bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission
Authors: Tutterrow Yeung L. , Avril Marion , Singh Kavita , Long Carole A. , Leke Robert J. , Sama Grace , Salanti Ali , Smith Joseph D. , Leke Rose G. F. , Taylor Diane W. 
Published: February 2012

ABSTRACT

Placental malaria, caused by sequestration of
Plasmodium falciparum
-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity.
The CovS/CovR Acid Response Regulator Is Required for Intracellular Survival of Group B Streptococcus in Macrophages
Authors: Cumley Nicola J. , Smith Leanne M. , Anthony Mark , May Robin C. 
Published: February 2012

ABSTRACT

Group B
Streptococcus
(GBS) is a leading cause of neonatal meningitis and septicemia. The ability of this organism to survive inside phagocytic cells is poorly understood but thought to be an important step for the establishment of disease in the host. Here, we demonstrate that GBS shows prolonged survival within J774 macrophages and that the capacity to survive is not significantly changed across a diverse range of strains representing different serotypes, multilocus sequence types (MLST), and sites of clinical isolation. Using staining for the lysosome-associated membrane protein (LAMP) and by pharmacological inhibition of phagosome acidification, we demonstrate that streptococci reside in a phagosome and that acidification of the phagosome is required for GBS to survive intracellularly. Moreover, we show that the GBS two-component system CovS/CovR, which is the major acid response regulator in this organism, is required for survival inside the phagosome.
Leptin Protects Host Cells from Entamoeba histolytica Cytotoxicity by a STAT3-Dependent Mechanism
Authors: Marie Chelsea S. , Verkerke Hans P. , Paul Shom N. , Mackey Aaron J. , Petri William A. 
Published: February 2012

ABSTRACTThe adipocytokine leptin links nutritional status to immune function. Leptin signaling protects from amebiasis, but the molecular mechanism is not understood. We developed anin vitromodel of ameba-host cell interaction to test the hypothesis that leptin prevents ameba-induced apoptosis in host epithelial cells. We demonstrated that activation of mammalian leptin signaling increased cellular resistance to amebic cytotoxicity, including caspase-3 activation. Exogenous expression of the leptin receptor conferred resistance in susceptible cells, and leptin stimulation enhanced protection. A series of leptin receptor signaling mutants showed that resistance to amebic cytotoxicity was dependent on activation of STAT3 but not the Src homology-2 domain-containing tyrosine phosphatase (SHP-2) or STAT5. A common polymorphism in the leptin receptor (Q223R) that increases susceptibility to amebiasis in humans and mice was found to increase susceptibility to amebic cytotoxicity in single cells. The Q223R polymorphism also decreased leptin-dependent STAT3 activation by 21% relative to that of the wild-type (WT) receptor (P= 0.035), consistent with a central role of STAT3 signaling in protection. A subset of genes uniquely regulated by STAT3 in response to leptin was identified. Most notable were the TRIB1 and suppressor of cytokine signaling 3 (SOCS3) genes, which have opposing roles in the regulation of apoptosis. Overall apoptotic genes were highly enriched in this gene set (P< 1E−05), supporting the hypothesis that leptin regulation of host apoptotic genes via STAT3 is responsible for protection. This is the first demonstration of a mammalian signaling pathway that restricts amebic pathogenesis and represents an important advance in our mechanistic understanding of how leptin links nutrition and susceptibility to infection.
Involvement of Peptidylprolyl
cis
/
trans
Isomerases in Enterococcus faecalis Virulence
Authors: Reffuveille Fany , Connil Nathalie , Sanguinetti Maurizio , Posteraro Brunella , Chevalier Sylvie , Auffray Yanick , Rince Alain 
Published: February 2012

ABSTRACT

Peptidylprolyl
cis
/
trans
isomerases (PPIases) are enzymes involved in protein folding. Analysis of the genome sequence of
Enterococcus faecalis
V583 allowed for identification of 3 PPIases carrying genes.
ef2898
encodes an intracellular PPIase which was not shown to be important for the
E. faecalis
stress response or virulence. The other two PPIases, the parvulin family rotamase EF0685 and the cyclophilin family member EF1534, are expected to be surface-exposed proteins. They were shown to be important for virulence and resistance to NaCl. A Δ
ef0685
Δ
ef1534
mutant was also more resistant to oxidative stress, was able to grow under a high manganese concentration, and showed altered resistance to ampicillin and quinolone antibiotics.
Effect of specific resistance training on forearm pain and work disability in industrial technicians: cluster randomised controlled trial
Authors: Andersen Lars L , Jakobsen Markus D , Pedersen Mogens T , Mortensen Ole S , Sjøgaard Gisela , Zebis Mette K 
Published: February 2012

