bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary Polyunsaturated Fatty Acids Increase Survival and Decrease Bacterial Load during Septic Staphylococcus aureus Infection and Improve Neutrophil Function in Mice
Authors: Svahn Sara L. , Grahnemo Louise , Pálsdóttir Vilborg , Nookaew Intawat , Wendt Karl , Gabrielsson Britt , Schéle Erik , Benrick Anna , Andersson Niklas , Nilsson Staffan , Johansson Maria E. , Jansson John-Olov 
Published: November 2014

ABSTRACT

Severe infection, including sepsis, is an increasing clinical problem that causes prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of resistance to antibiotics is increasing; therefore, it is critical to find new therapies for sepsis.
Staphylococcus aureus
is a major cause of septic mortality. Neutrophils play an important role in the defense against bacterial infections. We have shown that a diet with high levels of dietary saturated fatty acids decreases survival in septic mice, but the mechanisms behind this remain elusive. The aim of the present study was to investigate how the differences in dietary fat composition affect survival and bacterial load after experimental septic infection and neutrophil function in uninfected mice. We found that, after
S. aureus
infection, mice fed a polyunsaturated high-fat diet (HFD-P) for 8 weeks had increased survival and decreased bacterial load during sepsis compared with mice fed a saturated high-fat diet (HFD-S), similar to mice fed a low-fat diet (LFD). Uninfected mice fed HFD-P had a higher frequency of neutrophils in bone marrow than mice fed HFD-S. In addition, mice fed HFD-P had a higher frequency of neutrophils recruited to the site of inflammation in response to peritoneal injection of thioglycolate than mice fed HFD-S. Differences between the proportion of dietary protein and carbohydrate did not affect septic survival at all. In conclusion, polyunsaturated dietary fat increased both survival and efficiency of bacterial clearance during septic
S. aureus
infection. Moreover, this diet increased the frequency and chemotaxis of neutrophils, key components of the immune response to
S. aureus
infections.
Transcriptional Profiling of Human Epithelial Cells Infected with Plasmid-Bearing and Plasmid-Deficient Chlamydia trachomatis
Authors: Porcella Stephen F. , Carlson John H. , Sturdevant Daniel E. , Sturdevant Gail L. , Kanakabandi Kishore , Virtaneva Kimmo , Wilder Hannah , Whitmire William M. , Song Lihua , Caldwell Harlan D. 
Published: November 2014

ABSTRACTChlamydia trachomatisis an obligate intracellular epitheliotropic bacterial pathogen of humans. Infection of the eye can result in trachoma, the leading cause of preventable blindness in the world. The pathophysiology of blinding trachoma is driven by multiple episodes of reinfection of conjunctival epithelial cells, producing an intense chronic inflammatory response resulting in submucosal tissue remodeling and scarring. Recent reports have shown that infection with trachoma organisms lacking the cryptic chlamydial plasmid is highly attenuated in macaque eyes, a relevant experimental model of human trachoma infection. To better understand the molecular basis of plasmid-mediated infection attenuation and the potential modulation of host immunity, we conducted transcriptional profiling of human epithelial cells infected withC. trachomatisplasmid-bearing (A2497) and plasmid-deficient (A2497P−) organisms. Infection of human epithelial cells with either strain increased the expression of host genes coding for proinflammatory (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage colony-stimulating factor [MCSF], interleukin-6 [IL-6], IL-8, IL-1α, CXCL1, CXCL2, CXCL3, intercellular adhesion molecule 1 [ICAM1]), chemoattraction (CCL20, CCL5, CXCL10), immune suppression (PD-L1, NFKB1B, TNFAIP3, CGB), apoptosis (CASP9, FAS, IL-24), and cell growth and fibrosis (EGR1 and IL-20) proteins. Statistically significant increases in the levels of expression of many of these genes were found in A2497-infected cells compared to the levels of expression in A2497P−-infected cells. Our findings suggest that the chlamydial plasmid plays a focal role in the host cell inflammatory response to infection and immune avoidance. These results provide new insights into the role of the chlamydial plasmid as a chlamydial virulence factor and its contributions to trachoma pathogenesis.
Pleiotropic Effects of Cell Wall Amidase LytA on Streptococcus pneumoniae Sensitivity to the Host Immune Response
Authors: Ramos-Sevillano Elisa , Urzainqui Ana , Campuzano Susana , Moscoso Miriam , González-Camacho Fernando , Domenech Mirian , Rodríguez de Córdoba Santiago , Sánchez-Madrid Francisco , Brown Jeremy S. , García Ernesto , Yuste Jose 
Published: November 2014

