bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gata3 hypermethylation and Foxp3 hypomethylation are associated with sustained protection and bystander effect following epicutaneous immunotherapy in peanut‐sensitized mice
Authors: Mondoulet L. , Dioszeghy V. , Busato F. , Plaquet C. , Dhelft V. , Bethune K. , Leclere L. , Daviaud C. , Ligouis M. , Sampson H. , Dupont C. , Tost J. 
Published: May 2018

AbstractBackgroundEpicutaneous immunotherapy (EPIT) is a promising method for treating food allergies. In animal models, EPIT induces sustained unresponsiveness and prevents further sensitization mediated by Tregs. Here, we elucidate the mechanisms underlying the therapeutic effect of EPIT, by characterizing the kinetics of DNA methylation changes in sorted cells from spleen and blood and by evaluating its persistence and bystander effect compared to oral immunotherapy (OIT).MethodsBALB/c mice orally sensitized to peanut proteins (PPE) were treated by EPIT using a PPE‐patch or by PPE‐OIT. Another set of peanut‐sensitized mice treated by EPIT or OIT were sacrificed following a protocol of sensitization to OVA. DNA methylation was analyzed during immunotherapy and 8 weeks after the end of treatment in sorted cells from spleen and blood by pyrosequencing. Humoral and cellular responses were measured during and after immunotherapy.ResultsAnalyses showed a significant hypermethylation of the Gata3 promoter detectable only in Th2 cells for EPIT from the 4th week and a significant hypomethylation of the Foxp3 promoter in CD62L+ Tregs, which was sustained only for EPIT. In addition, mice treated with EPIT were protected from subsequent sensitization and maintained the epigenetic signature characteristic for EPIT.ConclusionsOur study demonstrates that EPIT leads to a unique and stable epigenetic signature in specific T‐cell compartments with downregulation of Th2 key regulators and upregulation of Treg transcription factors, likely explaining the sustainability of protection and the observed bystander effect.
Children who face development risks due to maternal addiction during pregnancy require extra medical and psychosocial resources
Authors: Rangmar Jenny , Lilja Maria , Köhler Marie , Reuter Antonia 
Published: May 2018

AbstractAimThis study examined medical and psychosocial risk factors in children born to women with addiction problems during pregnancy and the children's needs for extra medical and psychosocial resources.MethodsSwedish midwives routinely screen pregnant women for drugs and alcohol and refer women with addictions to the Maternity and Child Healthcare Resource Team. We investigated the medical records of 127 children (51% girls) whose mothers were referred to the Resource Team from 2009 to 2015. Additional data were obtained from local child healthcare services (CHS), which provide routine paediatric care.ResultsMore than three‐quarters (76%) of the children had prenatal exposure to alcohol and drugs, and 17% were born with withdrawal symptoms. The mothers had a high rate of psychiatric diagnoses (38%) and were more likely to smoke after delivery and less likely to breastfeed than the general population. However, adherence to the CHS programme was generally high. Additional visits to the nurse, referrals to specialists, collaboration meetings and reports of concerns to social services decreased when the children began attending ordinary CHS centres.ConclusionChildren born to women with addictions during pregnancy faced a high risk of developmental problems and should be offered additional CHS resources to minimise negative long‐term consequences.
The analgesic efficacy and pharmacokinetics of epidural oxycodone after gynaecological laparotomy: a randomized, double‐blind, double‐dummy comparison with intravenous administration
Authors: Piirainen Panu , Kokki Hannu , Hautajärvi Heidi , Ranta Veli‐Pekka , Kokki Merja 
Published: May 2018

AimThe aim of the present study was to compare the analgesic efficacy of epidural and intravenous (i.v.) oxycodone at the same dose.MethodsIn this randomized, double‐blind, double‐dummy clinical trial, 30 women, aged 24–67 years, undergoing elective gynaecological laparotomy, were administrated either i.v. saline and epidural oxycodone 0.1 mg·kg−1 (EPI group; n = 15) or i.v. oxycodone 0.1 mg·kg−1 and epidural saline (IV group; n = 15). For multimodal analgesia, patients received i.v. paracetamol and dexketoprofen, and a triple‐mixture epidural infusion after the first 4 h postoperatively. The primary outcome was the total dose of i.v. fentanyl for rescue analgesia during the first 4 h postoperatively.ResultsAll patients required fentanyl during the first 4 h. The median number of fentanyl doses were three (quartiles 1, 8) in the EPI group and seven (6, 9) in the IV group (mean difference 3.1; 95% confidence interval 0.9, 5.2; P = 0.01). After the first 4 h, the two groups needed a similar total dose of epidural infusion. Patient satisfaction was similarly high in both groups, and both administration routes were well tolerated.ConclusionsThe data support the superiority of epidural oxycodone compared with that of i.v. administration in pain management after laparotomy.
Conditioned Reward of Opioids, but not Psychostimulants, is Impaired in GABA‐A Receptor δ Subunit Knockout Mice
Authors: Siivonen Milo S. , de Miguel Elena , Aaltio Juho , Manner Aino K. , Vahermo Mikko , Yli‐Kauhaluoma Jari , Linden Anni‐Maija , Aitta‐aho Teemu , Korpi Esa R. 
Published: May 2018

