bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice
Authors: Bo E. , Farinetti A. , Marraudino M. , Sterchele D. , Eva C. , Gotti S. , Panzica G. 
Published: June 2016

SummaryTributyltin (TBT), a pesticide used in antifouling paints, is toxic for aquatic invertebrates. In vertebrates, TBT may act in obesogen‐ inducing adipogenetic gene transcription for adipocyte differentiation. In a previous study, we demonstrated that acute administration of TBT induces c‐fos expression in the arcuate nucleus. Therefore, in this study, we tested the hypothesis that adult exposure to TBT may alter a part of the nervous pathways controlling animal food intake. In particular, we investigated the expression of neuropeptide Y (NPY) immunoreactivity. This neuropeptide forms neural circuits dedicated to food assumption and its action is mediated by Y1 receptors that are widely expressed in the hypothalamic nuclei responsible for the regulation of food intake and energy homeostasis. To this purpose, TBT was orally administered at a dose of 0.025 mg/kg/day/body weight to adult animals [male and female C57BL/6 (Y1‐LacZ transgenic mice] for 4 weeks. No differences were found in body weight and fat deposition, but we observed a significant increase in feed efficiency in TBT‐treated male mice and a significant decrease in circulating leptin in both sexes. Computerized quantitative analysis of NPY immunoreactivity and Y1‐related β‐galactosidase activity demonstrated a statistically significant reduction in NPY and Y1 transgene expression in the hypothalamic circuit controlling food intake of treated male mice in comparison with controls. In conclusion, the present results indicate that adult exposure to TBT is profoundly interfering with the nervous circuits involved in the stimulation of food intake.
Impact of metritis on the generation of reactive oxygen species by circulating phagocytes and plasma lipopolysaccharide concentration in peripartum dairy cows
Authors: Magata Fumie , Morino Ikumi , Teramura Makoto , Tsunoda Ei , Kawashima Chiho , Haneda Shingo , Miyamoto Akio , Kida Katsuya , Shimizu Takashi 
Published: June 2016

AbstractThis study examined the relationship between postpartum metritis, reactive oxygen species (ROS) generation, and plasma lipopolysaccharide (LPS) concentration in peripartum dairy cows. Blood was collected twice weekly from 2 weeks prepartum through 6 weeks postpartum. Whole blood chemiluminescence (WBCL) was measured using the luminol‐enhanced zymosan‐stimulated chemiluminescence assay. Cows were examined for uterine health disorders and classified into two groups, healthy (n = 11) and metritis (n = 5). Metritis had a significant effect on WBCL, with cows with metritis having a higher WBCL. Plasma LPS concentrations in cows with metritis were significantly higher than in healthy cows. To examine the effect of LPS on WBCL, blood was sampled in healthy peripartum cows (1 to 2 weeks prepartum,n = 8; 0 to 3 weeks postpartum,n = 11; and 4 to 8 weeks postpartum,n = 8) and incubated with LPS. At 1 endotoxin units/mL of LPS, similar to the plasma LPS concentration in cows with metritis, the WBCL increased in cows at 0 to 3 weeks postpartum. Results indicate that the increase in ROS generation and plasma LPS concentration are associated with metritis, and LPS may be responsible for enhanced ROS generation in early postpartum dairy cows.
Impact of age on long‐term anticoagulation and how gender and monitoring setting affect it: implications for decision making and patient management
Authors: Abohelaika Salah , Wynne Hilary , Avery Peter , Robinson Brian , Kesteven Patrick , Kamali Farhad 
Published: June 2016

