bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of the multitarget compound DPH‐4 on human SSAO/VAP‐1‐expressing hCMEC/D3 cells under oxygen–glucose deprivation conditions: an in vitro experimental model of cerebral ischaemia
Authors: Sun P , Esteban G , Inokuchi T , Marco‐Contelles J , Weksler B B , Romero I A , Couraud P O , Unzeta M , Solé M 
Published: September 2015

AbstractBackground and PurposeStroke and Alzheimer's disease (AD) are related pathologies in which the cerebrovascular system is involved. Plasma levels of semicarbazide‐sensitive amine oxidase/vascular adhesion protein 1 (SSAO/VAP‐1, also known as Primary Amine Oxidase ‐PrAO) are increased in both stroke and AD patients and contribute to the vascular damage. During inflammation, its enzymatic activity mediates leukocyte recruitment to the injured tissue, inducing damage in the blood‐brain barrier (BBB) and neuronal tissue. We hypothesized that by altering cerebrovascular function, SSAO/VAP‐1 might play a role in the stroke–AD transition. Therefore, we evaluated the protective effect of the novel multitarget‐directed ligand DPH‐4, initially designed for AD therapy, on the BBB.Experimental ApproachA human microvascular brain endothelial cell line expressing human SSAO/VAP‐1 was generated, as the expression of SSAO/VAP‐1 is lost in cultured cells. To simulate ischaemic damage, these cells were subjected to oxygen and glucose deprivation (OGD) and re‐oxygenation conditions. The protective role of DPH‐4 was then evaluated in the presence of methylamine, an SSAO substrate, and/or β‐amyloid (Aβ).Key ResultsUnder our conditions, DPH‐4 protected brain endothelial cells from OGD and re‐oxygenation‐induced damage, and also decreased SSAO‐dependent leukocyte adhesion. DPH‐4 was also effective at preventing the damage induced by OGD and re‐oxygenation in the presence of Aβ as a model of AD pathology.Conclusions and ImplicationsFrom these results, we concluded that the multitarget compound DPH‐4 might be of therapeutic benefit to delay the onset and/or progression of the neurological pathologies associated with stroke and AD, which appear to be linked.
Exposure to a farm environment is associated with T helper 1 and regulatory cytokines at age 4.5 years
Authors: Kääriö H. , Huttunen K. , Karvonen A. M. , Schaub B. , von Mutius E. , Pekkanen J. , Hirvonen M.‐R. , Roponen M. 
Published: September 2015

SummaryBackgroundFarm exposure has been shown to protect from childhood asthma and allergic diseases, but underlying immunological mechanisms are not clear yet.ObjectiveTo explore whether farming lifestyle determines cytokine profile of peripheral blood mononuclear cells (PBMCs) of 4.5‐year‐old children (n = 88) from the Finnish PASTURE birth cohort study.MethodsWe analysed regulatory (IL‐10, IL‐2), T helper 1 (Th1)‐associated (IL‐12, IFN‐γ), inflammatory (IL‐1β, TNF, CXCL8) and Th2‐associated (IL‐13) cytokines in unstimulated PBMCs and after a short‐term (5 h) stimulation with lipopolysaccharide (LPS). Specific farm exposures (stables, hay barn, farm milk) at age 4 years were assessed from questionnaires.ResultsThe unstimulated PBMCs of farm children produced more IL‐10 (GMR 1.22, P = 0.032), IL‐12 (GMR 1.24, P = 0.012) and IFN‐γ (GMR 1.24, P = 0.024) than those of non‐farm children. Also, specific farm exposures were associated with higher spontaneous production of cytokines. The number of specific farm exposures tended to be dose dependently associated with higher spontaneous production of IFN‐γ (test for trends, P = 0.013) and lower LPS‐induced production of TNF (test for trends, P = 0.025).Conclusion and Clinical RelevanceFarming lifestyle seemed to be associated with increased spontaneous production of Th1 and regulatory cytokines. Decreased TNF responses to short‐term LPS stimulation in farm‐exposed children may imply tolerogenic immune mechanisms. These novel findings might contribute to the asthma and allergy protection in farm environment.
High nodal positivity rates even in good clinical responders after chemoradiation of rectal cancer: is organ preservation feasible?
Authors: Vallam K. C. , Engineer R. , Desouza A. , Patil P. , Saklani A. 
Published: September 2015

