bluuebunny/crossref_metadata_2025 huggingface dataset:
OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background
Authors: Pierron Denis , Ferré Marc , Rocher Christophe , Chevrollier Arnaud , Murail Pascal , Thoraval Didier , Amati-Bonneau Patrizia , Reynier Pascal , Letellier Thierry
Published: July 2009

Background

Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the most frequent forms of hereditary optic neuropathies. LHON is associated with mitochondrial DNA (mtDNA) mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mitochondrial protein involved in the mitochondrial inner membrane remodeling. A striking influence of mtDNA haplogroup J on LHON expression has been demonstrated and it has been recently suggested that this haplogroup could also influence ADOA expression. In this study, we have tested the influence of mtDNA backgrounds on OPA1 mutations.

Methods

To define the relationships between OPA1 mutations and mtDNA backgrounds, we determined the haplogroup affiliation of 41 French patients affected by OPA1-related ADOA by control-region sequencing and RFLP survey of their mtDNAs.

Results

The comparison between patient and reference populations did not revealed any significant difference.

Conclusion

Our results argue against a strong influence of mtDNA background on ADOA expression. These data allow to conclude that OPA1 could be considered as a "severe mutation", directly responsible of the optic atrophy, whereas OPA1-negative ADOA and LHON mutations need an external factor(s) to express the pathology (i.e. synergistic interaction with mitochondrial background).
Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment
Authors: Schnakers Caroline , Vanhaudenhuyse Audrey , Giacino Joseph , Ventura Manfredi , Boly Melanie , Majerus Steve , Moonen Gustave , Laureys Steven
Published: July 2009

Background

Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R).

Methods

We prospectively followed 103 patients (55 ± 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.'

Results

Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings.

Conclusion

Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus.
A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivoglioblastoma models
Authors: Boumendjel Ahcene , McLeer-Florin Anne , Champelovier Pierre , Allegro Diane , Muhammad Dima , Souard Florence , Derouazi Madiha , Peyrot Vincent , Toussaint Bertrand , Boutonnat Jean
Published: July 2009

Background

Over the past decades, in spite of intensive search, no significant increase in the survival of patients with glioblastoma has been obtained. The role of the blood-brain barrier (BBB) and especially the activity of efflux pumps belonging to the ATP Binding Cassette (ABC) family may, in part, explain this defect.

Methods

Thein-vitroactivities of JAI-51 on cell proliferation were assessed by various experimental approaches in four human and a murine glioblastoma cell lines. Using drug exclusion assays and flow-cytometry, potential inhibitory effects of JAI-51 on P-gp and BCRP were evaluated in sensitive or resistant cell lines. JAI-51 activity onin-vitromicrotubule polymerization was assessed by tubulin polymerization assay and direct binding measurements by analytical ultracentrifugation. Finally, a model of C57BL/6 mice bearing subcutaneous GL26 glioblastoma xenografts was used to assess the activity of the title compoundin vivo. An HPLC method was designed to detect JAI-51 in the brain and other target organs of the treated animals, as well as in the tumours.

Results

In the four human and the murine glioblastoma cell lines tested, 10 μM JAI-51 inhibited proliferation and blocked cells in the M phase of the cell cycle, via its activity as a microtubule depolymerising agent. This ligand binds to tubulin with an association constant of 2 × 105M-1, overlapping the colchicine binding site. JAI-51 also inhibited the activity of P-gp and BCRP, without being a substrate of these efflux pumps. Thesein vitrostudies were reinforced by ourin vivoinvestigations of C57BL/6 mice bearing GL26 glioblastoma xenografts, in which JAI-51 induced a delay in tumour onset and a tumour growth inhibition, following intraperitoneal administration of 96 mg/kg once a week. In accordance with these results, JAI-51 was detected by HPLC in the tumours of the treated animals. Moreover, JAI-51 was detected in the brain, showing that the molecule is also able to cross the BBB.

Conclusion

Thesein vitroandin vivodata suggest that JAI-51 could be a good candidate for a new treatment of tumours of the CNS. Further investigations are in progress to associate the title compound chemotherapy to radiotherapy in a rat model.
Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer
Authors: Li Jianghong , Sherman-Baust Cheryl A , Tsai-Turton Miyun , Bristow Robert E , Roden Richard B , Morin Patrice J
Published: July 2009

Background

The absence of highly sensitive and specific serum biomarkers makes mass screening for ovarian cancer impossible. The claudin proteins are frequently overexpressed in ovarian cancers, but their potential as prognostic, diagnostic, or detection markers remains unclear. Here, we have explored the possible use of these proteins as screening biomarkers for ovarian cancer detection.

Methods

Claudin protein shedding from cells was examined by immunoblotting of conditioned culture media. The presence of claudins in exosomes released from ovarian cancer cells was demonstrated by sucrose gradient separation and immunogold electron microscopy experiments. Claudin-4-containing exosomes in the plasma of ovarian cancer patients were evaluated in a pilot panel of 63 ovarian cancer patients and 50 healthy volunteers. The CA125 marker was also assessed in these samples and compared with claudin-4 positivity.