AbstractExtrasynaptic δ subunit‐containing γ‐aminobutyric acid type A receptors (δ‐GABAARs) are emerging as targets for a number of neuropsychopharmacological drugs, including the direct GABA site agonist gaboxadol and neuroactive steroids. Among other regions, these δ‐GABAARs are functionally expressed in the ventral tegmental area (VTA), the cell body region of mesocorticolimbic dopamine (DA) system important for motivated behaviours, and in the target region, the nucleus accumbens. Gaboxadol and neurosteroids induce VTA DA neuron plasticity ex vivo, by inhibiting the VTA GABA neurons, and aversive place conditioning, which are absent in the δ‐GABAAR knockout mice (δ‐KO). It is not known whether δ‐GABAARs are important for the effects of other drugs, such as opioids (that also inhibit GABA neurons) and stimulants (that primarily elevate monoamine levels). Here, we used δ‐KO mice and conditioned place preference (CPP) test to study the rewarding effects of morphine (20 mg/kg), methamphetamine (1 mg/kg) and mephedrone (5 mg/kg). Morphine‐induced nociception was also assessed using tail‐flick and hot‐plate tests. We found that the δ‐KO mice failed to express morphine‐induced CPP, but that they were more sensitive to morphine‐induced analgesia in the tail‐flick test. In contrast, stimulant‐induced CPP in the δ‐KO mice was similar to that in the wild‐type controls. Thus, the conditioned rewarding effect by opioids, but not that of stimulants, was impaired in the absence of δ‐GABAARs. Further studies are warranted to assess the potential of δ‐GABAAR antagonists as possible targets for reducing morphine reward and potentiating morphine analgesia.
REGIME DEPENDENT EFFECT OF OUTPUT GROWTH ON OUTPUT GROWTH UNCERTAINTY: EVIDENCE FROM OECD COUNTRIES
Authors: Chowdhury Kushal Banik , Sarkar Nityananda 
Published: May 2018

ABSTRACTThis paper studies the impact of output growth on output growth uncertainty by considering two important issues hitherto not properly and adequately addressed to in the existing empirical studies specifying this relationship. These are: (i) the possible existence of a threshold level of output growth, and the consequent identification of two regimes characterized by high and low output growth, and (ii) whether or not the coefficient capturing the causal link is different in these two output growth states. This paper proposes a regime switching model to study this asymmetric effect for 16 OECD countries. Based on monthly time‐series observations, our results strongly support that the impact varies significantly between the two output growth regimes with the coefficient in the high growth regime being negative for majority of the countries.
Luteolin ameliorates rat myocardial ischaemia–reperfusion injury through activation of peroxiredoxin II
Authors: Wei Bo , Lin Qiao , Ji Ya‐Ge , Zhao Yi‐Can , Ding Li‐Na , Zhou Wen‐Juan , Zhang Li‐Hua , Gao Chuan‐Yu , Zhao Wen 
Published: May 2018

