bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zebrafish (Danio rerio) as a possible bioindicator of epigenetic factors present in drinking water that may affect reproductive function: is chorion an issue?
Authors: Martinez-Sales M. , García-Ximénez F. , Espinós FJ. 
Published: March 2014

SummaryEmerging organic contaminants have been monitored in stream waters, raw and finished waters and wastewater effluents. Most of these contaminants, such as epigenetic substances, have been detected at very low levels. Unfortunately, their complete monitoring and/or removal are very difficult, given the increasing presence of new contaminants and due to analytical and economic considerations. For this reason, bioindicators are used as an alternative to monitor their presence. To this end, zebrafish is being used to assess certain contaminants in water quality studies.As our long-term aim is to determine if zebrafish (Danio rerio) can be used to detect environmental epigenetic factors in drinking waters with effects on human reproduction, an initial question is whether the chorion could interfere with the possible action of epigenetic factors in two reproductive events: genital ridge formation and migration of the primordial germ cells (PGCs) to these genital ridges.In the first experiment, we attempted to partially degrade the chorion of mid blastula transition (MBT) embryos with pronase, with acceptable survival rates at 5 days post fertilisation (dpf), with the group exposed for 15 min giving the best survival results. As denuded early embryos require a specific culture medium, in the next experiment embryo survival was evaluated when they were cultured up to 5 dpf in drinking waters from six different sources. Results showed a negative effect on embryo survival at 5 dpf from several waters but not in others, thus distorting the survival outcomes. These results suggest using embryos with the chorion intact from the outset when drinking waters from different sources are to be tested.
Eine Einführung in Impulskontrollstörungen bei Morbus Parkinson
Authors: Heldmann Marcus , Al-Khaled Mohamed , Hagenah Johann , Münte Thomas F. 
Published: March 2014

Impulskontrollstörungen werden bei Parkinson-Patienten vor allem im Zusammenhang mit der Medikation von Dopaminagonisten beobachtet und treten bei entsprechender Medikation in bis zu 17 % der Behandelten auf. Diese Störungen umfassen pathologisches Spielen, pathologisches Kaufen, Hypersexualität und die Binge-Eating Störung. Mit Hilfe bildgebender Verfahren konnte gezeigt werden, dass Dopaminagonisten zu einer Abschwächung der Reaktivität des Belohnungssystems auf Belohnungsreize führen. Ferner konnten bedeutsame Unterschiede in der Aktivität frontolimbischer Kontrollareale zwischen Parkinsonpatienten mit und ohne Impulskontrollstörungen festgestellt werden. Eine experimentell nachweisbare Konsequenz vermehrter Impulsivität bei Parkinson-Patienten ist eine stärkere Abwertung von in der Zukunft liegenden Gewinnen in so genannten intertemporal choice Aufgaben. Diese Übersicht schließt mit einer Diskussion der praktischen Konsequenzen für das Management von betroffenen Patienten.
Population Pharmacokinetics of Azithromycin in Whole Blood, Peripheral Blood Mononuclear Cells, and Polymorphonuclear Cells in Healthy Adults
Authors: Sampson MR , Dumitrescu TP , Brouwer KLR , Schmith VD 
Published: March 2014

Azithromycin's extensive distribution to proinflammatory cells, including peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs), may be important to its antimicrobial and anti‐inflammatory properties. The need to simultaneously predict azithromycin concentrations in whole blood (“blood”), PBMCs, and PMNs motivated this investigation. A single‐dose study in 20 healthy adults was conducted, and nonlinear mixed effects modeling was used to simultaneously describe azithromycin concentrations in blood, PBMCs, and PMNs (simultaneous PK model). Data were well described by a four‐compartment mamillary model. Apparent central clearance and volume of distribution estimates were 67.3 l/hour and 336 l (interindividual variability of 114 and 122%, respectively). Bootstrapping and visual predictive checks showed adequate model performance. Azithromycin concentrations in blood, PBMCs, and PMNs from external studies of healthy adults and cystic fibrosis patients were within the 5th and 95th percentiles of model simulations. This novel empirical model can be used to predict azithromycin concentrations in blood, PBMCs, and PMNs with different dosing regimens.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e103; doi: 10.1038/psp.2013.80; published online 5 March 2014
Duality of the murine CD8 compartment
Authors: Genolet Raphaël , Leignadier Julie , Østerås Magne , Farinelli Laurent , Stevenson Brian J. , Luescher Immanuel F. 
Published: March 2014

