bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy and Narcolepsy-Cataplexy in a Child
Authors: Yang Zhixian , Liu Xiaoyan , Dong Xiaosong , Qin Jiong , Li Jing , Han Fang
Published: May 2012

We report a 5-year-old boy with epilepsy and narcolepsy-cataplexy. He developed myoclonic seizures at the age of 4 years, which manifested as head shaking to the left. Approximately 6 months later, narcolepsy-cataplexy with excessive daytime sleepiness occurred. Although a short-time electroencephalography (EEG) and 24-hour ambulatory EEG monitoring found epileptiform discharges, no seizures were determined. Oxcarbazepine was used and led to increased attacks. Video EEG testing finally confirmed the diagnosis of epilepsy; therefore, valproate was given and seizures were controlled completely. Typical cataplexy triggered by laughing, together with the positive multiple sleep latency tests confirmed a diagnosis of narcolepsy-cataplexy. Human leukocyte antigens DQB1*0602 was positive, and the hypocretin level in cerebrospinal fluid was found to be decreased. Combination of valproate, methylphenidate, and clomipramine treatment improved the symptoms of both narcolepsy-cataplexy and seizure. The coexistence of both disorders in this single patient indicated that there might be a common mechanism between epilepsy and narcolepsy-cataplexy.
Bell Palsy in a Neonate With Rapid Response to Oral Corticosteroids
Authors: Saini Arushi , Singhi Pratibha , Sodhi K. S. , Gupta Ajit
Published: May 2012

Idiopathic facial nerve palsy, also known as Bell palsy is rare in the neonatal age group. Other more common causes such as birth trauma; infections, especially otitis media; and congenital malformations need to be excluded. We present here a 4-week-old neonate with Bell palsy who responded rapidly to oral corticosteroids. Such an early presentation of idiopathic facial nerve palsy and use of corticosteroids in neonates is scarcely reported in the literature.
FSW of AA2139-T8 Butt joints for aeronautical applications
Authors: Campanile G , Prisco A , Squillace A , Bitondo C , Dionoro G , Buonadonna P , Tronci A , Fratini L , Palmeri D
Published: May 2012

The effect of process parameters on mechanical and microstructural properties of AA 2139 T8 joints produced by friction stir welding (FSW) was analysed by means of statistical tools. Three different parameters were taken into account: angular speed ( ω), welding speed ( va), and plunging depth ( p); each of them was varied on three levels. Forces and temperatures achieved during the welding were monitored and analysed for all joints. An accurate microstructural analysis was performed: the occurrence of some remarkable defects, typical of FSW, such as tunnel or lack of penetration, was related to actual process parameters adopted. The extension of each FSW characteristic zone was measured and the main grain dimension within each of these zones was measured. The mechanical properties of the joints were evaluated by means of Vickers microhardness measurements and tensile tests at room temperature. It was observed that the joint welded with lowest angular speed, highest welding speed, and greatest plunging depth attained the best performances. The statistical data treatment allowed providing a numerical model capable of predicting the mechanical performances of joints.
Telling the Right Hand From the Left Hand
Authors: Viswanathan Shivakumar , Fritz Courtney , Grafton Scott T.
Published: May 2012

Judging the laterality of a hand seen at unanticipated orientations evokes a robust feeling of bodily movement, even though no movement is produced. In two experiments, we tested a novel hypothesis to explain this phenomenon: A hand’s laterality is determined via a multisensory binding of the visual representation of the seen hand and a proprioceptive representation of the observer’s felt hand, and the felt “movement” is an obligatory aftereffect of intersensory recalibration. Consistent with the predictions implied by such a cross-modal mechanism, our results in Experiment 1 showed that manipulating observers’ selective attention can evoke illusory feelings of movement in the “wrong” hand (i.e., the hand whose laterality does not match that of the stimulus). In Experiment 2, these illusions were readily extinguished in conditions in which binding was predicted to fail, a result indicating that cross-modal binding was necessary to produce them. These results are not explained by imagery, a mechanism widely assumed to account for how hand laterality is identified.
Semantic Priming From Crowded Words
Authors: Yeh Su-Ling , He Sheng , Cavanagh Patrick
Published: May 2012

Vision in a cluttered scene is extremely inefficient. This damaging effect of clutter, known as crowding, affects many aspects of visual processing (e.g., reading speed). We examined observers’ processing of crowded targets in a lexical decision task, using single-character Chinese words that are compact but carry semantic meaning. Despite being unrecognizable and indistinguishable from matched nonwords, crowded prime words still generated robust semantic-priming effects on lexical decisions for test words presented in isolation. Indeed, the semantic-priming effect of crowded primes was similar to that of uncrowded primes. These findings show that the meanings of words survive crowding even when the identities of the words do not, suggesting that crowding does not prevent semantic activation, a process that may have evolved in the context of a cluttered visual environment.
Reliability and Validity of the Malay International Physical Activity Questionnaire (IPAQ-M)Among a Malay Population in Malaysia
Authors: Chu Anne Hin Yee , Moy Foong Ming
Published: May 2012