Results

We show that full-length claudins can be shed from ovarian cancer cells in culture and found in the media as part of small lipid vesicles known as exosomes. Moreover, 32 of 63 plasma samples from ovarian cancer patients exhibited the presence of claudin-4-containing exosomes. In contrast, only one of 50 samples from individuals without cancer exhibited claudin-4-positive exosomes. In our small panel, at a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51% and 71%, respectively. The two tests did not appear to be independent and were strongly correlated.

Conclusion

Our work shows for the first time that claudin-4 can be released from ovarian cancer cells and can be detected in the peripheral circulation of ovarian cancer patients. The development of sensitive assays for the detection of claudin-4 in blood will be crucial in determining whether this approach can be useful, alone or in combination with other screening methods, for the detection of ovarian cancer.
Enhanced macrophage tropism of HIV in brain and lymphoid tissues is associated with sensitivity to the broadly neutralizing CD4 binding site antibody b12
Authors: Dunfee Rebecca L , Thomas Elaine R , Gabuzda Dana
Published: July 2009

Macrophages in the central nervous system (CNS) and other tissues are an important cellular reservoir for human immunodeficiency virus type 1 (HIV) infection, particularly in the later stages of disease. Macrophage-tropic HIV strains have an enhanced capacity to enter cells expressing low levels of CD4 through mechanisms that are not well understood. Here, we use a panel of primary HIV envelopes from brain and lymphoid tissues to examine the relationship between neutralization sensitivity to reagents targeting the CD4 binding site and virus entry into macrophages. Neutralization assays using pseudotyped viruses showed an association between the capacity of HIV to enter macrophages and increased sensitivity to the broadly neutralizing monoclonal antibody (mAb) b12, which recognizes a conserved epitope overlapping the CD4 binding site, but not sensitivity to soluble CD4 (sCD4) or b6, a non-neutralizing CD4 binding site mAb. Furthermore, loss of an N-linked glycosylation site at position 386 in the V4 region of Env enhanced macrophage tropism together with b12 sensitivity, but not neutralization by sCD4, b6, or a broadly neutralizing AIDS patient serum. These findings suggest that exposure of the b12 epitope, rather than exposure of the CD4 binding site per se, enhances HIV macrophage tropism, possibly by exposing a region on the outer domain of gp120 that is initially recognized by CD4. These findings suggest overlap between specific gp120 determinants in or near the b12 epitope and those conferring macrophage tropism.
High rate of unintended pregnancy among pregnant women in a maternity hospital in Córdoba, Argentina: a pilot study
Authors: Palena Celina , Bahamondes M Valeria , Schenk Verónica , Bahamondes Luis , Fernandez-Funes Julio
Published: July 2009

Background

Although Argentina has a new law on Reproductive Health, many barriers continue to exist regarding provision of contraceptive methods at public healthcare facilities.

Methods

We asked 212 pregnant women selected at random at the Maternity and Neonatal Hospital, Córdoba, Argentina, to participate in our descriptive study. Women were asked to complete a structured questionnaire. The objectives were to determine the rate of unintended pregnancies, reasons for not using contraception, past history of contraceptive use, and intended future use.

Results

Two hundred women responded to the questionnaire. Forty percent of the women stated that they had never used contraception and pregnancy was declared unintended by 65%. In the unintended pregnancy group, almost 50% of women said that they had not been using a contraceptive method because they were "unaware about contraception", and 25% stated that their contraceptive method had failed. Almost 85% of women stated that they intended to use contraception after delivery.

Conclusion

Approximately two-thirds of all pregnancies in this sample were unintended. Although the data is limited by the small sample size, our findings suggest that our government needs to invest in counseling and in improving the availability and access to contraceptive methods.
Higher activation of TLR9 in plasmacytoid dendritic cells by microbial DNA compared with self-DNA based on CpG-specific recognition of phosphodiester DNA
Authors: Coch Christoph , Busch Nicolas , Wimmenauer Vera , Hartmann Evelyn , Janke Markus , Abdel-Mottaleb Mona Mohamed Ahmed , Lamprecht Alf , Ludwig Janos , Barchet Winfried , Schlee Martin , Hartmann Gunther
Published: July 2009

Mammalian genomic DNA complexed to the natural antimicrobial cationic peptide LL37 induces type I interferon but less than bacterial DNA or CG-dinucleotide containing oligodeoxynucleotides.