ABSTRACT

The complement system is a key component of the host immune response for the recognition and clearance of
Streptococcus pneumoniae
. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to
S. pneumoniae
, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the
lytA ply
double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.
Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate
Authors: Zahir Hamim , Brown Karen S. , Vandell Alexander G. , Desai Madhuri , Maa Jen-Fue , Dishy Victor , Lomeli Barbara , Feussner Annette , Feng Wenqin , He Ling , Grosso Michael A. , Lanz Hans J. , Antman Elliott M. 
Published: November 2014

Background—
The oral factor Xa inhibitor edoxaban has demonstrated safety and efficacy in stroke prevention in patients with atrial fibrillation and in the treatment and secondary prevention of venous thromboembolism. This study investigated the reversal of edoxaban’s effects on bleeding measures and biomarkers by using a 4-factor prothrombin complex concentrate (4F-PCC).

Methods and Results—
This was a phase 1 study conducted at a single site. This was a double-blind, randomized, placebo-controlled, 2-way crossover study to determine the reversal effect of descending doses of 4F-PCC on bleeding duration and bleeding volume following edoxaban treatment. A total of 110 subjects (17 in part 1, 93 in part 2) were treated. Intravenous administration of 4F-PCC 50, 25, or 10 IU/kg following administration of edoxaban (60 mg) dose-dependently reversed edoxaban’s effects on bleeding duration and endogenous thrombin potential, with complete reversal at 50 IU/kg. Effects on prothrombin time were partially reversed at 50 IU/kg. A similar trend was seen for bleeding volume.

Conclusions—
The 4F-PCC dose-dependently reversed the effects of edoxaban (60 mg), with complete reversal of bleeding duration and endogenous thrombin potential and partial reversal of prothrombin time following 50 IU/kg. Edoxaban alone and in combination with 4F-PCC was safe and well tolerated in these healthy subjects. A dose of 50 IU/kg 4F-PCC may be suitable for reversing edoxaban anticoagulation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02047565.
The development of the Pediatric Motivation Scale for rehabilitation
Authors: Tatla Sandy K. , Jarus Tal , Virji-Babul Naznin , Holsti Liisa 
Published: November 2014

Background. Clinicians recognize that client motivation is key to optimizing rehabilitation; however, they are limited in its assessment by a paucity of motivation measures. Purpose. This paper presents the preliminary psychometrics of the Pediatric Motivation Scale (PMOT) designed to measure motivation from a child’s perspective. Method. Content validity of the PMOT was measured through expert feedback ( n = 12), and field testing ocurred with 41 children, 21 in rehabilitation and 20 healthy. Pearson product-moment correlations were used to analyze subscale correlations, test-retest reliability, and convergent validity with the Pediatric Volitional Questionnaire (PVQ). Internal consistency was measured using Cronbach’s alpha. Findings. Preliminary psychometric evaluation indicates strong internal consistency for PMOT total (α = .96) and subscales (α = .79–.91). The PMOT and PVQ moderately correlated in the rehabilitation subsample ( r = .71, p < .01); no correlation was found in the healthy subsample ( p > .05). Test-retest reliability was excellent ( r = .97). Implications. This study provides preliminary psychometric evidence of the PMOT for children undergoing rehabilitation. These pilot findings warrant ongoing scale development.
REBOUND: A media-based life skills and risk education programme
Authors: Kröninger-Jungaberle Henrik , Nagy Ede , von Heyden Maximilian , DuBois Fletcher ,   the REBOUND Participative Development Group, Ullrich Jens , Wippermann Christina , Pospiech Björn , Gordon Vanessa , Haubold Lena , Breitner Stefanie , Lieneweg Sascha , Hochadel Sarah , Brommond Michaela 
Published: November 2014