AimsStabilization of anticoagulation control is seminal to reducing the risk of adverse effects of vitamin K antagonists. Reliable information on how ageing influences this is lacking. We set out to assess the true age‐related changes in anticoagulation control, how gender and patient setting influence this, and the possible implications of these for patient outcomes and management.MethodsIn atrial fibrillation (AF) patients of a unified anticoagulant service monitoring patients in general practice or hospital‐based clinics and housebound patients at home, international normalized ratio (INR) and warfarin dose data between 2000 and 2013 were extracted via the DAWN dosing program. Anticoagulation control was assessed by calculating percentage time spent within target INR (TTR).ResultsA total of 2094 AF patients [938 (44.8%) in general practice (GP) and 531 (25.4%) in hospital (H)‐based clinics and 625 (29.8%) through the domiciliary service (D)] were evaluated. The frequency of warfarin dose changes and INR monitoring events declined until about age 67, then increased as patients got older. The TTR according to age was significantly lower and the probability of having a TTR ≤65% according to age was higher for D than for H and GP, and females had a greater probability of having a TTR ≤65% than age‐matched males.ConclusionIdentification of factors underlying poorer anticoagulation control in older housebound patients and the introduction of effective modifications to improve the clinical effectiveness of anticoagulation in such patients is needed.
Do Diuretics have Antinociceptive Actions: Studies of Spironolactone, Eplerenone, Furosemide and Chlorothiazide, Individually and with Oxycodone and Morphine
Authors: Jokinen Viljami , Lilius Tuomas , Laitila Jouko , Niemi Mikko , Kambur Oleg , Kalso Eija , Rauhala Pekka 
Published: June 2016

AbstractSpironolactone, eplerenone, chlorothiazide and furosemide are diuretics that have been suggested to have antinociceptive properties, for example via mineralocorticoid receptor antagonism. In co‐administration, diuretics might enhance the antinociceptive effect of opioids via pharmacodynamic and pharmacokinetic mechanisms. Effects of spironolactone (100 mg/kg, i.p.), eplerenone (100 mg/kg, i.p.), chlorothiazide (50 mg/kg, i.p.) and furosemide (100 mg/kg, i.p.) were studied on acute oxycodone (0.75 mg/kg, s.c.)‐ and morphine (3 mg/kg, s.c.)‐induced antinociception using tail‐flick and hot plate tests in male Sprague Dawley rats. The diuretics were administered 30 min. before the opioids, and behavioural tests were performed 30 and 90 min. after the opioids. Concentrations of oxycodone, morphine and their major metabolites in plasma and brain were quantified by mass spectrometry. In the hot plate test at 30 and 90 min., spironolactone significantly enhanced the antinociceptive effect (% of maximum possible effect) of oxycodone from 10% to 78% and from 0% to 50%, respectively, and that of morphine from 12% to 73% and from 4% to 83%, respectively. The brain oxycodone and morphine concentrations were significantly increased at 30 min. (oxycodone, 46%) and at 90 min. (morphine, 190%). We did not detect any independent antinociceptive effects with the diuretics. Eplerenone and chlorothiazide did not enhance the antinociceptive effect of either opioid. The results suggest that spironolactone enhances the antinociceptive effect of both oxycodone and morphine by increasing their concentrations in the central nervous system.
What is standard care for people with learning disabilities and behaviour that challenges and what does it cost?
Authors: Iemmi Valentina , Knapp Martin , Gore Nick , Cooper Vivien , Brown Freddy Jackson , Reid Caroline , Saville Maria ,   BC Delphi Group
Published: June 2016

Accessible summary

The provision of care and support for people with learning disabilities and behaviour that challenges in England is mixed.

Children and young people with learning disabilities and behaviour that challenges are likely to live within the community, while adults will be in residential care.

Overall, supporting people with learning disabilities and behaviour that challenges within the community is likely to be less expensive than supporting them in residential care.