TLR9 detects DNA in endolysosomal compartments of human B cells and PDC. Recently, the concept of the CpG motif specificity of TLR9-mediated detection, specifically of natural phosphodiester DNA, has been challenged. Unlike in human B cells, CpG specificity of natural phosphodiester DNA recognition in human PDC has not been analyzed in the literature. Here, we found that the induction of IFN-α and TNF-α in human PDC by phosphodiester ODNs containing one or two CG dinucleotides was reduced to a lower level when the CG dinucleotides were methylated and was abolished if the CGs were switched to GCs. Consistent with a high frequency of unmethylated CG dinucleotides, bacterial DNA induced high levels of IFN-α in PDC; IFN-α was reduced but not abolished upon methylation of bacterial DNA. Mammalian DNA containing low numbers of CG dinucleotides, which are frequently methylated, induced IFN-α in PDC consistently but on a much lower level than bacterial DNA. For activation of PDC, phosphodiester ODNs and genomic DNA strictly required complexation with cationic molecules such as the keratinocyte-derived antimicrobial peptide LL37 or a scrambled derivative. In conclusion, we demonstrate that self-DNA complexed to cationic molecules activate PDC and thus, indeed, may function as DAMPs; nevertheless, the preference of PDC for CpG containing DNA provides the basis for the discrimination of microbial from self-DNA even if DNA is presented in the condensed form of a complex.
Estrogen Receptor, Progesterone Receptor, Human Epidermal Growth Factor Receptor 2 (HER2), and Epidermal Growth Factor Receptor Expression and Benefit From Lapatinib in a Randomized Trial of Paclitaxel With Lapatinib or Placebo As First-Line Treatment in HER2-Negative or Unknown Metastatic Breast Cancer
Authors: Finn Richard S. , Press Michael F. , Dering Judy , Arbushites Michael , Koehler Maria , Oliva Cristina , Williams Lisa S. , Di Leo Angelo
Published: July 2009

Purpose

Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) with activity in HER2-amplified metastatic breast cancer (MBC). Its role in non–HER2-amplified MBC remains unclear. EGF30001, a phase III trial of lapatinib and paclitaxel versus paclitaxel and placebo, demonstrated lapatinib does not significantly benefit HER2-negative or HER2-unselected patients with MBC. Published data support interactions between steroid hormone and peptide growth factor signaling. We hypothesized that molecular subgroups may exist within EGF30001 that would benefit from lapatinib.

Methods

A blinded, retrospective biomarker evaluation was performed using immunohistochemistry to semiquantitate estrogen (ER), progesterone (PR), and EGFR expression. HER2 amplification was determined by fluorescent in situ hybridization. Effects of these biomarkers on event-free survival (EFS) were examined in patients with available tissue (n = 493).

Results

Lapatinib improved median EFS in HER2-amplified, ER- or PR-positive MBC (n = 36; 5.7 v 4.5 months; P = .351); benefit was greater and statistically significant in HER2-amplified, ER-negative, PR-negative MBC (n = 42; 8.3 v 5.0 months; P = .007). In HER2-negative, ER-positive MBC, median EFS improvement varied by degree of PR expression (H-score): no benefit if PR-strong (n = 133; 9.3 v 7.3 months; P = .373), benefit if PR-weak (n = 50; 7.3 v 2.4 months; P = .026), and potential antagonism if PR-negative (n = 40; 3.7 v 7.2 months; P = .004). No benefit was seen in triple-negative MBC (n = 131; median EFS, 4.6 v 4.8 months; P = .255). EGFR expression was not correlated with benefit from lapatinib.

Conclusion

Although subgroups are small, these analyses support the hypothesis that semiquantitative determination of hormone receptor status may be a surrogate for EGFR and/or HER2 dependency.
Absence of Progression As Assessed by Response Evaluation Criteria in Solid Tumors Predicts Survival in Advanced GI Stromal Tumors Treated With Imatinib Mesylate: The Intergroup EORTC-ISG-AGITG Phase III Trial
Authors: Le Cesne Axel , Van Glabbeke Martine , Verweij Jaap , Casali Paolo G. , Findlay Michael , Reichardt Peter , Issels Rolf , Judson Ian , Schoffski Patrick , Leyvraz Serge , Bui Binh , Hogendoorn Pancras C.W. , Sciot Raf , Blay Jean-Yves
Published: July 2009

Purpose

From February 2001 to February 2002, 946 patients with advanced GI stromal tumors (GISTs) treated with imatinib were included in a controlled EORTC/ISG/AGITG (European Organisation for Research and Treatment of Cancer/Italian Sarcoma Group/Australasian Gastro-Intestinal Trials Group) trial. This analysis investigates whether the response classification assessed by RECIST (Response Evaluation Criteria in Solid Tumors), predicts for time to progression (TTP) and overall survival (OS).

Patients and Methods

Per protocol, the first three disease assessments were done at 2, 4, and 6 months. For the purpose of the analysis (landmark method), disease response was subclassified in six categories: partial response (PR; > 30% size reduction), minor response (MR; 10% to 30% reduction), no change (NC) as either NC− (0% to 10% reduction) or NC+ (0% to 20% size increase), progressive disease (PD; > 20% increase/new lesions), and subjective PD (clinical progression).

Results

A total of 906 patients had measurable disease at entry. At all measurement time points, complete response (CR), PR, and MR resulted in similar TTP and OS; this was also true for NC− and NC+, and for PD and subjective PD. Patients were subsequently classified as responders (CR/PR/MR), NC (NC+/NC−), or PD. This three-class response categorization was found to be highly predictive of further progression or survival for the first two measurement points. After 6 months of imatinib, responders (CR/PR/MR) had the same survival prognosis as patients classified as NC.