AbstractAimLocal excision (LE) is emerging as a treatment option for rectal cancer responding well to chemoradiation. However, it does not address the mesorectal nodal burden. We aimed to identify the factors influencing nodal positivity and subsequently defined a low‐risk group by including only patients at low risk.MethodA single‐centre, retrospective database analysis was carried out of patients with radically resected rectal cancer after neoadjuvant chemoradiation.ResultsThis study included 524 patients with predominantly low rectal tumours. Nodal positivity among ypT0, T1 and T2 groups was 14.7%, 28% and 30%, respectively. Multivariate analysis with stepwise logistic regression identified the following low‐risk features: age ≥ 40 years, nonsignet ring cell carcinoma (SRCC) histology and pathological complete response (pCR). Sixty‐nine patients fulfilling all three criteria were analysed and the nodal positivity was found to be 10.1%, which implies that, if these patients had been selected for LE, one in 10 would have had positive mesorectal nodes.ConclusionEven in patients with low‐risk criteria (pCR, non‐SRCC histology and age ≥ 40 years), the residual positive nodal disease burden is 10%. Whether this high incidence of residual nodal disease translates into a similar risk of locoregional recurrence if an organ‐preservation strategy is adopted is unclear.
Prophylactic levofloxacin in pediatric neutropenic patients during autologous hematopoietic stem cell transplantation
Authors: Hafez Hanafy Ahmed , Yousif Dalia , Abbassi Maggie , Elborai Yasser , Elhaddad Alaa 
Published: September 2015

AbstractBackgroundUsing fluoroquinolone prophylaxis in pediatric neutropenic patients is a controversial issue due to the concern about emergence of resistant strains in addition to the lack of pediatric studies. This study was performed to assess the effectiveness of levofloxacin prophylaxis in pediatric patients during autologous stem cell transplantation.MethodsThis was an observational study of pediatric patients who underwent autologous stem cell transplantation, comparing patients who received levofloxacin prophylaxis to historical controls.ResultsA total of 96 patients were included (46 patients in the control group and 50 patients received levofloxacin). The median duration till onset of first fever was 11 d in the control group as compared to 15 d in patients who received levofloxacin (p ≤ 0.001). The incidence of infectious complications was higher in patients without levofloxacin (4/46) than those with levofloxacin (1/50). The median duration of empirical antibiotic use was 10 d in the levofloxacin group compared with 14 d in the control group (p < 0.001).ConclusionLevofloxacin prophylaxis delayed first spike of fever, decreased the incidence of septic complications, and shortened the duration of empiric antibiotic use, but its impact on emergence of resistant organisms should be closely monitored.
Pathogenesis of osteochondrosis dissecans: How does this translate to management of the clinical case?
Authors: van Weeren P. R. , Olstad K. 
Published: September 2015

SummaryOsteochondrosis (OC) is the most prevalent developmental orthopaedic disease in the horse. It is a complex disorder because of the interplay of factors that influence the formation of lesions and the ensuing natural healing process, the end result of which determines clinical outcome. The early pathogenetic mechanism ofOChas long remained elusive, but recent research has provided compelling evidence for vascular disturbances leading to areas of ischaemic necrosis in the subarticular growth cartilage as the primary event. The aetiological factors that influence the process of the development of lesions are many and comprise both genetic and environmental factors. The genetic background ofOC(dissecans) is highly complex with quantitative trait loci associated with some form ofOCfound on not fewer than 22 of the 33 chromosomes of the horse, and different manifestations and locations ofOChaving probably different genetic backgrounds. The environmental factors can be divided into nutritional factors and factors influencing the biomechanical loading of joints. Feeding large quantities of easily digestible carbohydrates is a clear risk factor and also the availability of sufficient copper for mares in the last part of pregnancy is important. Factors influencing the biomechanical loading of joints include the exercise regimen of foals, paddock size and roughness of terrain, and conformation. EquineOCis rarely a life‐threatening disease and the prognosis of (surgical) treatment is good to very good. However, the impact on economics of the equine industry and on horse welfare is large. This impact can only be lessened by the judicious management of both horse breeding and horse husbandry. Some of the measures that would alleviate the burden ofOCconflict with (commercial) pressures from the industry and a balance between human‐imposed breeding and performance goals and the interest of the animal itself should be sought.
Comparison between different D‐Dimer cutoff values to assess the individual risk of recurrent venous thromboembolism: analysis of results obtained in the DULCIS study
Authors: Palareti G. , Legnani C. , Cosmi B. , Antonucci E. , Erba N. , Poli D. , Testa S. , Tosetto A. ,   the DULCIS (D‐dimer‐ULtrasonography in Combination Italian Study) Investigators (See Appendix)
Published: September 2015