The International Physical Activity Questionnaire (IPAQ) was developed to assess the physical activity patterns in populations. The authors aim to examine the reliability and validity of the Malay version of IPAQ (IPAQ-M). The IPAQ-M was self-administered twice at a 1-week interval to assess its test–retest reliability. Criterion validity was assessed between the IPAQ-M and a 7-day physical activity log (PA-Log). A total of 81 Malay adults participated in the study. Intraclass correlation coefficients (ICC), kappa (κ), correlation coefficients (ρ), and Bland–Altman plot were used for data analyses. The ICC scores revealed moderate to good correlations (ICC = 0.54-0.92; P < .001) on items categorized by intensities and domains and a κ of 0.73 for total activity. Validity results from the PA-Log were statistically significant ( P < .001) across intensities and domains (ρ = 0.67-0.98). The IPAQ-M demonstrated good reliability and validity for the evaluation of physical activity among this Malay population.
Handling scenarios complexity in model-based design
Authors: Aboutaleb Hycham , Boutin Samuel , Monsuez Bruno
Published: May 2012

Given that most large-scale complex engineering systems need to be simplified and layered before being designed, a hierarchical approach is necessary to ensure a global and structured understanding of the whole system, including involved stakeholders, use cases, and associated requirements. Even though use cases in themselves are quite intuitive, the process around them is a much bigger challenge since it usually varies from one situation to another. The key step in the proposed methodology is the identification of the system dimensions as a mean to organize use cases. In this article, we propose a framework to address the system dimensions by defining useful functional spaces and accordingly classify the scenarios. As a case study, we analyze and model a cooperative intersection safety system using a hierarchical method to represent use cases. The key challenge in enhancing intersection safety is to identify vehicles that have a high potential to be involved in a collision as early as possible and take preventive action thereof. Such a system design and implementation needs an analysis phase during which the system to design and its environment are analyzed and decomposed. This approach simplifies the understanding of the intersection crossing problem by applying transformations that reduce its complexity. It begins with a thorough analysis of accidents at intersections and providing the main characteristics of these accidents. From the type and severity of accident scenarios, a classification of relevant scenarios is made. The proposed methodology establishes a strong and intuitive link between use cases on one hand and requirements and functional architecture on the other. Moreover, coherency is increased as the hierarchy of use cases affects the hierarchy in functional architecture.
Bright Light Therapy to Promote Sleep in Mothers of Low-Birth-Weight Infants
Authors: Lee Shih-Yu , Aycock, Dawn M. , Moloney Margaret F.
Published: May 2012

Having a low-birth-weight (LBW) infant in a neonatal intensive care unit (NICU) can intensify a mother’s sleep disturbances due to both stress and the dim lighting in the ICU setting, which desynchronizes circadian rhythms. The purpose of this pilot study was to examine the effectiveness of a 3-week bright light therapy intervention on sleep and health outcomes of mothers with LBW infants in the NICU. Controlled stratified randomization was used to assign 30 mothers to a treatment or control group. Data were collected at pretreatment (second week postpartum) and after the 3-week intervention. Sleep data were assessed by wrist actigraph (total sleep time [TST], circadian activity rhythms [CARs]) and the General Sleep Disturbance scale. Other outcome variables were measured by the Lee’s Fatigue scale, Edinburgh Postpartum Depression scale, and the Medical Outcomes Short Form 36, version 2. Mothers averaged 26.6 ( SD = 6.3) years of age, and the majority were Black (73%). The mean gestational age for the infants was 27.7 ( SD = 2.0) weeks. Small to large effect sizes were found when comparing the pre- to posttreatment differences between groups. Although none of the differences were statistically significant in this small sample, for mothers in the treatment group nocturnal TST ( d = .33), CAR ( d = 1.06), morning fatigue ( d = .22), depressive symptoms ( d = .40), physical health–related quality of life ( d = .33), and mental health–related quality of life ( d = .60) all improved compared to the control group. Bright light therapy is feasible for mothers with infants in an NICU. Clinically significant improvements have been evidenced; a larger-scale trial of effectiveness is needed.
A Comparison of the Effects of Fixed- and Rotating-Shift Schedules on Nursing Staff Attention Levels
Authors: Niu Shu-Fen , Chu Hsin , Chen Chiung-Hua , Chung Min-Huey , Chang Yu-Shiun , Liao Yuan-Mei , Chou Kuei-Ru
Published: May 2012

Purpose:

Sleep deficit affects neurobehavioral functioning, reduces attention and cognitive function, and negatively impacts occupational safety. This study investigated selective attention levels of nursing staff on different shifts.

Methods:

Using a prospective, randomized parallel group study, selective attention was measured using the d2 test in 62 nursing staff in a medical center in Taiwan.

Findings:

There were significant differences in selective attention indicators (E%) between the fixed-day-shift group (control group) and rotating-shift group (experimental group): The percentage of errors (E%) for night-shift workers in the rotating-shift group was higher than that of fixed-day-shift workers, while the total number of items scanned minus error (TN − E) and concentration performance (CP) scores were higher for fixed-day-shift workers. Within the experimental group, the error rate on night shift was 0.44 times more than that on day shift and .62 times more than on evening shift; the TN-E on night shift was 38.99 items less than that on day shift, and the CP was 27.68 items less on night shift than on day shift; indicating that staff on the night shift demonstrated poorer speed and accuracy on the overall test than did the staff on day shifts.