Conclusion

RECIST perfectly enables early discrimination between patients who benefited long term from imatinib and those who did not. After 6 months of imatinib, if the patient is not experiencing PD, the pattern of radiologic response by tumor size criteria has no prognostic value for further outcome. Imatinib needs to be continued as long as there is no progression according to RECIST.
The Impact of the Privacy Rule on Cancer Research: Variations in Attitudes and Application of Regulatory Standards
Authors: Goss Elizabeth , Link Michael P. , Bruinooge Suanna S. , Lawrence Theodore S. , Tepper Joel E. , Runowicz Carolyn D. , Schilsky Richard L.
Published: July 2009

Purpose

The American Society of Clinical Oncology (ASCO) Cancer Research Committee designed a qualitative research project to assess the attitudes of cancer researchers and compliance officials regarding compliance with the US Privacy Rule and to identify potential strategies for eliminating perceived or real barriers to achieving compliance.

Methods

A team of three interviewers asked 27 individuals (13 investigators and 14 compliance officials) from 13 institutions to describe the anticipated approach of their institutions to Privacy Rule compliance in three hypothetical research studies.

Results

The interviews revealed that although researchers and compliance officials share the view that patients' cancer diagnoses should enjoy a high level of privacy protection, there are significant tensions between the two groups related to the proper standards for compliance necessary to protect patients. The disagreements are seen most clearly with regard to the appropriate definition of a “future research use” of protected health information in biospecimen and data repositories and the standards for a waiver of authorization for disclosure and use of such data.

Conclusion

ASCO believes that disagreements related to compliance and the resulting delays in certain projects and abandonment of others might be eased by additional institutional training programs and consultation on Privacy Rule issues during study design. ASCO also proposes the development of best practices documents to guide 1) creation of data repositories, 2) disclosure and use of data from such repositories, and 3) the design of survivorship and genetics studies.
Removal of a ribosome small subunit-dependent GTPase confers salt resistance on Escherichia coli cells
Authors: Hase Yoichi , Yokoyama Shinichiro , Muto Akira , Himeno Hyouta
Published: July 2009

RsgA is a unique GTP hydrolytic protein in which GTPase activity is significantly enhanced by the small ribosomal subunit. Deletion of RsgA causes slow cell growth as well as defects in subunit assembly of the ribosome and 16S rRNA processing, suggesting its involvement in maturation of the small subunit. In this study, we found that removal of RsgA or inactivation of its ribosome small subunit-dependent GTPase activity provides Escherichia coli cells with resistance to high salt stress. Salt stress suppressed the defects in subunit assembly of the ribosome and processing of 16S rRNA as well as truncation of the 3′ end of 16S rRNA in RsgA-deletion cells. In contrast, salt stress transiently impaired subunit assembly of the ribosome and processing of 16S rRNA and induced 3′ truncation of 16S rRNA in wild-type cells. These results suggest that the action of RsgA on the ribosome, which usually facilitates maturation of the small subunit, disturbs it under a salt stress condition. Consistently, there was a drastic but transient decrease in the intracellular amount of RsgA after salt shock. Salt shock would make the pathway of maturation of the ribosome small subunit RsgA independent.
A Branch-and-Price Approach to the Share-of-Choice Product Line Design Problem
Authors: Wang Xinfang (Jocelyn) , Camm Jeffrey D. , Curry David J.
Published: July 2009

We develop a branch-and-price algorithm for constructing an optimal product line using partworth estimates from choice-based conjoint analysis. The algorithm determines the specific attribute levels for each multiattribute product in a set of products to maximize the resulting product line's share of choice, i.e., the number of respondents for whom at least one new product's utility exceeds the respondent's reservation utility. Computational results using large commercial and simulated data sets demonstrate that the algorithm can identify provably optimal, robust solutions to realistically sized problems.
The interaction of attention and action: From seeing action to acting on perception
Authors: Humphreys Glyn W. , Yoon Eun Young , Kumar Sanjay , Lestou Vaia , Kitadono Keiko , Roberts Katherine L. , Riddoch M. Jane
Published: July 2009

We discuss evidence indicating that human visual attention is strongly modulated by the potential of objects for action. The possibility of action between multiple objects enables the objects to be attended as a single group, and the fit between individual objects in a group and the action that can be performed influences responses to group members. In addition, having a goal state to perform a particular action affects the stimuli that are selected along with the features and area of space that is attended. These effects of action may reflect statistical learning between environmental cues that are linked by action and/or the coupling between perception and action systems in the brain. The data support the argument that visual selection is a flexible process that emerges as a need to prioritize objects for action.
The obscuring object of race: Clinical breast exams and coping styles in ethnic subpopulations of women
Authors: Kudadjie‐Gyamfi Elizabeth K. , Magai Carol , Consedine Nathan S.
Published: July 2009

Objectives. Differences in breast cancer screening rates have been linked to many factors including race, access to healthcare, and breast cancer knowledge and beliefs; less frequently studied has been the role of characteristic styles of coping. In this study, we examined ethnicity and the role of coping with a possible breast cancer diagnosis in the context of whether or not women obtained clinical breast examinations (CBE).