ObjectivesTo determine the effect of specific resistance training on forearm pain and work disability in industrial technicians.Design and settingTwo-armed cluster randomised controlled trial of 20 weeks performed at two industrial production units in Copenhagen, Denmark.ParticipantsWorking-age industrial technicians both with and without pain and disability.InterventionsThe training group (n=282) performed specific resistance training for the shoulder, neck and arm muscles three times a week. The control group (n=255) was advised to continue normal physical activity.OutcomeAll participants rated forearm pain intensity (Visual Analogue Scale, 0–100 mm) once a week (primary outcome) and replied to a questionnaire on work disability (Disability of the Arm Shoulder and Hand, 0–100) at baseline and follow-up (secondary outcome).ResultsQuestionnaires were sent to 854 workers of which 30 (n=282) and 27 (n=255) clusters were randomised to training and control, respectively. Of these, 211 and 237 participants, respectively, responded to the follow-up questionnaire. Intention-to-treat analyses including both individuals with and without pain showed that from baseline to follow-up, pain intensity and work disability decreased more in the training group than in the control group (4–5 on a scale of 0–100, p<0.01–0.001). Among those with pain >30 mm Visual Analogue Scale at baseline (n=54), the OR for complete recovery at follow-up in the training group compared with the control group was 4.6 (95% CI 1.2 to 17.9). Among those with work disability >30 at baseline (n=113), the OR for complete recovery at follow-up in the training group compared with the control group was 6.0 (95% CI 1.8 to 19.8).ConclusionSpecific resistance training of the shoulder, neck and arm reduces forearm pain and work disability among industrial technicians.Trial registration numberNCT01071980.
Where do patients known to a community palliative care service die?
Authors: Capel Margred , Gazi Terri , Vout Lauren , Wilson Nicola , Finlay Ilora 
Published: February 2012

ObjectivesThe majority of people would prefer to die at home and National Health Service policy aims to support this concept. This service evaluation compared the preferred and actual place of death of patients known to a specialist community palliative care service.DesignAll deaths of patients (n=788) known to the specialist palliative care service from 1 January 2009 to 31 December 2010 were examined in a service evaluation to compare the actual place of death with the preferred place of death previously identified by the patient. Triggers for admission were established when patients did not achieve this preference.Results69% of patients (n=263) who expressed a preference to die at home and 82% of patients (n=93) who expressed a preference to die as inpatients in the hospice fulfilled these preferences. 71% of patients (n=298) who wanted to die in their current place of residence achieved this preference.54% of patients (n=121) who declined to express a preference for end-of-life care subsequently died in hospital, reflecting the importance of advance care planning.ConclusionsThe perceived lack of social support for patients dying at home is a significant trigger for admission to a hospice. The provision of sitters to support patients dying at home may ensure people achieve their preference. Commissioners consider preferred place of care to be a marker of quality, but clinical events that precipitate admission are often outside the influence of the palliative care team.
Development of Prognosis in Palliative care Study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study
Authors: Gwilliam Bridget , Keeley Vaughan , Todd Chris , Gittins Matthew , Roberts Chris , Kelly Laura , Barclay Stephen , Stone Patrick C 
Published: February 2012

ObjectiveTo develop a novel prognostic indicator for use in patients with advanced cancer that is significantly better than clinicians' estimates of survival.DesignProspective multicentre observational cohort study.Setting18 palliative care services in the UK (including hospices, hospital support teams, and community teams).Participants1018 patients with locally advanced or metastatic cancer, no longer being treated for cancer, and recently referred to palliative care services.Main outcome measuresPerformance of a composite model to predict whether patients were likely to survive for “days” (0-13 days), “weeks” (14-55 days), or “months+” (>55 days), compared with actual survival and clinicians' predictions.ResultsOn multivariate analysis, 11 core variables (pulse rate, general health status, mental test score, performance status, presence of anorexia, presence of any site of metastatic disease, presence of liver metastases, C reactive protein, white blood count, platelet count, and urea) independently predicted both two week and two month survival. Four variables had prognostic significance only for two week survival (dyspnoea, dysphagia, bone metastases, and alanine transaminase), and eight variables had prognostic significance only for two month survival (primary breast cancer, male genital cancer, tiredness, loss of weight, lymphocyte count, neutrophil count, alkaline phosphatase, and albumin). Separate prognostic models were created for patients without (PiPS-A) or with (PiPS-B) blood results. The area under the curve for all models varied between 0.79 and 0.86. Absolute agreement between actual survival and PiPS predictions was 57.3% (after correction for over-optimism). The median survival across the PiPS-A categories was 5, 33, and 92 days and survival across PiPS-B categories was 7, 32, and 100.5 days. All models performed as well as, or better than, clinicians' estimates of survival.ConclusionsIn patients with advanced cancer no longer being treated, a combination of clinical and laboratory variables can reliably predict two week and two month survival.
Quality for home palliative care: an Italian metropolitan multicentre JCI-certified model
Authors: Rizzi Franco , Pizzuto Massimo , Lodetti Laura , Corli Oscar , Da Col Daria , Damiani Maria Eugenia , Mihali Dorian , Piva Laura , Saita Luigi , Vinci Maria , Bonaldi Antonio 
Published: February 2012