Conclusions:

Inadequate sleep and a state of somnolence adversely affected the attention and operation speed of work among night-shift workers. More than 2 days off is suggested when shifting from the night shift to other shifts to provide adequate time for circadian rhythms to adjust.
Changes in Regional Communities
Authors: Byun Jongim , Ryu Kiung
Published: May 2012

The Problem.

Although the promises advanced by promoting Korea’s Lifelong Learning City Project by the municipal governments are relevant to the development of regional human resources and the local community capacity, we know little about how or whether the project leads to substantive and sustainable changes. This study seeks to examine how the concept of organization development (OD) can be linked with lifelong learning cities, how the development of human resources is being accomplished in the learning cities, and how residents contribute to local communities as well as how they bring about changes in their local communities.

The Solution.

This study indicates that the theoretical and practical aspects of OD can be applied to many other contexts such as government organizations, planned change efforts for communities, and society.

The Stakeholders.

This study’s findings concern adult educators, practitioners, and scholars in human resource development for societal development.
Minocycline-Induced Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome
Authors: Taylor Jamie L. , Kulkarni Mona S. , Behringer Elizabeth C. , Yusufali Taizoon , Trento Alfredo , D’Attellis Nicola P.
Published: May 2012

This article reports a case of minocycline-induced drug reaction with eosinophilia and systemic symptoms syndrome in a 16-year-old female who presented with acute myocarditis and severe heart failure. Drug reaction with eosinophilia and systemic symptoms syndrome is a severe, multisystem reaction. It is usually manifested by cutaneous, lymphatic, and solid organ involvement with progression to multisystem organ failure, following the use of several medications. There are 3 previous documented reports of drug reaction with eosinophilia and systemic symptoms syndrome–induced myocarditis. This is a case report and a review of the literature.
Care of the Organ Donor in the ICU
Authors: Swain Sharon , Sardella Brian
Published: May 2012

The number of patients awaiting a solid organ transplant in the United States continues to grow each year despite efforts to increase the donor pool. Because only 1% of all deaths in the United States may become eligible as organ donors, the preservation of donors and the maximum number of organs from each donor is essential. Optimal organ procurement rests on the principles of early identification of potential donors, timely family- and patient-centric discussion of the option for organ donation and then careful donor management up to and through the procurement process. Health care practitioners in the ICU play important roles at each step of this process. This article outlines the basic considerations for optimizing organ quality during the donation process.
Community Capacity Building for Health
Authors: Traverso-Yepez Martha , Maddalena Victor , Bavington William , Donovan Catherine
Published: May 2012

There is a great deal of literature examining the benefits and relevance of community participation and community capacity building in health promotion and disease prevention endeavors. Academic literature embracing principles and commitment to community participation in health promotion practices often neglects the complexities involved and the flexibility required to work within this approach. This article addresses some of these challenges through a case study of two projects funded by Provincial Wellness Grants in Newfoundland and Labrador, a province in Canada with a strong tradition of community ties and support systems. In addition to addressing the unique circumstances of the community groups, this research allowed the authors to examine the situational context and power relations involved in the provision of services as well as the particular forms of subjectivity and citizenship that the institutional practices support. Recognizing this complex interdependency is an important step in creating more effective intervention practices.
A Case Study of the Common Difficulties Experienced by High School Students in Chemistry Classroom in Gilgit-Baltistan (Pakistan)
Authors: Ali Takbir
Published: May 2012

This article reports a research study conducted with four chemistry teachers in three high schools (two government schools and one private school) in Gilgit-Baltistan region of Pakistan. The study investigated questions concerning common difficulties high school (Grades 9 and 10) students experience in chemistry classroom, the possible reasons for these difficulties, and the ways in which teachers help students overcome these difficulties. A qualitative case study method was used to investigate the questions, which used in-depth interviews with teachers, classroom observation, and postobservation discussion with the teachers, as main data collection tools. The key findings of the study allude to a huge gap between what is intended in the National Curriculum in terms of students’ learning in chemistry and what actually happens in the classroom where students learn chemistry. Promoting in-depth learning appeared to be an uphill task for the teachers. The main hurdle lies in students’ inability to demonstrate a good understanding of very basic concepts of the subject. Despite faced with such a challenge, the teachers appear to be committed to teaching their subject. The implications of the results of the study are explained in the context of schools, teachers, and other educational stakeholders by emphasizing the need for synchronization and integration of efforts on the part of schools.
Developing Effective Clinical Trainers
Authors: Khamarko Kevin , Koester Kimberly A. , Bie Jennifer , Baron Robert B. , Myers Janet J.
Published: May 2012

Continuing education and training provides a means to improve performance among health care professionals (HCP). Research shows, however, that continuing professional education activities have inconsistent effects on HCP competence, performance, and patient health outcomes. Furthermore, the trainer’s role as a facilitator of knowledge translation (KT) has been understudied. To understand how clinical trainers support their trainees in translating what they learned into practice, we conducted 16 in-depth interviews with expert trainers. These interviews yielded a variety of KT-enhancing strategies, including tailoring training activities to their trainees’ needs. In addition, participants recommended trainers familiarize themselves with their trainees’ work environments, be able to identify their knowledge deficits, and devote time to provide trainees with post-training support. Creating an effective training, one that leads to transfer, requires active planning, communication, and command of the training topic by skilled trainers.
Expression of pair rule gene orthologs in the blastoderm of a myriapod: evidence for pair rule-like mechanisms?
Authors: Janssen Ralf , Damen Wim G M , Budd Graham E
Published: May 2012