Background and PurposeAntioxidants provide a promising therapeutic effect for the cardiovascular disease. Luteolin, a polyphenolic bioflavonoid, is known to confer cardioprotection, although the underlying mechanisms, especially the role of luteolin on the antioxidant enzymes, such as the peroxiredoxin family, remain unknown.Experimental ApproachWe measured the effects of luteolin on myocardial ischaemia/reperfusion (MI/R) injury in vivo (Sprague‐Dawley rats) and in vitro, together with the underlying mechanisms, with a focus on signalling by peroxiredoxins. H9c2 cells were used to assess the changes in peroxiredoxins and the other antioxidant enzymes. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also assayed.Key ResultsLuteolin exerted significant cardioprotective effects in vivo and in vitro via improving cardiac function, increasing the expression of anti‐apoptotic protein Bcl‐2 and decreasing the pro‐apoptotic protein Bax and active caspases 3 and 9, associated with MI/R. Mechanistically, luteolin markedly enhanced expression of peroxiredoxin II, without significant effects on other forms of peroxiredoxin, catalase or SOD1. Molecular docking showed that luteolin could indeed bind to the enzymic active pocket of peroxiredoxin II. Furthermore, down‐regulation of peroxiredoxin II by peroxiredoxin II‐antisense, administered by adenovirus infection of H9c2 cardiomyocytes, and inhibition of peroxiredoxin II in vivo significantly reversed the cardioprotective effects of luteolin.Conclusions and ImplicationsOur findings, for the first time, demonstrate that luteolin protects against MI/R injury through promoting signalling through the endogenous antioxidant enzyme, peroxiredoxin II, indicating the important beneficial role of this antioxidant system in the heart.
Specialist perioperative allergy clinic services in the UK 2018: Results from the Royal College of Anaesthetists Sixth National Audit Project (NAP6) investigation of perioperative anaphylaxis
Authors: Egner W. , Cook T. M. , Garcez T. , Marinho S. , Kemp H. , Lucas D. N. , Floss K. , Farooque S. , Torevell H. , Thomas M. , Ferguson K. , Nasser S. , Karanam S. , Kong K.‐L. , McGuire N. , Bellamy M. , Warner A. , Hitchman J. , Farmer L. , Harper N. J. N. 
Published: May 2018

SummaryBackgroundThe Royal College of Anaesthetists 6th National Audit Project examined Grade 3‐5 perioperative anaphylaxis for 1 year in the UK.ObjectiveTo describe the causes and investigation of anaphylaxis in the NAP6 cohort, in relation to published guidance and previous baseline survey results.MethodsWe used a secure registry to gather details of Grade 3‐5 perioperative anaphylaxis. Anonymous reports were aggregated for analysis and reviewed in detail. Panel consensus diagnosis, reaction grade, review of investigations and clinic assessment are reported and compared to the prior NAP6 baseline clinic survey.ResultsA total of 266 cases met inclusion criteria between November 2015 and 2016, detailing reactions and investigations. One hundred and ninety‐two of 266 (72%) had anaphylaxis with a trigger identified, of which 140/192 (75%) met NAP6 criteria for IgE‐mediated allergic anaphylaxis, 13% lacking evidence of positive IgE tests were labelled “non‐allergic anaphylaxis”. 3% were non‐IgE‐mediated anaphylaxis. Adherence to guidance was similar to the baseline survey for waiting time for clinic assessment. However, lack of testing for chlorhexidine and latex, non‐harmonized testing practices and poor coverage of all possible culprits was confirmed. Challenge testing may be underused and many have unacceptably delayed assessments, even in urgent cases. Communication or information provision for patients was insufficient, especially for avoidance advice and communication of test results. Insufficient detail regarding skin test methods was available to draw conclusions regarding techniques.Conclusion and Clinical RelevanceCurrent clinical assessment in the UK is effective but harmonization of approach to testing, access to services and MHRA reporting is needed. Expert anaesthetist involvement should increase to optimize diagnostic yield and advice for future anaesthesia. Dynamic tryptase evaluation improves detection of tryptase release where peak tryptase is <14 μg/L and should be adopted. Standardized clinic reports containing appropriate details of tests, conclusions, avoidance, cross‐reactivity and suitable alternatives are required to ensure effective, safe future management options.
Laparoscopic technique of modified extraperitoneal (retrotransversalis) end colostomy for abdominoperineal excision
Authors: Tulina I. A. , Kitsenko Yu. E. , Ubushiev M. N. , Efetov S. K. , Wexner S. D. , Tsarkov P. V. 
Published: May 2018