BackgroundAssessing the quality of care and service delivery through the analysis of ad hoc indicators is a relevant process for quality monitoring and improvement with a view to providing patients, the community and administrators alike with appropriate elements of evaluation. This paper describes the key results of a certification process based on the Joint Commission International (JCI) criteria for the home hospitalisation model implemented by the palliative care units of seven Milan hospitals for terminally ill patients with cancer.MethodsIn 2006, the interhospital working team implemented a certification project based on the JCI Disease or Condition-Specific Care (DSCS) programme. Thirty standards subdivided into five functional areas with 150 measurable elements were the starting-point for periodic improvement plans within and across participating hospitals. Programme compliance was analysed in terms of annual performance improvement and consistency across the seven PCUs involved in achieving set goals. The JCI standards were applied on 3316 terminally ill patients with cancer treated at home from 2005 to 2009.ResultsAs a result of the work carried out, the JCI survey conducted 3 years after project implementation demonstrated full compliance with the established standards, leading to the JCI certification award (for the first time in this clinical setting internationally).ConclusionThe work carried out with a view to certification has confirmed the possibility that facilities spread across different hospitals can actually share common processes and standardise the activities for the care of end-of-life patients with cancer at home as if they were one single service provider.
Malley diabase dykes of the Slave craton, Canadian Shield: U–Pb age, paleomagnetism, and implications for continental reconstructions in the early Paleoproterozoic1Geological Survey of Canada Contribution 20110114.
Authors: Buchan Kenneth L. , LeCheminant Anthony N. , van Breemen Otto 
Published: February 2012

The NE-trending Malley dyke swarm, dated herein at 2231 ± 2 Ma (U–Pb baddeleyite), extends from the central Slave craton to the vicinity of the Kilohigok basin, and may continue farther to the northeast as the geochemically similar Brichta dyke swarm, having been offset sinistrally along the prominent Bathurst fault. It carries a characteristic high unblocking temperature paleomagnetic component of single polarity directed up SE (mean direction: D = 138.3°, I = –53.8°), with corresponding paleopole at 50.8°S, 50.0°W. Lower unblocking temperature components, in some cases directed down SE, similar to ca 1.75 Ga post-Hudsonian overprints, are easily removed using combined alternating field (AF) thermal demagnetization, but difficult to remove using AF cleaning alone. The characteristic remanence has not been demonstrated primary, but is significantly older than 2.03 Ga, the age of Lac de Gras dykes, based on a baked contact test at a Lac de Gras – Malley dyke intersection. In addition, an E- to ESE-trending dyke carries a down WNW remanence, typical of 2.19 Ga Dogrib dykes near Yellowknife, suggesting that regional overprinting has not affected the study area since Dogrib emplacement, and that the Malley remanence was acquired at or shortly after Malley emplacement. Comparing Malley and Lac de Gras paleopoles with the 2.22–2.00 Ga Superior craton apparent polar wander path indicates that the two cratons were (i) not in their present relative orientation at 2.23 or 2.03 Ga, and (ii) likely not drifting in close proximity to one another as parts of a single (super)continent throughout the 2.23–2.03 Ga interval.
Mafic and ultrapotassic rocks from the Canyon domain (central Grenville Province): geochemistry and tectonic implications
Authors: Valverde Cardenas Carolina , Indares Aphrodite , Jenner George 
Published: February 2012