SignificanceCD8αβ is expressed on CD8+T cells and can govern their thymic selection, differentiation, and effector functions by inducing Ca2+and nuclear factor of activated T cells (NFAT)-dependent signaling. Conversely, we showed that CD8-independent T cells are signaled in a Ca2+-independent, PI3K-dependent manner. By assessing the physical and functional affinities, signaling, and TCR repertoires of CD8-dependent and -independent T cells, we uncovered correlates between effector functions, their triggering, and the TCR repertoires. We suggest that the docking orientations of TCR–MHC complexes may influence CD8+T-cell signaling and hence their functions. Together, these data argue that signaling events rather than affinity determine CD8 dependency and that the duality of the CD8 compartment may provide the organisms with broader protective immunity.
A Diel Flux Balance Model Captures Interactions between Light and Dark Metabolism during Day-Night Cycles in C3 and Crassulacean Acid Metabolism Leaves
Authors: Cheung C.Y. Maurice , Poolman Mark G. , Fell David. A. , Ratcliffe R. George , Sweetlove Lee J. 
Published: March 2014

Abstract
Although leaves have to accommodate markedly different metabolic flux patterns in the light and the dark, models of leaf metabolism based on flux-balance analysis (FBA) have so far been confined to consideration of the network under continuous light. An FBA framework is presented that solves the two phases of the diel cycle as a single optimization problem and, thus, provides a more representative model of leaf metabolism. The requirement to support continued export of sugar and amino acids from the leaf during the night and to meet overnight cellular maintenance costs forces the model to set aside stores of both carbon and nitrogen during the day. With only minimal constraints, the model successfully captures many of the known features of C3 leaf metabolism, including the recently discovered role of citrate synthesis and accumulation in the night as a precursor for the provision of carbon skeletons for amino acid synthesis during the day. The diel FBA model can be applied to other temporal separations, such as that which occurs in Crassulacean acid metabolism (CAM) photosynthesis, allowing a system-level analysis of the energetics of CAM. The diel model predicts that there is no overall energetic advantage to CAM, despite the potential for suppression of photorespiration through CO2 concentration. Moreover, any savings in enzyme machinery costs through suppression of photorespiration are likely to be offset by the higher flux demand of the CAM cycle. It is concluded that energetic or nitrogen use considerations are unlikely to be evolutionary drivers for CAM photosynthesis.
ATP Requirement for Chloroplast Protein Import Is Set by the K
m for ATP Hydrolysis of Stromal Hsp70 in Physcomitrella patens
Authors: Liu Li , McNeilage Robert T. , Shi Lan-xin , Theg Steven M. 
Published: March 2014

Abstract
The 70-kD family of heat shock proteins (Hsp70s) is involved in a number of seemingly disparate cellular functions, including folding of nascent proteins, breakup of misfolded protein aggregates, and translocation of proteins across membranes. They act through the binding and release of substrate proteins, accompanied by hydrolysis of ATP. Chloroplast stromal Hsp70 plays a crucial role in the import of proteins into plastids. Mutations of an ATP binding domain Thr were previously reported to result in an increase in the K m for ATP and a decrease in the enzyme's kcat. To ask which chloroplast stromal chaperone, Hsp70 or Hsp93, both of which are ATPases, dominates the energetics of the motor responsible for protein import, we made transgenic moss (Physcomitrella patens) harboring the K m-altering mutation in the essential stromal Hsp70-2 and measured the effect on the amount of ATP required for protein import into chloroplasts. Here, we report that increasing the K m for ATP hydrolysis of Hsp70 translated into an increased K m for ATP usage by chloroplasts for protein import. This thus directly demonstrates that the ATP-derived energy long known to be required for chloroplast protein import is delivered via the Hsp70 chaperones and that the chaperone's ATPase activity dominates the energetics of the reaction.
Levator ani muscle avulsion during childbirth: a risk prediction model
Authors: van Delft K , Thakar R , Sultan AH , Schwertner‐Tiepelmann N , Kluivers K 
Published: March 2014