Design. To measure coping, a stressor, in the form of a vignette asking participants to imagine they had just received a breast diagnosis upon a doctor's visit, was used.

Method. Three hundred and eight women from seven ethnic subpopulations (and from three racial groups) in the USA were interviewed regarding frequency of breast screening, as well as how they would likely cope with a diagnosis of breast cancer.

Results. CBE rates were similar across groups and were differentially predicted by the different coping styles. Analysing the results using typical racial categories (rather than distinct ethnic groupings) obscured these results. Furthermore, avoidance predicted CBE and mammogram rates differently, specifically, predicting mammogram rates differentially for each group, with no relation to CBE rates.

Conclusion. Recognition of the roles of problem solving, social support, and avoidance in coping with a possible breast cancer diagnosis may guide the development and provision of interventions that are more sensitive to the characteristics of specific groups of women. Examinations of psychological variables in preventive health behaviours must begin to analyse diversity by paying attention to ethnic specificity, rather than race, as well as to the underlying nature of the screening task.
Self‐reported health, self‐reported fitness, and all‐cause mortality: Prospective cohort study
Authors: Phillips Anna C. , Der Geoff , Carroll Douglas
Published: July 2009

Objectives. Self‐reported health has a well established relationship to later mortality, although the reasons are not entirely understood. This study examined the association of a similar self‐reported measure of fitness with mortality and compared it to that of self‐reported health.

Design. The study had a prospective cohort design with multiple sampling points.

Methods. Participants were 858 men and women from Glasgow and the surrounding area of Scotland, aged 59 when self‐reported health and fitness data were first collected in 1991/92. They were re‐interviewed at age 64 and 69 and mortality was tracked for 16.5 years in total. Hazard ratios for all cause mortality were estimated for those that reported poor health or poor fitness relative to others their age, taking into account a range of covariates, some of which were also time varying.

Results. In both unadjusted and covariate adjusted models, self‐reported fitness was at least as good a predictor of mortality as self‐reported health. In a mutually adjusted model, both again emerged as significant predictors. Poor subjective health with poor subjective fitness appeared to be a particularly lethal combination.

Conclusion. Both self‐reported health and self‐reported fitness were independent predictors of mortality. Where the objective assessment of aerobic fitness is not feasible, a simple measure of subjective fitness could prove a useful alternative.
Quantitative evidence for distinct cognitive impairment in anorexia nervosa and bulimia nervosa
Authors: Zakzanis Konstantine K. , Campbell Zachariah , Polsinelli Angelina
Published: July 2009

It is generally agreed that at least some aspects of abnormal eating behaviour is indeed due in part to disordered cognition. The accumulated literature illustrates cognitive impairment in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Yet beyond being inconsistent, these independent studies also do not reveal the magnitude of impairment within and across studies and fail to give due consideration to the magnitude of impairment so as to understand the severity and breadth of impairment and/or differences in cognitive profiles between patients with AN and BN. Hence, the present review on the subject sought to articulate the magnitude of cognitive impairment in patients with AN and BN by quantitatively synthesizing the existing literature using meta‐analytic methodology. The results demonstrate modest evidence of cognitive impairment specific to AN and BN that is related to body mass index in AN in terms of its severity, and is differentially impaired between disorders. Together, these results suggest that disturbed cognition is figural in the presentation of eating disorders and may serve to play an integral role in its cause and maintenance. Implications of these findings with respects to future research are discussed.
Induction of Periostin-like Factor and Periostin in Forearm Muscle, Tendon, and Nerve in an Animal Model of Work-related Musculoskeletal Disorder
Authors: Rani Shobha , Barbe Mary F. , Barr Ann E. , Litvin Judith
Published: July 2009

Work-related musculoskeletal disorders (WMSDs), also known as repetitive strain injuries of the upper extremity, frequently cause disability and impairment of the upper extremities. Histopathological changes including excess collagen deposition around myofibers, cell necrosis, inflammatory cell infiltration, and increased cytokine expression result from eccentric exercise, forced lengthening, exertion-induced injury, and repetitive strain-induced injury of muscles. Repetitive tasks have also been shown to result in tendon and neural injuries, with subsequent chronic inflammatory responses, followed by residual fibrosis. To identify mechanisms that regulate tissue repair in WMSDs, we investigated the induction of periostin-like factor (PLF) and periostin, proteins induced in other pathologies but not expressed in normal adult tissue. In this study, we examined the level of PLF and periostin in muscle, tendon, and nerve using immunohistochemistry and Western blot analysis. PLF increased with continued task performance, whereas periostin was constitutively expressed. PLF was located in satellite cells and/or myoblasts, which increased in number with continued task performance, supporting our hypothesis that PLF plays a role in muscle repair or regeneration. Periostin, on the other hand, was not present in satellite cells and/or myoblasts.
Tribocharging of Particle Contaminants Evaluated as an Ignition Source in Oxygen-Enriched Environments
Authors: Oza Aditi , Ghosh Sudipto , Chowdhury Kanchan
Published: July 2009