SummaryIntroductionD‐dimer assay, generally evaluated according to cutoff points calibrated for VTE exclusion, is used to estimate the individual risk of recurrence after a first idiopathic event of venous thromboembolism (VTE).MethodsCommercial D‐dimer assays, evaluated according to predetermined cutoff levels for each assay, specific for age (lower in subjects <70 years) and gender (lower in males), were used in the recent DULCIS study. The present analysis compared the results obtained in the DULCIS with those that might have been had using the following different cutoff criteria: traditional cutoff for VTE exclusion, higher levels in subjects aged ≥60 years, or age multiplied by 10.ResultsIn young subjects, the DULCIS low cutoff levels resulted in half the recurrent events that would have occurred using the other criteria. In elderly patients, the DULCIS results were similar to those calculated for the two age‐adjusted criteria. The adoption of traditional VTE exclusion criteria would have led to positive results in the large majority of elderly subjects, without a significant reduction in the rate of recurrent event.ConclusionThe results confirm the usefulness of the cutoff levels used in DULCIS.
Developmental Change in Infants' Detection of Visual Faces that Match Auditory Vowels
Authors: Streri Arlette , Coulon Marion , Marie Julien , Yeung H. Henny 
Published: September 2015

Infants demonstrate robust audiovisual (AV) perception, detecting, for example, which visual face matches auditory speech in many paradigms. For simple phonetic segments, like vowels, previous work has assumed developmental stability in AV matching. This study shows dramatic differences in matching performance for different vowels across the first year of life: 3‐, 6‐, and 9‐month‐olds were familiarized for 40 sec with a visual face articulating a vowel in synchrony with auditory presentations of that vowel, but crucially, the mouth of the face was occluded. At test, infants were shown two still photos of the same face without occlusion for 1 min in silence. One face had a static articulatory configuration matching the previously heard vowel, while the other face had a static configuration matching a different vowel. Three auditory vowels were used: /a/, /i/, and /u/. Results suggest that AV matching performance varies according to age and to the familiarized vowel. Interestingly, results are not linked to the frequency of vowels in auditory input, but may instead be related to infants' ability to produce the target vowel. A speculative hypothesis is that vowel production in infancy modulates AV vowel matching.
Association of periodontitis with persistent, pro‐atherogenic antibody responses
Authors: Buhlin Kåre , Holmer Jacob , Gustafsson Anders , Hörkkö Sohvi , Pockley Alan Graham , Johansson Anders , Paju Susanna , Klinge Björn , Pussinen Pirkko J. 
Published: September 2015

AbstractAimTo study antibody responses associated with molecular mimicry in periodontitis.Material & MethodsFifty‐four periodontitis cases (mean age 54.0 years) and 44 controls (53.6 years) were examined, after which cases received periodontal treatment. Established immunoassays were used to analyse levels of antibodies against two pathogens, Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg), heat shock proteins (Hsp), Hsp60, Hsp65, and Hsp70, and epitopes of oxidized low‐density lipoprotein (oxLDL) (CuOx‐LDL and MDA‐LDL) in plasma samples that were collected at baseline and after 3 (n = 48) and 6 (n = 30) months.ResultsWhen age, sex, smoking habit, and the number of teeth were considered in multivariate logistic regressions, Aa and Pg IgG, Hsp65‐IgA, CuOx‐LDL‐IgG and ‐IgM, and MDA‐LDL‐IgG antibody levels were associated with periodontitis, whereas Hsp60‐IgG2 antibody levels were inversely associated. The Aa antibody levels significantly correlated with the levels of IgA antibodies to Hsp65 and Hsp70, and both OxLDL IgA antibody levels. The levels of antibodies to Pg correlated with IgG antibodies to Hsp60, Hsp70, and both oxLDL antibody epitopes. None of the antibody levels changed significantly after treatment.ConclusionsPeriodontitis is associated with persistently high levels of circulating antibodies that are reactive with pathogen‐ and host‐derived antigens.
Bone reconstruction after surgical treatment of experimental peri‐implantitis defects at a sandblasted/acid‐etched hydroxyapatite‐coated implant: an experimental study in the dog
Authors: Namgoong Hee , Kim Myung duck , Ku Young , Rhyu In‐Chul , Lee Yong Moo , Seol Yang Jo , Gu Hee jin , Susin Cristiano , Wikesjö Ulf ME , Koo Ki‐Tae 
Published: September 2015