ObjectiveTo establish the incidence of levator ani muscle (LAM) avulsion in primiparous women and to develop a clinically applicable risk prediction model.DesignObservational longitudinal cohort study.SettingDistrict General University Hospital, United Kingdom.SampleNulliparous women at 36 weeks of gestation and 3 months postpartum.MethodsFour‐dimensional transperineal ultrasound was performed during both visits. Tomographic ultrasound imaging at maximum contraction was used to diagnose no, minor or major LAM avulsion. A risk model was developed using multivariable ordinal logistic regression.Main outcome measuresIncidence of LAM avulsion and its risk factors.ResultsOf 269 women with no antenatal LAM avulsion 71% (n = 191) returned postpartum. No LAM avulsion was found after caesarean section (n = 48). Following vaginal delivery the overall incidence of LAM avulsion was 21.0% (n = 30, 95% confidence interval [95% CI] 15.1–28.4). Minor and major LAM avulsion were diagnosed in 4.9% (n = 7, 95% CI 2.2–9.9) and 16.1% (n = 23, 95% CI 10.9–23.0), respectively. Risk factors were obstetric anal sphincter injuries (odds ratio [OR] 4.4, 95% CI 1.6–12.1), prolonged active second stage of labour per hour (OR 2.2, 95% CI 1.4–3.3) and forceps delivery (OR 6.6, 95% CI 2.5–17.2). A risk model and nomogram were developed to estimate a woman's individual risk: three risk factors combined revealed a 75% chance of LAM avulsion.ConclusionsTwenty‐one percent of women sustain LAM avulsion during their first vaginal delivery. Our risk model and nomogram are novel tools to estimate individual chances of LAM avulsion. We can now target postnatal women at risk of sustaining a LAM avulsion.
Missed Opportunities for Diagnosis of Post‐traumatic Thrombosis: A Case Series and Literature Review
Authors: Hosseini Marzieh , Hedjazi Arya , Bahrani Mohammadreza 
Published: March 2014

AbstractThrombosis is caused by abnormalities in the composition of the blood, the quality of the vessel wall, and the nature of the blood flow. Herein, we present four cases of fatal thrombus formation after a trauma, which were missed at clinical diagnosis as the symptoms were misinterpreted. We stress that a blunt trauma can be fatal because of its direct and indirect kinetic energy effects at the subacute phase. This report highlights the importance of considering thrombosis in the diagnosis of closed trauma, which is usually missed because of lack of awareness for early diagnosis and treatment or is detected too late for any therapeutic intervention, which can result in avoidable morbidity and mortality.
ROS1 mutation and treatment with crizotinib in a 30‐year old Caucasian woman with stage IV non‐small cell lung cancer/adenocarcinoma and complete remission
Authors: Blaukovitsch Markus , Hofer Johann , Hutarew Georg , Müllauer Leonhard , Ingrid Simonitsch‐Klupp , Studnicka Michael 
Published: March 2014

AbstractIn this case report we describe a 30 year‐old Caucasian woman with a histopathological diagnosis of pulmonary adenocarcinoma in both lungs with lipidic and micropapillary growth pattern and ROS1 (C‐ros oncogene 1, receptor tyrosine kinase) rearrangement. There is evidence that crizotinib can be used for molecular target therapy in these patients. We enrolled the patient in an off‐label program for the treatment of ROS1 rearranged adenocarcinomas with the EML4/anaplastic lymphoma kinase inhibitor crizotinib. After a follow‐up of eight weeks we saw a complete remission in both lungs without any signs of metabolic tumor activity. This report shows the importance of testing young patients with adenocarcinomas of the lung for rare oncogenic driver mutations, such as ROS1, with possible molecular treatment options.
Cutaneous protothecosis in a patient with previously undiagnosed HIV infection
Authors: Fong Kenneth , Tee Shang‐Ian , Ho Madeline S L , Pan Jiun Yit 
Published: March 2014

AbstractProtothecosis is an uncommon condition resulting from infection by achlorophyllous algae of the Prototheca species. Immunocompromised individuals are generally most susceptible to protothecal infection and tend to develop severe and disseminated disease. However, the association between protothecosis and HIV‐induced immunosuppression is not clear, with only a handful of cases having been described to date. Here we report a case of cutaneous protothecosis in a Chinese man with previously undiagnosed HIV infection that responded well to oral itraconazole.
Systematic review with meta‐analysis: the incidence of advanced neoplasia after polypectomy in patients with and without low‐risk adenomas
Authors: Hassan C. , Gimeno‐García A. , Kalager M. , Spada C. , Zullo A. , Costamagna G. , Senore C. , Rex D. K. , Quintero E. 
Published: March 2014