Background

A hallmark of Drosophila segmentation is the stepwise subdivision of the body into smaller and smaller units, and finally into the segments. This is achieved by the function of the well-understood segmentation gene cascade. The first molecular sign of a segmented body appears with the action of the pair rule genes, which are expressed as transversal stripes in alternating segments. Drosophila development, however, is derived, and in most other arthropods only the anterior body is patterned (almost) simultaneously from a pre-existing field of cells; posterior segments are added sequentially from a posterior segment addition zone. A long-standing question is to what extent segmentation mechanisms known from Drosophila may be conserved in short-germ arthropods. Despite the derived developmental modes, it appears more likely that conserved mechanisms can be found in anterior patterning.

Results

Expression analysis of pair rule gene orthologs in the blastoderm of the pill millipede Glomeris marginata (Myriapoda: Diplopoda) suggests that these genes are generally involved in segmenting the anterior embryo. We find that the Glomeris pairberry-1 ( pby-1) gene is expressed in a pair rule pattern that is also found in insects and a chelicerate, the mite Tetraynchus urticae. Other Glomeris pair rule gene orthologs are expressed in double segment wide domains in the blastoderm, which at subsequent stages split into two stripes in adjacent segments.

Conclusions

The expression patterns of the millipede pair rule gene orthologs resemble pair rule patterning in Drosophila and other insects, and thus represent evidence for the presence of an ancestral pair rule-like mechanism in myriapods. We discuss the possibilities that blastoderm patterning may be conserved in long-germ and short-germ arthropods, and that a posterior double segmental mechanism may be present in short-germ arthropods.
An extracellular Staphylococcus epidermidis polysaccharide: relation to Polysaccharide Intercellular Adhesin and its implication in phagocytosis
Authors: Spiliopoulou Anastasia I , Krevvata Maria I , Kolonitsiou Fevronia , Harris Llinos G , Wilkinson Thomas S , Davies Angharad P , Dimitracopoulos Georgios O , Karamanos Nikos K , Mack Dietrich , Anastassiou Evangelos D
Published: May 2012

Background

The skin commensal and opportunistic pathogen Staphylococcus epidermidis is a leading cause of hospital-acquired and biomaterial-associated infections. The polysaccharide intercellular adhesin (PIA), a homoglycan composed of β-1,6-linked N-acetylglucosamine residues, synthesized by enzymes encoded in icaADBC is a major functional factor in biofilm accumulation, promoting virulence in experimental biomaterial-associated S. epidermidis infection. Extracellular mucous layer extracts of S. epidermidis contain another major polysaccharide, referred to as 20-kDa polysaccharide (20-kDaPS), composed mainly out of glucose, N-acetylglucosamine, and being partially sulfated. 20-kDaPS antiserum prevents adhesion of S. epidermidis on endothelial cells and development of experimental keratitis in rabbits. Here we provide experimental evidence that 20-kDaPS and PIA represent distinct molecules and that 20-kDaPS is implicated in endocytosis of S. epidermidis bacterial cells by human monocyte-derived macrophages.

Results

Analysis of 75 clinical coagulase-negative staphylococci from blood-cultures and central venous catheter tips indicated that 20-kDaPS is expressed exclusively in S. epidermidis but not in other coagulase-negative staphylococcal species. Tn917-insertion in various locations in icaADBC in mutants M10, M22, M23, and M24 of S. epidermidis 1457 are abolished for PIA synthesis, while 20-kDaPS expression appears unaltered as compared to wild-type strains using specific anti-PIA and anti-20-kDaPS antisera. While periodate oxidation and dispersin B treatments abolish immuno-reactivity and intercellular adhesive properties of PIA, no abrogative activity is exerted towards 20-kDaPS immunochemical reactivity following these treatments. PIA polysaccharide I-containing fractions eluting from Q-Sepharose were devoid of detectable 20-kDaPS using specific ELISA. Preincubation of non-20-kDaPS-producing clinical strain with increasing amounts of 20-kDaPS inhibits endocytosis by human macrophages, whereas, preincubation of 20-kDaPS-producing strain ATCC35983 with 20-kDaPS antiserum enhances bacterial endocytosis by human macrophages.

Conclusions

In conclusion, icaADBC is not involved in 20-kDaPS synthesis, while the chemical and chromatographic properties of PIA and 20-kDaPS are distinct. 20-kDaPS exhibits anti-phagocytic properties, whereas, 20-kDaPS antiserum may have a beneficial effect on combating infection by 20-kDaPS-producing S. epidermidis.
Computational identification and experimental validation of microRNAs binding to the Alzheimer-related gene ADAM10
Authors: Augustin Regina , Endres Kristina , Reinhardt Sven , Kuhn Peer-Hendrik , Lichtenthaler Stefan F , Hansen Jens , Wurst Wolfgang , Trümbach Dietrich
Published: May 2012

Background

MicroRNAs (miRNAs) are post-transcriptional regulators involved in numerous biological processes including the pathogenesis of Alzheimer’s disease (AD). A key gene of AD, ADAM10, controls the proteolytic processing of APP and the formation of the amyloid plaques and is known to be regulated by miRNA in hepatic cancer cell lines. To predict miRNAs regulating ADAM10 expression concerning AD, we developed a computational approach.