AbstractObjectivesThe objective of this study was to evaluate bone formation/osseointegration following surgical treatment of experimental peri‐implantitis at dental implants with different surface characteristics exposed to ligature‐induced breakdown conditions.MethodsTen turned (control), 10 sandblasted/acid‐etched (SA), and 10 SA/hydroxyapatite nanocoated (HA) implants were installed into the edentulated posterior mandible in five Beagle dogs and allowed to osseointegrate for 12 weeks. Ligature‐induced breakdown defects were then induced over 23 weeks using stainless steel wire ligatures. The ligatures were removed and soft tissues were allowed to heal for 3 weeks. Next, exposed implant surfaces were decontaminated followed by guided bone regeneration using a collagen membrane and submerged wound healing. The animals were euthanized for histometric analysis at 12 weeks post‐surgery.ResultsThe radiographic analysis showed vertical bone loss following ligature‐induced breakdown without statistically significant differences among implant technologies. The histometric analysis showed significantly enhanced bone formation (height) at SA and SA/HA compared with turned implants (p = 0.028) following reconstructive surgery. Bone formation area was greater at SA/HA compared with turned implants, however the difference did not reach statistical significance.ConclusionsWhile ligature‐induced defect progression does not appear implant surface dependent in this animal model, bone formation at the decontaminated implant surfaces appears more favourable at SA and SA/HA over turned implants following reconstructive surgery.
Elevational speciation in action? Restricted gene flow associated with adaptive divergence across an altitudinal gradient
Authors: Funk W. C. , Murphy M. A. , Hoke K. L. , Muths E. , Amburgey S. M. , Lemmon E. M. , Lemmon A. R. 
Published: September 2015

AbstractEvolutionary theory predicts that divergent selection pressures across elevational gradients could cause adaptive divergence and reproductive isolation in the process of ecological speciation. Although there is substantial evidence for adaptive divergence across elevation, there is less evidence that this restricts gene flow. Previous work in the boreal chorus frog (Pseudacris maculata) has demonstrated adaptive divergence in morphological, life history and physiological traits across an elevational gradient from approximately 1500–3000 m in the Colorado Front Range, USA. We tested whether this adaptive divergence is associated with restricted gene flow across elevation – as would be expected if incipient speciation were occurring – and, if so, whether behavioural isolation contributes to reproductive isolation. Our analysis of 12 microsatellite loci in 797 frogs from 53 populations revealed restricted gene flow across elevation, even after controlling for geographic distance and topography. Calls also varied significantly across elevation in dominant frequency, pulse number and pulse duration, which was partly, but not entirely, due to variation in body size and temperature across elevation. However, call variation did not result in strong behavioural isolation: in phonotaxis experiments, low‐elevation females tended to prefer an average low‐elevation call over a high‐elevation call, and vice versa for high‐elevation females, but this trend was not statistically significant. In summary, our results show that adaptive divergence across elevation restricts gene flow in P. maculata, but the mechanisms for this potential incipient speciation remain open.
Ex vivo lymphocyte phenotyping during Plasmodium falciparum sporozoite immunization in humans
Authors: Bijker E. M. , Schats R. , Visser L. G. , Sauerwein R. W. , Scholzen A. 
Published: September 2015

