclins was discovered, the diatom-specific cyclins. We established a synchronization method for P. tricornutum that enabled assignment of the different annotated genes to specific cell cycle phase transitions. The diatom-specific cyclins are predominantly expressed at the G1-to-S transition and some respond to phosphate availability, hinting at a role in connecting cell division to environmental stimuli.

Conclusion

The discovery of highly conserved and new cell cycle regulators suggests the evolution of unique control mechanisms for diatom cell division, probably contributing to their ability to adapt and survive under highly fluctuating environmental conditions.
HIV-1 Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral production from latency
Authors: Hoshino Shigeki , Konishi Mitsuru , Mori Masako , Shimura Mari , Nishitani Chiaki , Kuroki Yoshio , Koyanagi Yoshio , Kano Shigeyuki , Itabe Hiroyuki , Ishizaka Yukihito
Published: February 2010

A TLR4/MyD88 pathway was activated via oxidized phosphatidylcholine caused by Vpr of HIV-1.

Vpr, a HIV-1 accessory protein, was believed to be present in the plasma of HIV-1-positive patients, and our previous work demonstrated the presence of plasma Vpr in 20 out of 52 patients. Interestingly, our data revealed that patients’ viral titer was correlated with the level of Vpr detected in their plasma. Here, we first show that rVpr, when incubated with human monocytes or MDMs, caused viral production from latently infected cells, and IL-6 was identified as a responsible factor. The induction of IL-6 by rVpr was dependent on signaling through TLR4 and its adaptor molecule, MyD88. We next provide evidence that rVpr induced the formation of OxPC and that a mAb against OxPC blocked rVpr-induced IL-6 production with the concomitant attenuation of MAPK activation. Moreover, the addition of NAC, a scavenger of ROS, abrogated the rVpr-induced formation of OxPC, the phosphorylation of C/EBP-β, a substrate of MAPK, and IL-6 production. As rIL-6 reactivated viral replication in latently infected cells, our data indicate that rVpr-induced oxidative stress triggers cell-based innate immune responses and reactivates viral production in latently infected cells via IL-6 production. Our results suggest that Vpr should be monitored based on the viral titer, and they provide the rationale for the development of novel, anti-AIDS therapeutics targeting Vpr.
Plasmacytoid dendritic cells in HIV infection: striking a delicate balance
Authors: Fitzgerald-Bocarsly Patricia , Jacobs Evan S
Published: February 2010

Review of the plasmacytoid dendritic cells and their potential for beneficial or detrimental roles in HIV-1 infection.

pDC are the most potent IFN-α-producing cells in the body and serve as a vital link between innate and adaptive immunity. Deficiencies in pDC function were among the earliest observations of immune dysfunction in HIV-1 infection. Herein, we review the status of pDC in individuals with HIV-1 infection and the potential role of these cells in pathogenesis. We begin by reviewing the basic properties of pDC and then discuss the compromise in circulating pDC numbers and function in early and viremic HIV-1 infection and mechanisms that might account for their depletion in HIV-infected patients. In addition, we review the evidence that chronic production of IFN-α, probably through the chronic activation of pDC, is central to the immune activation that is so detrimental in HIV infection. Finally, we discuss the importance of balance in pDC numbers and function and the potential value of using absolute pDC counts and function as a biomarker, along with CD4+ cell counts and VL in HIV-1-infected patients.
Ragnar Frisch's Conception of Econometrics
Authors: Bjerkholt Olav , Dupont Ariane
Published: February 2010

Ragnar Frisch is well known for his contribution to econometrics as a new discipline in the 1930s and for his role in founding of the Econometric Society and as editor of Econometrica. Despite his active role within the econometrics community, it may be argued that his overall conception of econometrics is insufficiently conveyed in the history of economics literature. This essay aims at illuminating key features of Frisch's scientific conception, drawing partly on unpublished works unearthed from his archives. Among these are a series of eight lectures on the theory and methods of econometrics given by Frisch at the Poincaré Institute at the University of Paris in 1933, as well as extensive lecture notes from Yale University in 1930.

These largely unknown documents elaborate on Frisch's scientific views, how he aimed at modeling economics on physics by transferring methodological principles, and on the methods he proposed for economics, such as his axiomatization approach, his structural modeling approach, which became a cornerstone for macroeconomics, his refined explication of concepts such as static/dynamic, micro/macro, and equilibrium, and his concern with the probabilistic nature of the real economic world. One can discern in these documents also that an essential part of Frisch's concept of econometrics as a science was its instrumental role in policy preparation for welfare and improvement of human conditions.
The Econometricians' Statisticians, 1895–1945
Authors: Aldrich John
Published: February 2010