AbstractAimTo describe the technique of a modified extraperitoneal retrotransversalis end colostomy as part of a laparoscopic abdominoperineal excision (APR).MethodThe colostomy site is preoperatively chosen and used intra‐operatively for a trocar. After the rectum has been mobilized the descending colon is freed. The peritoneal margin is gently grasped and the parietal peritoneum and extraperitoneal together with the transversalis fascia are separated from the transverse abdominal muscle fibres upwards for 3–4 cm aiming at the trocar site to form the extraperitoneal retrotransversalis canal. The stoma site trocar is partially withdrawn and its head is turned laterally until its tip is positioned in the layer between the abdominal wall muscles and underlying transversalis and extraperitoneal fascia together with the parietal peritoneum. The CO2 source can be attached so that the gas helps to separate the layers, after which the colostomy trephine is formed at the site of the trocar, the grasper is inserted to gently deliver the blunt end of the descending colon through the canal and the end colostomy is formed in a usual way.ResultsNo procedure‐specific complications were noted in 39 patients who had laparoscopic APR with extraperitoneal retrotransversalis end colostomy from 2009 to 2016. In 23 patients who survived for 3.7 ± 1.7 years after surgery there were no clinical or CT signs of parastomal hernia or prolapse.ConclusionThis single‐institution retrospective case series demonstrates that laparoscopic extraperitoneal retrotransversalis end colostomy is feasible, safe and effective in preventing parastomal hernias and stomal prolapse.
Nonsteroidal anti‐inflammatory drugs reduce the time to recovery of gut function after elective colorectal surgery: a systematic review and meta‐analysis
Authors: Milne T. G. E. , Jaung R. , O'Grady G. , Bissett I. P. 
Published: May 2018

AbstractAimPostoperative ileus causes significant patient morbidity after abdominal surgery. Some evidence suggests nonsteroidal anti‐inflammatory drugs (NSAIDs) may reduce time to gut recovery, but there has not been a meta‐analysis to assess their efficacy. This systematic review and meta‐analysis aimed to determine the benefit of NSAIDs for recovery of postoperative gut function in patients undergoing elective colorectal surgery.MethodMEDLINE, EMBASE, CENTRAL and reference lists were searched with no date or language restrictions. Randomized controlled trials comparing the use of NSAIDs with placebo in the perioperative or postoperative period were identified. Included studies reported outcomes relevant to gut function: time to pass flatus or stool and time to tolerate an oral diet. The mean difference in time from surgery until passage of flatus, stool and tolerance of diet were meta‐analysed using a random‐effects model in RevMan 5.3.ResultsThis study identified 992 relevant articles. Five randomized controlled trials on patients undergoing elective colorectal surgery met our inclusion criteria and were meta‐analysed. Compared with placebo, NSAIDs significantly improved the time to pass flatus (mean difference −9.44 h, 95% CI: −17.22, −1.65, I2 = 70%, P = 0.02), time to pass stool (mean difference −12.09 h, 95% CI: −17.16, −7.02, I2 = 0%, P < 0.001) and time to tolerate a diet (mean difference −11.95 h, 95% CI: −18.66, −5.24, I2 = 0%, P < 0.001).ConclusionNSAIDs significantly improve time to gut recovery after elective colorectal surgery. Current evidence is not adequate to identify whether selective or nonselective drugs should be recommended. Further high‐power studies using selective drugs are required.
Compensating for an Inattentive Audience
Authors: Craycraft Nicole N. , Brown‐Schmidt Sarah 
Published: May 2018

AbstractThe common ground that conversational partners share is thought to form the basic context for language use. According to the classic view, inferences about common ground, or mutual knowledge, are guided by beliefs about the physical, cognitive, and attentional states of one's communicative partners. Here, we provide a first test of the attention assumption for common ground, the proposal that common ground for a co‐present entity—such as an object or an utterance—can only be formed if a person has evidence that his or her partner has also attended to it. In three experiments, a participant speaker and two partners learned names for novel monster pictures as a group. The speaker was then asked to describe the monsters to each partner separately in a referential communication task. The critical manipulation was the (in)attentiveness of one partner at different points in the study. Analysis of the speaker's referring expressions revealed that speakers assumed their partner shared common ground for the monster names only when that partner exhibited engaged attention as the names were learned. These findings provide key and novel support for the classic proposal that formation of common ground critically depends on assumptions about the attentional state of one's conversational partner.
Outcome following right‐extended split liver transplantation in the recent transplant era: Single‐center analysis of a German transplant center
Authors: Herden Uta , Fischer Lutz , Koch Martina , Li Jun , Achilles Eike‐Gert , Nashan Björn 
Published: May 2018