Contamination particles make an oxygen system more vulnerable to fire hazard as they provide a large surface area with reduced minimum energy of ignition. Adiabatic compression, resonance, solid friction, flow friction, and promoted ignition have acted as the source of ignition in oxygen systems. In this paper, static electricity generated in solid particles is proposed to be another possible source of ignition. It is known that the movement of particles in a system results in the buildup of static charges in them. This static electricity, if supported by suitable geometric configuration and grounding of metal projections, may lead to propagating brush discharge (PBD) and provide the energy needed for initiation of fire. Particles with low auto-ignition temperature, particularly in dispersed state, may help in initiating the fire, while metal particles may aid the propagation because of their high combustion energy. In this paper, we have determined the velocity profile utilizing the FLUENT code and calculated the charge generated in particles, exploring the ignition probability of equipment in oxygen environment through electrostatic discharge. We have also attempted to perform preliminary calculation to determine charge density and the electric field strength required for brush discharge. Computational fluid dynamics analyses on globe valves reveal the presence of probable areas of particulate accumulation in the valve. The decrease in minimum ignition energy (MIE) in the environment of high pressure, high temperature, high purity of oxygen, low humidity, small particles, high dielectric constant, low thickness of insulating layer, and high resistance of the deposited dust layer facilitates occurrence of PBD, which may cause ignition. Adiabatic heating may aid combustion by lowering the MIE of particles. Experiments have been proposed for verification of the hypothesis and analytical calculations presented by the authors. The paper may give a new insight into the possible causes of oxygen fire.
Additive Genetic Variability and the Bayesian Alphabet
Authors: Gianola Daniel , de los Campos Gustavo , Hill William G , Manfredi Eduardo , Fernando Rohan
Published: July 2009

The use of all available molecular markers in statistical models for prediction of quantitative traits has led to what could be termed a genomic-assisted selection paradigm in animal and plant breeding. This article provides a critical review of some theoretical and statistical concepts in the context of genomic-assisted genetic evaluation of animals and crops. First, relationships between the (Bayesian) variance of marker effects in some regression models and additive genetic variance are examined under standard assumptions. Second, the connection between marker genotypes and resemblance between relatives is explored, and linkages between a marker-based model and the infinitesimal model are reviewed. Third, issues associated with the use of Bayesian models for marker-assisted selection, with a focus on the role of the priors, are examined from a theoretical angle. The sensitivity of a Bayesian specification that has been proposed (called “Bayes A”) with respect to priors is illustrated with a simulation. Methods that can solve potential shortcomings of some of these Bayesian regression procedures are discussed briefly.
The Complex Tale of the achaete–scute Complex: A Paradigmatic Case in the Analysis of Gene Organization and Function During Development
Authors: García-Bellido Antonio , de Celis Jose F
Published: July 2009

The achaete–scute gene complex (AS-C) contains four genes encoding transcription factors of the bHLH family, achaete, scute, lethal of scute, and asense located in 40 kb of DNA containing multiple cis-regulatory position-specific enhancers. These genes play a key role in the commitment of epidermal cells toward a neural fate, promoting the formation of both sensory organs in the peripheral nervous system (bristles) of the adult and of neuroblasts in the central nervous system of the embryo. The analysis of the AS-C initially focused on the variations in positional specificity of effects of achaete (ac) and scute (sc) alleles on macrochaete bristle pattern in the Drosophila adult epidermis, and from there it evolved as a key entry point into understanding the molecular bases of pattern formation and cell commitment. In this perspective, we describe how the study of the AS-C has contributed to the understanding of eukaryotic gene organization and the dissection of the developmental mechanisms underlying pattern formation.
Expanded Newborn Screening: Outcome in Screened and Unscreened Patients at Age 6 Years
Authors: Wilcken Bridget , Haas Marion , Joy Pamela , Wiley Veronica , Bowling Francis , Carpenter Kevin , Christodoulou John , Cowley David , Ellaway Carolyn , Fletcher Janice , Kirk Edwin P. , Lewis Barry , McGill Jim , Peters Heidi , Pitt James , Ranieri Enzo , Yaplito-Lee Joy , Boneh Avihu
Published: July 2009

OBJECTIVE: Tandem mass spectrometry is widely applied to routine newborn screening but there are no long-term studies of outcome. We studied the clinical outcome at six years of age in Australia.

METHODS: In a cohort study, we analyzed the outcome at 6 years for patients detected by screening or by clinical diagnosis among >2 million infants born from 1994 to 1998 (1 017 800, all unscreened) and 1998 to 2002 (461 500 screened, 533 400 unscreened) recording intellectual and physical condition, school placement, other medical problems, growth, treatment, diet, and hospital admissions. Results were analyzed separately for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and other disorders, and grouped patients as those who presented clinically or died in the first 5 days of life; patients presented later or diagnosed by screening, and those with substantially benign disorders.