The Canyon domain and the Banded complex in the Manicouagan area of the Grenville Province preserve a record of magmatic activity from ∼1.4 to 1 Ga. This study focuses on 1.4–1.2 Ga mafic rocks and 1 Ga ultrapotassic dykes. Geochemistry and Sm–Nd isotopic signatures were used to constrain the origin of these rocks and evaluate the changing role of the mantle with time and tectonic setting from the late evolution of the Laurentian margin to the Grenvillian orogeny, in the Manicouagan area. The mafic rocks include layers inferred to represent flows, homogeneous bodies in mafic migmatite, and deformed dykes, all of which were recrystallized under granulite-facies conditions during the Grenvillian orogeny. In spite of the complexities inherent in these deformed and metamorphosed mafic rocks, we were able to recognize suites with distinctive geochemical and isotopic signatures. Integration of this data along with available ages is consistent with a 1.4 Ga continental arc cut by 1.2 Ga non-arc basalts derived from depleted asthenospheric mantle, with varied degrees of crustal contamination and inferred to represent magmatism in an extensional environment. The 1 Ga ultrapotassic dykes postdate the Grenvillian metamorphism. They are extremely enriched in incompatible elements, have negative Nb anomalies, relatively unradiogenic Sr-isotopic compositions (initial 87Sr/86Sr ~ 0.7040) and εNd –3 to –15. Some dykes have compositional characteristics consistent with derivation from the mantle, ruling out crustal contamination as a major process in their petrogenesis. The most likely source region for the ultrapotassic dykes is a metasomatized subcontinental lithospheric mantle, with thermal input from the asthenosphere in association with post-orogenic delamination.
Therapeutic efficacy of Hypericum perforatum L. extract for mice infected with an influenza A virus
Authors: Xiuying Pu , Jianping Liang , Ruofeng Shang , Liye Zhou , Xuehong Wang , Yan Li 
Published: February 2012

Hypericum perforatum L., a plant used in Chinese herbal medicine, has been proven effective against many viral diseases. In the present study, the therapeutic efficacy of an extract of H. perforatum (HPE) against influenza A virus (IAV) was investigated in mice. Whether HPE would be a promising agent for influenza treatment was evaluated by measuring the protection rate, mean survival days, lung index, and viral titer, as well as the secretion of IL-6, interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ) in lung tissue and serum on days 3 and 5 post-infection. The results showed that HPE could reduce the lung index and viral titer of mice infected with IAV, decrease mortality, and prolong the mean survival time. HPE decreased the concentration of IL-6 and TNF-α in lung tissue and serum on day 5 post-infection. In contrast, HPE enhanced the lung and serum levels of IL-10 and IFN-γ on the days 3 and 5 post-infection. Our study indicates that HPE has significant therapeutic efficacy for mice infected with IAV. The possible reasons for these results were concluded to be pertaining to up-regulating the expression of IL-10 and IFN-γ, and down-regulating the secretion of IL-6 and TNF-α in lung and serum.
Blood pressure reducing effects ofPhalaris canariensisin normotensive and spontaneously hypertensive rats
Authors: Passos Clévia Santos , Carvalho Lucimeire Nova , Pontes Roberto Braz , Campos Ruy Ribeiro , Ikuta Olinda , Boim Mirian Aparecida 
Published: February 2012

The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHRY, 3 weeks old). Animals received AEPc (400 mg·kg–1·day–1, by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHRYbecame hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHRY, but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na+excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kinurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.
Choice of diet impacts the incidence of stroke-related symptoms in the spontaneously hypertensive stroke-prone rat model
Authors: Slemmer Jennifer E. , Shaughnessy Kevin S. , Scanlan Adam P. , Sweeney Marva I. , Gottschall-Pass Katherine T. 
Published: February 2012

The spontaneously hypertensive stroke-prone (SHRSP) rat is a commonly used model of cerebrovascular disease and hypertension. SHRSP rats have been shown to develop stroke-related symptoms (SRS) by age 14 weeks when fed a purified diet, such as AIN-93G, supplemented with 1% NaCl. We conducted a pathology pilot study to compare the incidence of SRS in SHRSP rats fed either AIN-93G (with 1% NaCl in drinking water) or commercially available rat chow (with 4% NaCl in the diet), starting at 8 weeks of age. These results prompted us to analyze data from 5 earlier feeding trials using SHRSP rats. Overall, we found that SHRSP rats fed AIN-93G purified diet for 8 or 17 weeks did not demonstrate SRS (n = 18), whereas all SHRSP rats fed lab chow exhibited SRS at age 15.1 ± 0.6 weeks (n = 23). In addition, SHRSP rats fed lab chow had decreased mass gain starting at age 13 weeks, as well as decreased feed efficiencies after the first 5 weeks of feeding (p < 0.05). In conclusion, our data suggest that diet composition is a major contributor to the onset of stroke in SHRSP rats and that diet choice should be critically evaluated based on endpoint measures in the SHRSP model.