AbstractIntroductionWhen a sufficiently high‐quality liver is available, classic liver graft splitting is performed. In such cases, a small child receives the left‐lateral split graft, with subsequent transplantation of the right‐extended graft in an adult.MethodsWe analyzed 64 patients who received right‐extended liver grafts from 2007 to 2015, and compared outcomes between cases of external vs in‐house graft splitting.ResultsWe found excellent donor data and comparable recipient characteristics. Cold ischemic time was significantly longer for external (14 ± 2 hours; n = 38) vs internal (12 ± 2 hours; n = 26) liver graft splitting. Compared to the internal splitting group, the external liver graft splitting group showed significantly reduced 1‐ and 5‐year patient survival (100% vs 84%; P = .035) and higher rates of biliary (24% vs 12%) and vascular (8% vs 0%) complications.ConclusionsThe outcomes following right‐extended split LTX are disappointing given the excellent organ quality. External liver graft splitting was associated with worse outcome and surgical complication rates. This may be related to the prolonged cold ischemic time due to twofold transportation, as well as the ignorance of the splitting procedure details and related pitfalls.
Cerebral vasculopathy in childhood neurofibromatosis type 2: cause for concern?
Authors: Lascelles Karine , Afridi Shazia , Siddiqui Ata , Hemingway Cheryl , Ferner Rosalie , Ganesan Vijeya 
Published: May 2018

Unlike adult neurofibromatosis type 2 (NF2), which presents with symptoms related to bilateral vestibular schwannomas, children with NF2 most frequently present with ocular, dermatological, and neurological symptoms. Arteriopathy, a well‐established feature in neurofibromatosis type 1, is not a widely recognized feature of NF2. Here we report three children with NF2 with cerebral arteriopathy and/or arterial ischaemic stroke. Bevacizumab, a vascular endothethial growth factor inhibitor, is an established treatment for rapidly growing vestibular schwannomas; however, it carries a risk of both ischaemic and haemorrhagic stroke. Thus, the role of screening and risk to benefit ratio of bevacizumab in NF2 merit further consideration.What this paper adds

Children with neurofibromatosis type 2 (NF2) may be at increased risk of cerebral vasculopathy and arterial ischaemic stroke.

Targeted magnetic resonance angiography should be performed in children with NF2 who are being considered for bevacizumab therapy.
Characteristics of high‐ and low‐risk individuals in the PRIORITY study: urinary proteomics and mineralocorticoid receptor antagonism for prevention of diabetic nephropathy in Type 2 diabetes
Authors: Tofte N. , Lindhardt M. , Adamova K. , Beige J. , Beulens J. W. J. , Birkenfeld A. L. , Currie G. , Delles C. , Dimos I. , Francová L. , Frimodt‐Møller M. , Girman P. , Göke R. , Havrdova T. , Kooy A. , Mischak H. , Navis G. , Nijpels G. , Noutsou M. , Ortiz A. , Parvanova A. , Persson F. , Ruggenenti P. L. , Rutters F. , Rychlík I. , Spasovski G. , Speeckaert M. , Trillini M. , von der Leyen H. , Rossing P. 
Published: May 2018

AbstractAimTo compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273.MethodsWe conducted a prospective, randomized, double‐blind, placebo‐controlled international multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high‐ or low‐risk groups based on CKD273 score. Clinical baseline data for the whole cohort and stratified by risk groups are reported. The associations between CKD273 and traditional risk factors for diabetic kidney disease were evaluated using univariate and logistic regression analysis.ResultsA total of 1777 participants from 15 centres were included, with 12.3% of these having a high‐risk proteomic pattern. Participants in the high‐risk group (n=218), were more likely to be men, were older, had longer diabetes duration, a lower estimated GFR and a higher urinary albumin:creatinine ratio than those in the low‐risk group (n=1559, P<0.02). Numerical differences were small and univariate regression analyses showed weak associations (R2 < 0.04) of CKD273 with each baseline variable. In a logistic regression model including clinical variables known to be associated with diabetic kidney disease, estimated GFR, gender, log urinary albumin:creatinine ratio and use of renin‐angiotensin system‐blocking agents remained significant determinants of the CKD273 high‐risk group: area under the curve 0.72 (95% CI 0.68–0.75; P<0.01).ConclusionsIn this population of individuals with Type 2 diabetes and normoalbuminuria, traditional diabetic kidney disease risk factors differed slightly between participants at high risk and those at low risk of diabetic kidney disease, based on CKD273. These data suggest that CKD273 may provide additional prognostic information over and above the variables routinely available in the clinic. Testing the added value will be subject to our ongoing study. (European Union Clinical Trials Register: EudraCT 2012‐000452‐34 and Clinicaltrials.gov: NCT02040441).