Histories of econometrics describe what econometricians did with the ideas of statisticians—correlation, regression, maximum likelihood, testing statistical hypotheses, etc. The transfer of these ideas was made possible by institutions, practices, and personal contacts between statisticians and econometricians. This essay complements the usual history of econometrics with an account of these transactions from the statisticians' side. I concentrate on four statisticians and their interactions with econometricians: Karl Pearson, whose influence was exercised in the years before the First World War; Ronald Fisher, who began to be influential in the late 1920s; Jerzy Neyman, who appeared in the late 1930s; and Abraham Wald in the early 1940s.
Defining Obscenity, Inventing Pornography: The Limits of Censorship in Rétif de La Bretonne
Authors: Wyngaard Amy S.
Published: February 2010

Most critical accounts of the history of pornography note that the term is traceable to Nicolas-Edme Rétif de la Bretonne's Pornographe, which they dismiss in the same breath because of its nonpornographic status. Although Rétif wrote only one pornographic novel, L'Anti-Justine (1798), his contributions to the genre merit further analysis. This essay argues that Rétif played an important role in circumscribing the moral and legal limits of sexual representation in the eighteenth century and beyond. He did so not by producing blatantly obscene texts but by working to push the boundaries of decency and propriety while inviting censors and the public to hone their understanding of these concepts. In producing increasingly daring versions of Le paysan perverti (1775), Rétif repeatedly forced authorities to redraw the line between the passable and the prohibited. In this way he helped shape the category of the illicit at its borders, contributing more to the development of pornography than simply its name.
“Very Saleable Articles, Indeed”: Margaret Oliphant's Repackaging of Sensational Finance
Authors: Wagner Tamara S.
Published: February 2010

Examining the impact of mid-Victorian sensationalism on the shaping of the nineteenth-century novel, this essay calls renewed attention to the intricacies of genre formation. Taking as its point of departure the notorious “sensational sixties,” it tracks the increasingly self-reflexive adaptations of the sensation genre's most popular paradigms in the following decades. Oliphant's At His Gates (1872) capitalized on the quickly established alignment between finance and sensation not so much to condemn commercial pressures as to turn them to good effect as the shapers of new literary motifs. Featuring a moderately successful painter who produces his one truly outstanding piece, ironically, when driven to despair by a financial swindle, At His Gates was not merely Oliphant's most fully realized fictional engagement with sensational narratives of Victorian economic crises. Reflecting its author's own dilemma in the struggles of a speculating painter, the novel addressed and exploited key intertextual exchanges at the Victorian book market.
Medical Licensing Board Characteristics and Physician Discipline: An Empirical Analysis
Authors: Law Marc T. , Hansen Zeynep K.
Published: February 2010

This article investigates the relationship between the characteristics of medical licensing boards and the frequency with which boards discipline physicians. Specifically, we take advantage of variation in the structure of medical licensing boards between 1993 and 2003 to determine the effect of organizational and budgetary independence, public oversight, and resource constraints on rates of physician discipline. We find that larger licensing boards, boards with more staff, and boards that are organizationally independent from state government discipline doctors more frequently. Public oversight and political control over board budgets do not appear to influence the extent to which medical licensing boards discipline doctors. These findings are broadly consistent with theories of regulatory behavior that emphasize the importance of bureaucratic autonomy for effective regulatory enforcement.
Role of TI-VAMP and CD82 in EGFR cell-surface dynamics and signaling
Authors: Danglot Lydia , Chaineau Mathilde , Dahan Maxime , Gendron Marie-Claude , Boggetto Nicole , Perez Franck , Galli Thierry
Published: February 2010

The v-SNARE TI-VAMP (VAMP7) mediates exocytosis during neuritogenesis, phagocytosis and lysosomal secretion. It localizes to endosomes and lysosomes but also to the trans-Golgi network. Here we show that depletion of TI-VAMP enhances the endocytosis of activated EGF receptor (EGFR) without affecting constitutive endocytosis of EGFR, or transferrin uptake. This increased EGFR internalization is mainly clathrin dependent. Searching for defects in EGFR regulators, we found that TI-VAMP depletion reduces the cell surface amount of CD82, a tetraspanin known to control EGFR localization in microdomains. We further show that TI-VAMP is required for secretion from the Golgi apparatus to the cell surface, and that TI-VAMP-positive vesicles transport CD82. Quantum dots video-microscopy indicates that depletion of TI-VAMP, or its cargo CD82, restrains EGFR diffusion and the area explored by EGFR at the cell surface. Both depletions also impair MAPK signaling and enhance endocytosis of activated EGFR by increased recruitment of AP-2. These results highlight the role of TI-VAMP in the secretory pathway of a tetraspanin, and support a model in which CD82 allows EGFR entry in microdomains that control its clathrin-dependent endocytosis and signaling.
Availability analysis of railway track circuits
Authors: Patra A P , Kumar U
Published: February 2010

Railways are expected to operate with ever increasing availability. The availability of railway systems and subsystems influences the overall operational availability. As the track circuit is a key component of railway signalling and control, it can contribute significantly to the loss of availability of the railway system. One way to increase the availability of the track circuit is by implementing a proper maintenance policy. In this article, Petri-nets have been used to develop models for availability analysis of the track circuit for both time-based and condition-based maintenance. A sensitivity analysis has been performed to estimate the effect of maintenance parameters on availability performance using cost—benefit analysis.