Methods

MiRNA binding sites in the human ADAM10 3' untranslated region were predicted using the RNA22, RNAhybrid and miRanda programs and ranked by specific selection criteria with respect to AD such as differential regulation in AD patients and tissue-specific expression. Furthermore, target genes of miR-103, miR-107 and miR-1306 were derived from six publicly available miRNA target site prediction databases. Only target genes predicted in at least four out of six databases in the case of miR-103 and miR-107 were compared to genes listed in the AlzGene database including genes possibly involved in AD. In addition, the target genes were used for Gene Ontology analysis and literature mining. Finally, we used a luciferase assay to verify the potential effect of these three miRNAs on ADAM10 3'UTR in SH-SY5Y cells.

Results

Eleven miRNAs were selected, which have evolutionary conserved binding sites. Three of them (miR-103, miR-107, miR-1306) were further analysed as they are linked to AD and most strictly conserved between different species. Predicted target genes of miR-103 (p-value = 0.0065) and miR-107 (p-value = 0.0009) showed significant overlap with the AlzGene database except for miR-1306. Interactions between miR-103 and miR-107 to genes were revealed playing a role in processes leading to AD. ADAM10 expression in the reporter assay was reduced by miR-1306 (28%), miR-103 (45%) and miR-107 (52%).

Conclusions

Our approach shows the requirement of incorporating specific, disease-associated selection criteria into the prediction process to reduce the amount of false positive predictions. In summary, our method identified three miRNAs strongly suggested to be involved in AD, which possibly regulate ADAM10 expression and hence offer possibilities for the development of therapeutic treatments of AD.
A vacuum-sealed miniature X-ray tube based on carbon nanotube field emitters
Authors: Heo Sung Hwan , Kim Hyun Jin , Ha Jun Mok , Cho Sung Oh
Published: May 2012

A vacuum-sealed miniature X-ray tube based on a carbon nanotube field-emission electron source has been demonstrated. The diameter of the X-ray tube is 10 mm; the total length of the tube is 50 mm, and no external vacuum pump is required for the operation. The maximum tube voltage reaches up to 70 kV, and the X-ray tube generates intense X-rays with the air kerma strength of 108 Gy·cm2 min−1. In addition, X-rays produced from the miniature X-ray tube have a comparatively uniform spatial dose distribution.
Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility
Authors: Ji Guixiang , Long Yan , Zhou Yong , Huang Cong , Gu Aihua , Wang Xinru
Published: May 2012

Background

The mismatch repair (MMR) pathway plays an important role in the maintenance of the genome integrity, meiotic recombination and gametogenesis. This study investigated whether genetic variations in MMR genes are associated with an increased risk of sperm DNA damage and male infertility.

Methods

We selected and genotyped 21 tagging single nucleotide polymorphisms (SNPs) in five MMR genes (MLH1, MLH3, PMS2, MSH4andMSH5) using the SNPstream 12-plex platform in a case-control study of 1,292 idiopathic infertility patients and 480 fertile controls in a Chinese population. Sperm DNA damage levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay in 450 cases. Fluorescence resonance energy transfer (FRET) and co-immunoprecipitation techniques were employed to determine the effects of functional variants.

Results

One intronic SNP inMLH1(rs4647269) and two non-synonymous SNPs inPMS2(rs1059060, Ser775Asn) andMSH5(rs2075789, Pro29Ser) seem to be risk factors for the development of azoospermia or oligozoospermia. Meanwhile, we also identified a possible contribution ofPMS2rs1059060 to the risk of male infertility with normal sperm count. Among patients with normal sperm count,MLH1rs4647269 andPMS2rs1059060 were associated with increased sperm DNA damage. Functional analysis revealed that thePMS2rs1059060 can affect the interactions between MLH1 and PMS2.

Conclusions

Our results provide evidence supporting the involvement of genetic polymorphisms in MMR genes in the aetiology of male infertility.
Association between a genetic variant in the serotonin transporter gene (SLC6A4) and suicidal behavior in patients with schizophrenia
Authors: Lindholm Carlström Eva , Saetre Peter , Rosengren Anders , Thygesen Johan H , Djurovic Srdjan , Melle Ingrid , Andreassen Ole A , Werge Thomas , Agartz Ingrid , Hall Håkan , Terenius Lars , Jönsson Erik G
Published: May 2012

Background

The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated with schizophrenia and suicidal behavior. In this study, we wanted to elucidate whether SLC6A4 variations is involved in attempted suicide among patients with schizophrenia in a Scandinavian case–control sample.