SummaryBackgroundPatients with one to two tubular adenomas <1 cm in size without high‐grade dysplasia (low‐risk group) are considered at low risk for colorectal cancer. However, it is uncertain whether they have the same risk of subsequent advanced neoplasia as those with no neoplasia at baseline colonoscopy.AimTo compare incidence of metachronous advanced neoplasia between patients in the low‐risk adenoma group and those without neoplasia at index colonoscopy.MethodsRelevant publications were identified by MEDLINE/EMBASE and other databases for the period 1992–2013. Studies comparing the incidence of post‐polypectomy advanced neoplasia (adenomas ≥10 mm/high‐grade dysplasia/villous or cancer) between the low‐risk group and patients without colorectal neoplasia at the first colonoscopy were included. Detection rates for advanced neoplasia at endoscopic surveillance were extracted. Study quality was ascertained according to Newcastle–Ottawa Scale. Forest plot was produced based on random‐effect models. Inter‐study heterogeneity was assessed using the I2 statistic.ResultsSeven studies provided data on 11 387 patients. Mean surveillance periods ranged between 2 and 5 years. Altogether, 267 patients with post‐polypectomy advanced neoplasia were detected in the two groups. The incidence of advanced neoplasia was 1.6% (119/7308) in those without neoplasia and 3.6% (148/4079) in those with low‐risk adenoma, respectively, corresponding to a relative risk of 1.8 (95% CI: 1.3–2.6). Inter‐study heterogeneity was only moderate (I2: 37%). No publication bias was present.ConclusionsPatients with low‐risk adenomas at baseline had a higher risk of metachronous advanced neoplasia than the group with no adenomas at baseline, though the absolute risk was low in both groups.
Thiopurine monitoring in children with inflammatory bowel disease: a systematic review
Authors: Konidari Anastasia , Anagnostopoulos Antonios , Bonnett Laura J. , Pirmohamed Munir , El‐Matary Wael 
Published: March 2014

AimsThe aim was to systematically review the evidence on the clinical usefulness of thiopurine metabolite and white blood count (WBC) monitoring in the assessment of clinical outcomes in children with inflammatory bowel disease (IBD).MethodsMedline, Embase, Cochrane Central Register of controlled trials and http://www.clinicaltrials.gov were screened in adherence to the PRISMA statement by two independent reviewers for identification of eligible studies. Eligible studies were randomized controlled trials (RCTs), cohort studies and large case series of children with inflammatory bowel disease (IBD) (<18 years) who underwent monitoring of thiopurine metabolites and/or WBC.ResultsFifteen papers were identified (n = 1026). None of the eligible studies were RCTs. High 6‐thioguanine nucleotide (6TGN) concentrations were not consistently associated with leucopenia. Leucopenia was not associated with achievement of clinical remission. A positive but not consistent correlation between 6TGN and clinical remission was reported. Haematological toxicity could not be reliably assessed with 6TGN measurements only. A number of studies supported the use of high 6‐methylmercaptopurine ribonucleotides (6MMPR) as an indicator of hepatotoxicity. Low thiopurine metabolite concentration may be indicative of non‐compliance.ConclusionThiopurine metabolite testing does not safely predict clinical outcome, but may facilitate toxicity surveillance and treatment optimization in poor responders. Current evidence favours the combination of thiopurine metabolite/WBC monitoring and clinic follow‐up for prompt identification of haematologic/hepatic toxicity safe dose adjustment, and treatment modification in cases of suboptimal clinical outcome or non‐compliance. Well designed RCTs for the identification of robust surrogate markers of thiopurine efficacy and toxicity are required.
Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?
Authors: Greer Ian A. , Brenner Benjamin , Gris Jean‐Christophe 
Published: March 2014