Background: REBOUND is a novel media-based life skills and risk education programme developed for 14- to 25-year olds in school, university or youth group settings. This paper outlines the programme’s rationale, curriculum and implementation. It provides information of relevance to researchers, programme developers and policymakers. Methods/design of the programme: The programme is based on a form of cooperative learning. It is facilitated by teachers and other professionals and supported by peer mentors. The curriculum is centred around ‘explorative film work’ with short films/videos depicting risk behaviours and life challenges. The methodology aims to promote risk competence and positive norm-building in social groups. The programme consists of a course comprising 16 units, 10 of which focus on psychosocial strength (resilience) and 6 on risks of alcohol and other drugs. Implementation is supported by a mentoring system, a voluntary eLearning component and tools for organisational development. The programme has been evaluated with about 1,000 students in the intervention group of a controlled study using a mixed-method design involving structured stakeholder and peer feedback. Discussion: REBOUND is one of the few health promotion/prevention programmes to have been entirely developed together with those (students, facilitators, school administrators) for whom the programme is intended.
Inhibitory CD200R and proapoptotic CD95/CD95L molecules on innate immunity cells are modulated by cardiac surgery
Authors: Holmannova D , Kolackova M , Mandak J , Kunes P , Holubcova Z , Krejsek J , Vlaskova D , Andrys C 
Published: November 2014

Introduction: Cardiac surgery directly initiates a systemic inflammatory response with the activation of both cellular and humoral parts of the immune system. Exaggerated immune system activation is associated with a risk of life-threatening multi-organ dysfunction (MOD) and increased morbidity and mortality in the postoperative period. The immune system response is regulated and terminated by inhibitory mechanisms, including the regulatory membrane molecules, such as CD200R, CD95, CD95L and soluble sCD200R. Methods: We measured the expression of CD95, CD95L, CD200R and sCD200R molecules in granulocyte and monocyte populations in blood samples of 30 patients who underwent coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). Samples collected before surgery, after surgery and in the postoperative period were analyzed by flow cytometry and ELISA. Results: We found a significant increase in the percentage of granulocytes featuring the anti-inflammatory molecule CD200R (from 5% to 17.8%) after surgery. We presume that these cells were less susceptible to apoptosis because they rarely expressed CD95 as the CD200R+CD95– granulocyte sub-population prevailed. Only a small percentage of CD200R+ granulocytes expressed simultaneously CD95 (from 0.5 to 2.06 %). This small population of CD200R+CD95+ cells decreased expression of CD200R after surgery and, thus, was likely to be a source of increased sCD200R in serum (from 96 to 294 ng/mL). Also, the expression of CD95L on CD200R+ granulocytes and CD95 on CD200R+ monocytes was affected by surgery. The percentage of CD200R+ monocytes was elevated on the 1st postoperative day (from 30.6 to 49.4 %) and dropped below the preoperative value on the 7th day after surgery (from 30.6 to 19.8 %). This population comprised mainly CD200R+CD95+ monocytes in which the enhanced expression of CD95 was found. Conclusion: Our data show that the expression of CD200R, CD95 and CD95L was influenced by cardiac surgery and imply the role of these membrane molecules in cell regulation–inhibition and apoptosis following cardiac surgery.
A randomized controlled trial in non-responders from Newcastle upon Tyne invited to return a self-sample for Human Papillomavirus testing versus repeat invitation for cervical screening
Authors: Cadman Louise , Wilkes Scott , Mansour Diana , Austin Janet , Ashdown-Barr Lesley , Edwards Rob , Kleeman Michelle , Szarewski Anne 
Published: November 2014