Methods

Patients diagnosed with schizophrenia from three Scandinavian samples were assessed for presence or absence of suicide attempts, based on record reviews and interview data. Seven SLC6A4 single nucleotide polymorphisms (SNPs) were genotyped in 837 schizophrenia patients and 1,473 control individuals. Association analyses and statistical evaluations were performed with the program UNPHASED (version 3.0.9).

Results

We observed an allele association between the SNP rs16965628, located in intron one of SLC6A4, and attempted suicide (adjusted p-value 0.01), among patients with schizophrenia. No association was found to a diagnosis of schizophrenia, when patients were compared to healthy control individuals.

Conclusion

The gene SLC6A4 appears to be involved in suicidal ideation among patients with schizophrenia. Independent replication is needed before more firm conclusions can be drawn.
Thermotherapy. An alternative for the treatment of American cutaneous leishmaniasis.
Authors: López Liliana , Robayo Martha , Vargas Margarita , Vélez Iván D
Published: May 2012

Background

Pentavalent antimonials (Sb5) and miltefosine are the first-line drugs for treating cutaneous leishmaniasis in Colombia; however, toxicity and treatment duration negatively impact compliance and cost, justifying an active search for better therapeutic options. We compared the efficacy and safety of thermotherapy and m eglumine antimoniate for the treatment of cutaneous leishmaniasis in Colombia.

Method

An open randomized Phase III clinical trial was performed in five military health centres. located in northwestern, central and southern Colombia. Volunteers with parasitological positive diagnosis (Giemsa-stained smears) of cutaneous leishmaniasis were included. A single thermotherapy session involving the application of 50°C at the center and active edge of each lesion. Meglumine antimoniate was administered intramuscularly at a dose of 20 mg Sb5/kg weight/day for 20 days.

Results

Both groups were comparable. The efficacy of thermotherapy was 64% (86/134 patients) by protocol and 58% (86/149) by intention-to-treat. For the m eglumine antimoniate group, efficacy by protocol was 85% (103/121 patients) and 72% (103/143) by intention-to-treat, The efficacy between the treatments was statistically significant (p 0.01 and <0.001) for analysis by intention to treat and by protocol, respectively. There was no difference between the therapeutic response with either treatment regardless of the Leishmania species responsible for infection. The side effects of m eglumine antimoniate included myalgia, arthralgia, headache and fever. Regarding thermotherapy, the only side effect was pain at the lesion area four days after the initiation of treatment.

Conclusion

Although the efficacy rate of m eglumine antimoniate was greater than that of thermotherapy for the treatment of cutaneous leishmaniasis, the side effects were also greater. Those factors, added to the increased costs, the treatment adherence problems and the progressive lack of therapeutic response, make us consider thermotherapy as a first line treatment for cutaneous leishmaniasis. Registered ClinicalTrials.gov NCT00471705
Identification of stable endogenous control genes for transcriptional profiling of photon, proton and carbon-ion irradiated cells
Authors: Sharungbam Geeta D , Schwager Christian , Chiblak Sara , Brons Stephan , Hlatky Lynn , Haberer Thomas , Debus Jürgen , Abdollahi Amir
Published: May 2012

Background

Quantitative analysis of transcriptional regulation of genes is a prerequisite for a better understanding of the molecular mechanisms of action of different radiation qualities such as photon, proton or carbon ion irradiation. Microarrays and real-time quantitative RT-PCR (qRT-PCR) are considered the two cornerstones of gene expression analysis. In interpreting these results it is critical to normalize the expression levels of the target genes by that of appropriately selected endogenous control genes (ECGs) or housekeeping genes. We sought to systematically investigate common ECG candidates for their stability after different radiation modalities in different human cell lines by qRT-PCR. We aimed to identify the most robust set of ECGs or housekeeping genes for transcriptional analysis in irradiation studies.

Methods

We tested the expression stability of 32 ECGs in three human cancer cell lines. The epidermoid carcinoma cells (A431), the non small cell lung carcinoma cells (A549) and the pancreatic adenocarincoma cells (BxPC3) were irradiated with photon, proton and carbon ions. Expression Heat maps, clustering and statistic algorithms were employed using SUMO software package. The expression stability was evaluated by computing: mean, standard deviation, ANOVA, coefficient of variation and the stability measure (M) given by the geNorm algorithm.

Results

Expression analysis revealed significant cell type specific regulation of 18 out of 32 ECGs (p < 0.05). A549 and A431 cells shared a similar pattern of ECG expression as the function of different radiation qualities as compared to BxPC3. Of note, the ribosomal protein 18S, one of the most frequently used ECG, was differentially regulated as the function of different radiation qualities (p ≤ 0.01). A comprehensive search for the most stable ECGs using the geNorm algorithm identified 3 ECGs for A431 and BxPC3 to be sufficient for normalization. In contrast, 6 ECGs were required to properly normalize expression data in the more variable A549 cells. Considering both variables tested, i.e. cell type and radiation qualities, 5 genes-- RPLP0, UBC, PPIA, TBP and PSMC4-- were identified as the consensus set of stable ECGs.

Conclusions

Caution is warranted when selecting the internal control gene for the qRT-PCR gene expression studies. Here, we provide a template of stable ECGs for investigation of radiation induced gene expression.
Factors that influence survival in a probable Alzheimer disease cohort
Authors: Rountree Susan D , Chan Wenyaw , Pavlik Valory N , Darby Eveleen J , Doody Rachelle S
Published: May 2012

Introduction

This longitudinal study examined multiple factors that influence survival in a cohort of Alzheimer patients followed over two decades.