SummaryHaemostatic and vascular biology mechanisms appear to play an important role in the pathogenesis of placenta‐mediated pregnancy complications. Although low‐dose aspirin (LDA) has a modest effect in preventing preeclampsia, antithrombotic interventions, LDA and low molecular weight heparin (LMWH) have not definitively proven their effectiveness in women with placenta‐mediated pregnancy complications selected by previous pregnancy outcome alone. Given the heterogeneous aetiology of placenta‐mediated pregnancy complications, it is critical to stratify patients according to maternal and fetal characteristics and disease mechanisms rather than simply by pregnancy outcome, such as miscarriage. Such stratification could identify those who could benefit from antithrombotic interventions in pregnancy. We lack data on genome‐wide association studies, biomarkers and trials of interventions applied to specific homogeneous populations. Future studies should focus on elaborating different disease mechanisms and examining antithrombotic interventions in specific and more homogeneous groups, such as thrombophilic women with well‐characterized placenta‐mediated pregnancy complications, stratified by disease severity and pathological findings. Because of fetal safety concerns with new anticoagulants, the intervention should focus on heparins alone or in combination with LDA. Thus, placenta‐mediated pregnancy complications deserve precision medicine, defining disease by mechanism rather than outcome with interventions focused on a more personalized approach.
Endocrine profiles in 693 elite athletes in the postcompetition setting
Authors: Healy M. L. , Gibney J. , Pentecost C. , Wheeler M. J. , Sonksen P. H. 
Published: March 2014

SummaryObjectiveTo measure a profile of hormones in a group of elite athletes. Increasing awareness of the widespread use of hormones as performance‐enhancing agents focusses attention on what may be considered as normal in this unusual group.DesignBlood samples were obtained from 813 volunteer elite athletes from a cross‐section of 15 sporting categories. An endocrine profile was measured on a subset of 693.ParticipantsVolunteer elite athletes. Samples were drawn within two hours of an event at a major national or international competition.MeasurementsDemographics and hormone profiles were obtained on 454 male and 239 female elite athletes.ResultsHormone profiles showed significant differences in 19 of the 24 measured variables between sexes and between all of the 15 sporting disciplines in men and 11 out of 24 in women. 16·5% of men had low testosterone levels, whereas 13·7% of women had high levels with complete overlap between the sexes. Women had a lean body mass 85% that of men – sufficient to account for sex differences in performance. There were highly significant correlations between many of the measured hormones.ConclusionsHormone profiles from elite athletes differ from usual reference ranges. Individual results are dependent on a number of factors including age, gender and physique. Differences in profiles between sports suggest that an individual's profile may contribute to his/her proficiency in a particular sport. The IOC definition of a woman as one who has a ‘normal’ testosterone level is untenable.
Bone tissue modelling and remodelling following guided bone regeneration in combination with biphasic calcium phosphate materials presenting different microporosity
Authors: Dahlin Christer , Obrecht Marcel , Dard Michel , Donos Nikos 
Published: March 2014

AbstractObjectivesThe aim of this study was to investigate bone regeneration following application of a novel biphasic calcium phosphate (BCP I) composed of microstructured granules of 90% β‐tricalcium phosphate (β‐TCP)/10% hydroxyapatite (HA) compared to BCP non‐microstructured biphasic calcium phosphate with a composite of 60% hydroxyapatite/40% β‐TCP (BCP II) and a deproteinized bovine bone mineral (DBBM) at surgically created defects in the mandible of minipigs in a combined approach with guided bone regeneration (GBR).Material and methodsSixteen minipigs were used for the study. Lower premolars P2, P3, P4 and first molar M1 were extracted. Following 3 months of healing, two defects with a width and depth of 7 mm were created bilaterally in the mandible. The different grafting materials were randomly placed in the created defects and covered by means of a collagen membrane. After 3 and 8 weeks, biopsies were sampled. All specimens were evaluated with descriptive histology and histomorphometric evaluations complemented by micro‐CT scan analysis.ResultsAll three biomaterials presented with higher bone volume at 8 weeks compared to 3 weeks (P < 0.0442). BCP I and DBBM demonstrated a significant higher amount of bone formation compared to BCP II at 8 weeks (P < 0.0328). BCP I also demonstrated a significant higher percentage of remaining graft volume compared to the other test groups both at 3 and 8 weeks (P < 0.0001 to P < 0.0003). Congruently, defects containing BCP I showed a significant higher amount of mineralized tissue compared to the other groups.ConclusionsAll the three test materials performed well with regard to bone formation at 8 weeks. BCP I showed significant higher amounts of newly formed bone despite a higher remaining graft volume compared to the other groups. With regard to the regenerative outcome, all the three materials can be recommended for clinical use.