Background Non-attenders for cervical screening are at increased risk of cervical cancer. Studies offering self-sampling for high-risk Human Papillomavirus (HrHPV) testing have shown greater uptake than sending another invitation for cytology. Objectives To explore whether uptake would increase in a less diverse, more stable population than the previous English study, which demonstrated a lower response rate than other studies. The primary objective was whether non-attenders were more likely to respond to a postal invitation, including kit, to collect a self-sample compared with a further invitation for cytology screening. The secondary objective was whether women with an abnormal result would attend for follow-up. Methods 6000 non-attenders for screening in this pragmatic, randomized (1:1) controlled trial in Newcastle-upon-Tyne were sent an HPV self-sample kit (intervention) or a further invitation for cytology screening (comparator). Results 411(13%) responded to the intervention, returning a self-sample (247(8%)) or attending for cytology (164(5%)), compared with 183(6%) attending for cytology, relative risk 2.25 (95% CI 1.90–2.65) (comparator arm). Of those testing hrHPV positive (32(13%)), 19(59%) subsequently attended cytology screening. Of those in the intervention group who attended for cytology screening without returning an hrHPV self-sample (n = 164), 5% (n = 8) were referred for colposcopy - all attended. In the comparator group eight of the nine referred for colposcopy attended. Conclusion Persistent non-responders to invitations for cervical screening are significantly more likely to respond to a postal invitation to return a self-collected sample for HPV testing than a further invitation for cytology screening. However, just over half followed up on this positive HPV result.
Deconstructing Engagement
Authors: Whitton Nicola , Moseley Alex 
Published: November 2014

Background. The discourse of learner engagement has become prevalent in formal education research and practice in recent years. However, the term has multiple meanings and various constructions, particularly in the context of games and learning, where the coming together of two different disciplinary constructs creates ambiguity and tensions. Aim. The notions of engagement with education and engagement with games are not necessarily mutually compatible, and this article aims to explore this. Method. This article starts by exploring the use of the term by deconstructing the idea of engagement, and highlighting issues with the way in which people use it in different contexts. Next, it discusses practical and theoretical limitations of the concept, such as the assumed link between engagement and learning and measurement of engagement. Results. The core contribution of the article is a synthesis of the complex literature in this field presented as a model of engagement with learning based on six ways of constructing engagement: participation, attention, captivation, passion, affiliation, and incorporation. Conclusion. The article concludes by discussing the benefits and possible uses of this model, and highlighting necessary further research to forward the field of games and learning in this area.
Correlation Between Static Radiographic Measurements and Intersegmental Angular Measurements During Gait Using a Multisegment Foot Model
Authors: Lee Dong Yeon , Seo Sang Gyo , Kim Eo Jin , Kim Sung Ju , Lee Kyoung Min , Farber Daniel C. , Chung Chin Youb , Choi In Ho 
Published: November 2014

Background: Radiographic examination is a widely used evaluation method in the orthopedic clinic. However, conventional radiography alone does not reflect the dynamic changes between foot and ankle segments during gait. Multiple 3-dimensional multisegment foot models (3D MFMs) have been introduced to evaluate intersegmental motion of the foot. In this study, we evaluated the correlation between static radiographic indices and intersegmental foot motion indices. Methods: One hundred twenty-five females were tested. Static radiographs of full-leg and anteroposterior (AP) and lateral foot views were performed. For hindfoot evaluation, we measured the AP tibiotalar angle (TiTA), talar tilt (TT), calcaneal pitch, lateral tibiocalcaneal angle, and lateral talcocalcaneal angle. For the midfoot segment, naviculocuboid overlap and talonavicular coverage angle were calculated. AP and lateral talo-first metatarsal angles and metatarsal stacking angle (MSA) were measured to assess the forefoot. Hallux valgus angle (HVA) and hallux interphalangeal angle were measured. In gait analysis by 3D MFM, intersegmental angle (ISA) measurements of each segment (hallux, forefoot, hindfoot, arch) were recorded. Results: ISAs at midstance phase were most highly correlated with radiography. Significant correlations were observed between ISA measurements using MFM and static radiographic measurements in the same segment. In the hindfoot, coronal plane ISA was correlated with AP TiTA ( P < .001) and TT ( P = .018). In the hallux, HVA was strongly correlated with transverse ISA of the hallux ( P < .001). Conclusion: The segmental foot motion indices at midstance phase during gait measured by 3D MFM gait analysis were correlated with the conventional radiographic indices. Clinical Relevance: The observed correlation between MFM measurements at midstance phase during gait and static radiographic measurements supports the fundamental basis for the use of MFM in analysis of dynamic motion of foot segment during gait.
A rare cause of acute pancreatitis: Percutaneous mechanical rheolytic thrombectomy of deep venous thrombosis
Authors: Dass Param , Robertson Jason , Muthu Carl , Holden Andrew 
Published: November 2014