SummaryImmunization of malaria‐naïve volunteers under chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) efficiently and reproducibly induces sterile protection and thus constitutes an excellent model to study protective immune responses against malaria. Here, we performed the first longitudinal assessment of lymphocyte activation and differentiation kinetics during sporozoite immunization in 15 volunteers by ex vivo lymphocyte flow cytometry analysis. Both CD4 and CD8 T cells as well as γδT cells, NK cells and CD3+ CD56+ cells showed increased activation and proliferation following immunization. Transient induction of the transcription factor T‐bet and the cytotoxic molecule granzyme B indicated a role of Th1 responses and cytotoxic T cells in CPS‐induced immunity. The absolute number of γδT cells as well as the proportion of granzyme B‐containing γδT cells showed a significant and sustained increase. Regulatory T‐cell (Treg) proliferation was significantly higher after the second immunization in subjects subsequently not protected against challenge infection. These findings indicate an important role for γδT cells, Th1 and cytotoxic responses in whole sporozoite immunization with a possibly suppressive role of Tregs.
Reduced protein availability by albumen removal during chicken embryogenesis decreases body weight and induces hormonal changes
Authors: Willems Els , Wang Yufeng , Koppenol Astrid , Lesuisse Jens , Franssens Lies , Decuypere Eddy , Buyse Johan , Everaert Nadia 
Published: September 2015

New Findings

What is the central question of this study?
Prenatal protein undernutrition by albumen removal in an avian model of fetal programming leads to long‐term programming effects, but when do these effects first appear and are these programming effects regulated by the same candidate genes as in mammals?

What is the main finding and its importance?
The present results indicate that prenatal protein undernutrition by albumen removal induces phenotypical and hormonal changes in the early posthatch period, when the mismatch between the prenatal and postnatal environment first arises, but these changes are not accompanied by an altered gene expression of the selected candidate genes.

Studies of the chicken offer a unique model for investigation of the direct effects of reduced prenatal protein availability by the partial replacement of albumen with saline in eggs at embryonic day 1 (albumen‐deprived group). The results were compared with mock‐treated sham chicks and non‐treated control chicks. Although no differences in hatch weight were found, body weight and growth were reduced in the albumen‐deprived chicks until 3 weeks of age. The feed intake of the albumen‐deprived chicks, however, was increased compared with the control (day 13–21) and the sham chicks (day 16–18). In the albumen‐deprived chicks, the ratio of thyroxine to 3,5,3′‐triiodothyronine in the plasma was increased compared with the control chicks, whereas the plasma corticosterone level was increased only at day 7 compared with both other groups. The plasma glucose concentration and glucose tolerance were not affected by treatment. Several candidate genes previously associated with effects of prenatal protein deprivation in mammals were examined in the liver of newly hatched chicks. Gene expression of glycogen synthase 2, glycogen phosphorylase 1, peroxisome proliferator‐activated receptor α and γ and glucocorticoid receptor was not affected by the treatment. In conclusion, reduction of prenatal protein availability led to differences in body weight and influenced hormones involved in metabolism and growth. Gene expression of the selected candidate genes was not altered, in contrast to mammals.
Metabolic Engineering of a Novel Muconic Acid Biosynthesis Pathway via 4-Hydroxybenzoic Acid in Escherichia coli
Authors: Sengupta Sudeshna , Jonnalagadda Sudhakar , Goonewardena Lakshani , Juturu Veeresh 
Published: September 2015

ABSTRACT

cis
,
cis
-Muconic acid (MA) is a commercially important raw material used in pharmaceuticals, functional resins, and agrochemicals. MA is also a potential platform chemical for the production of adipic acid (AA), terephthalic acid, caprolactam, and 1,6-hexanediol. A strain of
Escherichia coli
K-12, BW25113, was genetically modified, and a novel nonnative metabolic pathway was introduced for the synthesis of MA from glucose. The proposed pathway converted chorismate from the aromatic amino acid pathway to MA via 4-hydroxybenzoic acid (PHB). Three nonnative genes,
pobA
,
aroY
, and
catA
, coding for 4-hydroxybenzoate hydrolyase, protocatechuate decarboxylase, and catechol 1,2-dioxygenase, respectively, were functionally expressed in
E. coli
to establish the MA biosynthetic pathway.
E. coli
native genes
ubiC
,
aroF
FBR
,
aroE
, and
aroL
were overexpressed and the genes
ptsH
,
ptsI
,
crr
, and
pykF
were deleted from the
E. coli
genome in order to increase the precursors of the proposed MA pathway. The final engineered
E. coli
strain produced nearly 170 mg/liter of MA from simple carbon sources in shake flask experiments. The proposed pathway was proved to be functionally active, and the strategy can be used for future metabolic engineering efforts for production of MA from renewable sugars.