Methods

Time to death after symptom onset was determined in 641 probable AD patients who were evaluated annually until death or loss to follow-up, and information was entered into a longitudinal database. Date of death was available for everyone including those eventually lost. Baseline variables included age, sex, race, disease severity, a calculated index of rate of initial cognitive decline from symptom onset to cohort entry (pre-progression rate or PPR), years of education, and medical comorbidities (diabetes, hypertension, hyperlipidemia, coronary disease, cerebrovascular disease). Multivariable Cox proportional hazard regression analysis was used to analyze the baseline and/or time dependent association in Mini-mental Status Exam (MMSE) severity, Physical Self Maintenance Scale (PSMS), Persistency Index (PI) of exposure to antipsychotic and antidementia drugs, and psychotic symptoms (hallucinations, delusions) with mortality.

Results

Baseline covariates significantly associated with increased survival were younger age (p = .0016), female sex (p = .0001), and a slower PPR (p < .0001). Overall disease severity at baseline, medical comorbidities, and education did not influence time to death. Time-dependent changes in antipsychotic drug use, development of psychotic symptoms, antidementia drug use, and observed MMSE change were not predictive. In the final model the only time-dependent covariate that significantly decreased survival was worsening of functional ability on the PSMS (hazard ratio = 1.10; CI: 1.07-1.11).

Conclusions

In this large AD cohort survival is influenced by age, sex, and the development of functional disability during follow-up. The most important predictor of mortality was a faster rate of cognitive decline at the initial patient visit (PPR). The currently available antidementia drugs do not prolong survival in Alzheimer patients.
T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles
Authors: Law Soi Cheng , Street Shayna , Yu Chien-Hsiung Alan , Capini Christelle , Ramnoruth Sakoontalla , Nel Hendrik J , van Gorp Eline , Hyde Claire , Lau Kim , Pahau Helen , Purcell Anthony W , Thomas Ranjeny
Published: May 2012

Introduction

Anti-citrullinated peptide antibodies are found in rheumatoid arthritis (RA) patients with HLA-DRβ chains encoding the shared epitope (SE) sequence. Citrullination increases self-antigen immunogenicity, through increased binding affinity to SE-containing HLA-DR molecules. To characterise T-cell autoreactivity towards citrullinated self-epitopes, we profiled responses of SE+ healthy controls and RA patients to citrullinated and unmodified epitopes of four autoantigens.

Methods

We compared T-cell proliferative and cytokine responses to citrullinated and native type II collagen 1,237 to 1,249, vimentin 66 to 78, aggrecan 84 to 103 and fibrinogen 79 to 91 in six SE+ healthy controls and in 21 RA patients with varying disease duration. Cytokine-producing cells were stained after incubation with peptide in the presence of Brefeldin-A.

Results

Although proliferative responses were low, IL-6, IL-17 and TNF were secreted by CD4+ T cells of SE+ RA patients and healthy controls, as well as IFNγ and IL-10 secreted by RA patients, in response to citrullinated peptides. Of the epitopes tested, citrullinated aggrecan was most immunogenic. Patients with early RA were more likely to produce IL-6 in response to no epitope or to citrullinated aggrecan, while patients with longstanding RA were more likely to produce IL-6 to more than one epitope. Cytokine-producing CD4+ T cells included the CD45RO+ and CD45RO- and the CD28+ and CD28- subsets in RA patients.

Conclusion

Proinflammatory cytokines were produced by CD4+ T cells in SE+ individuals in response to citrullinated self-epitopes, of which citrullinated aggrecan was most immunogenic. Our data suggest that the T-cell response to citrullinated self-epitopes matures and diversifies with development of RA.
The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children
Authors: Mankhambo Limangeni A , Banda Daniel L ,   The IPD Study Group, Jeffers Graham , White Sarah A , Balmer Paul , Nkhoma Standwell , Phiri Happy , Molyneux Elizabeth M , Hart C Anthony , Molyneux Malcolm E , Heyderman Robert S , Carrol Enitan D
Published: May 2012

Introduction

Severe sepsis is a disease of the microcirculation, with endothelial dysfunction playing a key role in its pathogenesis and subsequent associated mortality. Angiogenesis in damaged small vessels may ameliorate this dysfunction. The aim of the study was to determine whether the angiogenic factors (vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and angiopoietin-1 (Ang-1) and -2 (Ang-2)) are mortality indicators in Malawian children with severe bacterial infection.

Methods

In 293 children with severe bacterial infection, plasma VEGF, PDGF, FGF, and Ang-1 and Ang-2 were measured on admission; in 50 of the children with meningitis, VEGF, PDGF, and FGF were also measured in the CSF. Healthy controls comprised children from some of the villages of the index cases. Univariable and multivariable logistic regression analyses were performed to develop a prognostic model.