Introduction Percutaneous mechanical rheolytic thrombectomy is an effective treatment option for deep vein thrombosis as well as arterial and graft thromboses. Acute pancreatitis, a rare complication of this technique, is described in this case report. Case report A 40-year-old man underwent AngioJet mechanical rheolytic thrombectomy for iliocaval deep vein thrombosis. He subsequently developed acute pancreatitis. This case report outlines the clinical presentation of acute pancreatitis after rheolytic thrombectomy and also discusses the possible pathogenesis and etiological factors.
HDAC and HAT Inhibitors Differently Affect Analgesia Mediated by Group II Metabotropic Glutamate Receptors
Authors: Zammataro Magda , Sortino Maria Angela , Parenti Carmela , Gereau Robert W , Chiechio Santina 
Published: November 2014

Background: Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are key players in epigenetic regulation of gene expression. Analgesic activity by HDAC inhibitors has been reported in different pain models including inflammatory and neuropathic pain. These drugs interfere with gene expression through different mechanisms including chromatin remodeling and/or activation of transcription factors. Among other targets, HDAC inhibitors regulate metabotropic glutamate receptors type 2 (mGlu2) expression in central and peripheral central nervous system. However whether inhibition of HAT activity also regulates mGlu2 expression has not been reported. Findings: Here we report that curcumin (CUR), a naturally occurring compound endowed with p300/CREB-binding protein HAT inhibitory activity, is able to induce a drastic down-regulation of the mGlu2 receptor in the mouse spinal cord after systemic administration together with a marked hypoacetylation of histones H3 and H4 in dorsal root ganglia (DRG). Furthermore, the analgesic activity of the mGlu2/3 agonist, LY379268 is lost after a 3-day treatment with CUR. Conversely the analgesic activity of LY379268 is potentiated in mice pretreated for 5 consecutive days with the HDAC inhibitor, Suberoylanilide Hydroxamic Acid (SAHA), known to induce mGlu2-upregulation. Conclusions: Our results demonstrate that systemically injected CUR is able to inhibit H3 and H4 acetylation in the DRG and to down-regulate mGlu2 receptors in the spinal cord. We also demonstrate that long term modification of the mGlu2 expression affects the analgesic properties of the orthosteric mGlu2/3 agonist, LY379268. These data open up the possibility that epigenetic modulators might be given in combination with “traditional” drugs in a context of a multi target approach for a better analgesic efficacy.
HAV in fresh vegetables: a hidden health risk in district Mardan, Pakistan
Authors: Khan Waleed , Irshad Muhammad , Rehman Gauhar , Hussain Anwar 
Published: November 2014

Abstract
Hepatitis A is an acute inflammation of the liver caused by the hepatitis A virus (HAV) in human. The path of entry of HAV to the bloodstream is the epithelium of the intestine. Liver inflammation occurs when HAV multiplies within the hepatocytes and Kupffer cells of the liver. HAV is mostly transmitted by contaminated water, fruits and vegetables. The purpose of the current study was to evaluate fresh vegetables raised on the fecal contaminated water for the detection of HAV by PCR method. Twenty nine samples were collected from 13 different locations of district Mardan and screened for the presence of HAV. Village Bajowro near Takht Bhai was the most contaminated site having HAV in all vegetables grown over there. Water samples collected from this area proved to be contaminated with HAV. It may be concluded that fecal contaminated water is unsafe for irrigation because of the health risk associated with such practices.