RESULTS: Inborn errors, excluding phenylketonuria, were diagnosed in 116 of 1 551 200 unscreened infants (7.5/100 000 births) and 70 of 461 500 screened infants (15.2/100 000 births). Excluding MCADD, 21 unscreened patients with metabolic disorders diagnosed after 5 days of life died or had a significant intellectual or physical handicap (1.35/100 000 population) compared with 2 of the screened cohort (0.43/100 000; odds ratio: 3.1 [95% CI: 0.73–13.32]). Considering the likely morbidity or mortality among the expected number of never-diagnosed unscreened patients, there would be a significant difference. Growth distribution was normal in all cohorts.

CONCLUSION: Screening by tandem mass spectrometry provides a better outcome for patients at 6 years of age, with fewer deaths and fewer clinically significant disabilities.
Screening for Type 2 Diabetes in Obese Youth
Authors: Shah Shuchi , Kublaoui Bassil M. , Oden Jon D. , White Perrin C.
Published: July 2009

OBJECTIVE: To assess available blood tests as potential screening tools for impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM).

METHODS: We studied 468 obese (BMI mean: 34.4 kg/m2) children, including a subgroup with serum fasting insulin levels of >15 μIU/mL. Fasting laboratory tests included measurements of serum glucose and insulin, hemoglobin A1c (HbA1c), and 1,5-anhydroglucitol (insulin-resistant subgroup only) levels. An oral glucose-tolerance test was performed on each patient, and 2-hour postload serum glucose and insulin levels were obtained. Fasting blood glucose (BG), Homeostasis Model of Assessment for Insulin Resistance (HOMA-IR), HbA1c, and 1,5-anhydroglucitol values were used as predictors for exceeding various 2-hour BG cut-offs. Receiver operator characteristic curves were fitted to determine area-under-the-curve values as measures of screening efficacy.

RESULTS: In the insulin-resistant subgroup, 3 (2%) patients had T2DM and 23 (12%) had IGT. Optimal sensitivity and specificity to detect T2DM were, respectively, 99% and 96% at HbA1c ≥ 6.0%, and 96% and 88% at 1,5-anhydroglucitol < 17.0 μg/mL, with lower values for fasting BG and the HOMA-IR. In the entire study group, 9 (2%) patients had T2DM and 44 (9%) had IGT. Optimal sensitivity and specificity to detect T2DM were, respectively, 86% and 85% at HbA1c levels of 5.7%, 88%, and 93% at a fasting BG level of 104 mg/dL, and 62% and 70% at an HOMA-IR of 7.9.

CONCLUSIONS: HbA1c, 1,5-anhydroglucitol, and fasting BG levels are good predictors of T2DM in obese children, whereas HOMA-IR values are not. HbA1c and 1,5-anhydroglucitol are excellent predictors of T2DM in insulin-resistant obese children.
Parenting Attitudes and Infant Spanking: The Influence of Childhood Experiences
Authors: Chung Esther K. , Mathew Leny , Rothkopf Amy C. , Elo Irma T. , Coyne James C. , Culhane Jennifer F.
Published: July 2009

OBJECTIVES: To assess associations among maternal childhood experiences and subsequent parenting attitudes and use of infant spanking (IS), and determine if attitudes mediate the association between physical abuse exposure and IS.

METHODS: We performed a prospective study of women who received prenatal care at community health centers in Philadelphia, Pennsylvania. Sociodemographic characteristics, adverse childhood experiences (ACEs), attitudes toward corporal punishment (CP), and IS use were assessed via face-to-face interviews, conducted at the first prenatal care visit, 3 months postpartum, and 11 months postpartum. Bivariate and multiple logistic regression analyses were conducted.

RESULTS: The sample consisted of 1265 mostly black, low-income women. Nineteen percent of the participants valued CP as a means of discipline, and 14% reported IS use. Mothers exposed to childhood physical abuse and verbal hostility were more likely to report IS use than those not exposed (16% vs 10%, P = .002; 17% vs 12%, P = .02, respectively). In the adjusted analyses, maternal exposure to physical abuse, other ACEs, and valuing CP were independently associated with IS use. Attitudes that value CP did not mediate these associations.

CONCLUSIONS: Mothers who had childhood experiences of violence were more likely to use IS than mothers without such experiences. Intergenerational transmission of CP was evident. Mothers who had experienced physical abuse as a child, when compared to those who had not, were 1.5 times more likely to use IS. Child discipline attitudes and maternal childhood experiences should be discussed early in parenting in order to prevent IS use, particularly among at-risk mothers.
Pregabalin: A New Approach to Treatment of the Dysautonomic Crisis
Authors: Axelrod Felicia B. , Berlin Dena
Published: July 2009

Nausea and dysautonomic crises severely limit function and quality of life for a large number of individuals with familial dysautonomia. We treated a small cohort of 15 patients with familial dysautonomia who suffered frequent dysautonomic crises with pregabalin. Nausea and overt crises markedly decreased in 13 (87%) of these patients and the overall assessments of benefit were extremely favorable, suggesting that pregabalin may be a potentially useful therapeutic agent for this disorder.
Delayed Recognition of Initial Stroke in Children: Need for Increased Awareness
Authors: Srinivasan Jayasri , Miller Steven P. , Phan Thanh G. , Mackay Mark T.
Published: July 2009

OBJECTIVE: The goal was to identify the delays involved in diagnosing pediatric arterial ischemic stroke (AIS), a major cause of morbidity and death in children.