Results

The median age was 2.4 years, and the IQR, 0.7 to 6.0 years. There were 211 children with bacterial meningitis (72%) and 82 (28%) with pneumonia, and 154 (53%) children were HIV infected. Mean VEGF, PDGF, and FGF concentrations were higher in survivors than in nonsurvivors, but only PDGF remained significantly increased in multivariate analysis (P = 0.007). Mean Ang-1 was significantly increased, and Ang-2 was significantly decreased in survivors compared with nonsurvivors (6,000 versus 3,900 pg/ml, P = 0.03; and 7,700 versus 11,900 pg/ml, P = 0.02, respectively). With a logistic regression model and controlling for confounding factors, only female sex (OR, 3.95; 95% CI, 1.33 to 11.76) and low Ang-1 (OR, 0.23; 95% CI, 0.08 to 0.69) were significantly associated with mortality. In children with bacterial meningitis, mean CSF VEGF, PDGF, and FGF concentrations were higher than paired plasma concentrations, and mean CSF, VEGF, and FGF concentrations were higher in nonsurvivors than in survivors (P = 0.02 and 0.001, respectively).

Conclusions

Lower plasma VEGF, PDGF, FGF, and Ang-1 concentrations and higher Ang-2 concentrations are associated with an unfavorable outcome in children with severe bacterial infection. These angiogenic factors may be important in the endothelial dysregulation seen in severe bacterial infection, and they could be used as biomarkers for the early identification of patients at risk of a poor outcome.
Surgical intensive care unit clinician estimates of the adequacy of communication regarding patient prognosis
Authors: Aslakson Rebecca A , Wyskiel Rhonda , Shaeffer Dauryne , Zyra Marylou , Ahuja Nita , Nelson Judith E , Pronovost Peter J
Published: May 2012

Introduction

Intensive care unit (ICU) patients and family members repeatedly note accurate and timely communication from health care providers to be crucial to high-quality ICU care. Practice guidelines recommend improving communication. However, few data, particularly in surgical ICUs, exist on health care provider opinions regarding whether communication is effective.

Methods

To evaluate ICU clinician perceptions regarding adequacy of communication regarding prognosis, we developed a survey and administered it to a cross section of surgical ICU nurses, surgical ICU physicians, nurse practitioners (NPs), and surgeons.

Results

Surgeons had a high satisfaction with communication regarding prognosis for themselves (90%), ICU nurses (85%), and ICU physicians and NPs (85%). ICU nurses noted high satisfaction with personal (82%) and ICU physician and NP (71%) communication, but low (2%) satisfaction with that provided by surgeons. ICU physicians and NPs noted high satisfaction with personal (74%) and ICU nurse (88%) communication, but lower (23%) satisfaction with that provided by surgeons. ICU nurses were the most likely (75%) to report speaking to patients and patient families regarding prognosis, followed by surgeons (40%), and then ICU physicians and NPs (33%). Surgeons noted many opportunities to speak to ICU nurses and ICU physicians and NPs about patient prognosis and noted that comments were often valued. ICU physicians and NPs and ICU nurses noted many opportunities to speak to each other but fewer opportunities to communicate with surgeons. ICU physicians and NPs thought that their comments were valued by ICU nurses but less valued by surgeons. ICU nurses thought that their comments were less valued by ICU physicians and NPs and surgeons.

Conclusions

ICU nurses, surgeons, and ICU intensivists and NPs varied widely in their satisfaction with communication relating to prognosis. Clinician groups also varied in whether they thought that they had opportunities to communicate prognosis and whether their concerns were valued by other provider groups. These results hint at the nuanced and complicated relationships present in surgical ICUs. Further validation studies and further evaluations of patient and family member perspectives are needed.
Genome-wide patterns of carbon and nitrogen regulation of gene expression validate the combined carbon and nitrogen (CN)-signaling hypothesis in plants
Authors: Palenchar Peter M , Kouranov Andrei , Lejay Laurence V , Coruzzi Gloria M
Published: May 2012

Background

Carbon and nitrogen are two signals that influence plant growth and development. It is known that carbon- and nitrogen-signaling pathways influence one another to affect gene expression, but little is known about which genes are regulated by interactions between carbon and nitrogen signaling or the mechanisms by which the different pathways interact.

Results

Microarray analysis was used to study global changes in mRNA levels due to carbon and nitrogen in Arabidopsis thaliana. An informatic analysis using InterAct Class enabled us to classify genes on the basis of their responses to carbon or nitrogen treatments. This analysis provides in vivo evidence supporting the hypothesis that plants have a carbon/nitrogen (CN)-sensing/regulatory mechanism, as we have identified over 300 genes whose response to combined CN treatment is different from that expected from expression values due to carbon and nitrogen treatments separately. Metabolism, energy and protein synthesis were found to be significantly affected by interactions between carbon and nitrogen signaling. Identified putative cis-acting regulatory elements involved in mediating CN-responsive gene expression suggest multiple mechanisms for CN responsiveness. One mechanism invokes the existence of a single CN-responsive cis element, while another invokes the existence of cis elements that promote nitrogen-responsive gene expression only when present in combination with a carbon-responsive cis element.

Conclusion

This study has allowed us to identify genes and processes regulated by interactions between carbon and nitrogen signaling and take a first step in uncovering how carbon- and nitrogen-signaling pathways interact to regulate transcription.