METHODS: Neonates (≤28 days of age) and children with a first presentation of radiologically confirmed AIS between June 1993 and January 2006 were identified retrospectively. The time to diagnosis of AIS (ie, time from clinical onset to radiologic confirmation) was calculated, and factors influencing stroke diagnosis were reviewed.

RESULTS: A total of 107 patients (19 neonates and 88 children) with a diagnosis of AIS were identified. The median time to AIS diagnosis was 87.9 hours for neonates, significantly longer than 24.8 hours for children (P = .0002). Sixty-nine percent of the children with AIS demonstrated a likely cardioembolic cause, and 51 (58%) of the 88 children were inpatients at the time of stroke. The inpatients were seen by a physician more quickly (P < .01) and received a diagnosis of AIS sooner (P < .01). Seventy-six (86%) of the 88 children had a focal neurologic deficit when first seen by a physician. Physicians documented a diagnosis/differential diagnosis for 44 (50%) of 88 children, and they documented a suspicion of AIS for only 23 (26%) of 88 children. The presence of seizures or focal signs was not associated with a quicker time to stroke confirmation.

CONCLUSIONS: The considerable delays in the diagnosis of pediatric AIS are most likely related to the lack of awareness of stroke among medical staff members, despite risk factors and focal signs at presentation.
Practice of Feeding Premasticated Food to Infants: A Potential Risk Factor for HIV Transmission
Authors: Gaur Aditya H. , Dominguez Kenneth L. , Kalish Marcia L. , Rivera-Hernandez Delia , Donohoe Marion , Brooks John T. , Mitchell Charles D.
Published: July 2009

OBJECTIVES: Although some caregivers are known to premasticate food for infants, usually during the weaning period, HIV transmission has not been linked to this practice. We describe 3 cases of HIV transmission in the United States possibly related to this practice.

PATIENTS AND METHODS: Three cases of HIV infection were diagnosed in children at ages 9, 15, and 39 months; clinical symptomatology prompted the testing. A thorough investigation to rule out alternative modes of transmission was conducted. In addition, phylogenetic comparisons of virus from cases and suspected sources were performed by using the C2V3C3 or gp41 region of env and the p17 coding region of gag.

RESULTS: In 2 cases, the mothers were known to be infected with HIV, had not breastfed their children, and perinatal transmission of HIV had previously been ruled out following US HIV testing guidelines. In the third case, a great aunt who helped care for the child was infected with HIV, but the child's mother was not. All 3 children were fed food on multiple occasions that had been premasticated by a care provider infected with HIV; in 2 cases concurrent oral bleeding in the premasticating adult was described. Phylogenetic analyses supported the epidemiologic conclusion that the children were infected through exposure to premasticated food from a caregiver infected with HIV in 2 of the 3 cases.

CONCLUSIONS: The reported cases provide compelling evidence linking premastication to HIV infection, a route of transmission not previously reported that has important global implications including being a possible explanation for some of the reported cases of “late” HIV transmission in infants, so far attributed to breastfeeding. Until the risk of premastication and modifying factors (eg, periodontal disease) are better understood, we recommend that health care providers routinely query children's caregivers and expecting parents who are infected with HIV or at risk of HIV infection about this feeding practice and direct them to safer, locally available, feeding options.
A Videolaryngoscopy Technique for the Intubation of the Newborn: Preliminary Report
Authors: Vanderhal Andre L. , Berci George , Simmons Charles F. , Hagiike Masanobu
Published: July 2009

OBJECTIVE: We describe videolaryngoscopy equipment and technique for endotracheal intubation and airway evaluation in the delivery room (DR) and NICU for endotracheal intubation and airway evaluation. We report our first experience of 47 patients.

METHODS: Forty-seven infants who weighed 530 to 6795 g and required endotracheal intubation or airway evaluation were considered for intubation or assessment by using the modified Kaplan-Berci videolaryngoscope. We report quality-improvement data after initial introduction of newly approved technology.

RESULTS: We report results of 48 intubations in 42 patients and videolaryngoscopic inspection without intubation in 5 patients. Five intubation attempts were successful after failed attempts by experienced intubators; 6 attempts by residents were completed with video guidance rather than requiring an additional attempt. Only 3 intubations required more than 2 attempts. Enlarged panoramic view and recording assisted in correct diagnosis of vocal cord paralysis. The features and main advantages are discussed in detail. No complications or difficulties resulting from the technology occurred.

CONCLUSIONS: This new technique and technology show promise to improve airway management, evaluation, and teaching. Future research to validate improved intubation success in difficult airways and in teaching situations is warranted.