AbstractBackground: We describe current care arrangements in England for children, young people and adults with learning disabilities and behaviour that challenges, and estimate their comparative costs.Materials and Methods: A two‐round Delphi exercise was performed in March and April 2014, followed by a costing exercise.Results: The study finds a mixed picture: participants reported that 60–87% of children, 66–88% of young people and 34–47% of adults were likely to be living within the community. Annual cost of care would range between £39 612 and £74 876 for children, between £35 235 and £52 832 for young people and between £81 478 and £94 799 for adults.Conclusion: While residential‐based care may continue to be necessary for respite or for individuals with particular needs, community‐based care may be an economically attractive alternative, supporting the inclusion of people with learning disabilities and behaviour that challenges within their communities, potentially at a lower cost.
Systemic associations of corneal deposits: a review and photographic guide
Authors: Patel Dipika V 
Published: June 2016

AbstractThe cornea may be considered ‘the window to the body’, with numerous systemic diseases exhibiting corneal manifestations. Indeed, the cornea is often the presenting sign of such diseases. This article provides a concise review and photographic guide to a range of types of corneal deposition that may be observed secondary to systemic disease.
The treatment of all MRI‐defined low rectal cancers in a single expert centre over a 5‐year period: is there room for improvement?
Authors: Kusters M. , Slater A. , Betts M. , Hompes R. , Guy R. J. , Jones O. M. , George B. D. , Lindsey I. , Mortensen N. J. , James D. R. , Cunningham C. 
Published: June 2016

AbstractAimOutcomes following treatment for low rectal cancer still remain inferior to those for upper rectal cancer. A clear definition of ‘low’ rectal cancer is lacking and consensus is more likely using a definition based on MRI criteria. This study aimed to determine disease presentation and treatment outcome of low rectal cancer based on a strict anatomical definition.MethodA low rectal cancer was defined as one with a lower border below the pelvic attachment of the levator muscles on sagittal MRI. One hundred and eighty consecutive patients with tumours defined by this criterion between 2006 and 2011 were identified from a prospectively managed departmental database.ResultsOne hundred and eighteen patients (66%) underwent curative resection and 12 (7%) palliative resection. Eleven patients (6%) were entered into a ‘watch and wait’ (W&W) protocol; 10 others (5%) were not fit to undergo any operation. Some 26 patients (14%) had nonresectable local or metastatic disease. An R0 resection was the most important factor influencing survival after curative surgery. R+ resections occurred in 12% of non‐abdominoperineal excisions, 11% of abdominoperineal excisions and 47% of extended resections. Overall survival was similar in the curative resections compared with the W&W patients. In 23 of the 96 (24%) treated with neoadjuvant chemoradiotherapy there was a persistent clinical or a pathological complete response.ConclusionIn curative resections, a clear margin is the most important determinant of survival. In 24% of the patients treated with neoadjuvant chemoradiotherapy, surgery could potentially have been avoided. There is scope for improvement in the treatment of locally advanced rectal cancers.
Commonly used reference values underestimate oxygen uptake in healthy, 50‐year‐old Swedish women
Authors: Genberg M. , Andrén B. , Lind L. , Hedenström H. , Malinovschi A. 
Published: June 2016

SummaryCardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (VO2) and CO2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared VO2 at maximal load (peakVO2) and anaerobic threshold (VO2@AT) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakVO2 with regard to peak RER and BR. In all, 181 healthy, 50‐year‐old individuals (91 women) performed CPET. PeakVO2 was best predicted using Jones et al. (100·5%). Furthermore, underestimation of peakVO2 in women was found for all studied reference values (P<0·001) and was largest for Hansen‐Wasserman: women had 115% of predicted peakVO2, while men had 103%. PeakVO2 was similar in subjects with peak RER of 1–1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min−1, P = 0·11). Lower BR (≤30%) related to significantly higher peakVO2 (P<0·001). In conclusion, peakVO2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals.
Pregnancy in cardiac transplant recipients
Authors: Bhagra Catriona J. , Bhagra Sai K. , Donado Alicia , Butt Tanveer , Forrest Lindsey , MacGowan Guy A. , Parry Gareth 
Published: June 2016

AbstractPurposeSuccessful pregnancy following cardiac transplantation has been described, although outcome data from individual centers are relatively sparse. We investigated maternal and fetal outcomes including change in left ventricular (LV) function and calcineurin inhibitor (CNI) dose in women who became pregnant from our institution.MethodsWe identified every female patient <49 years at the time of transplant who survived >3 months post‐surgery, between 1985 and 2014. Those who conceived had a review of their medical records and transplant charts. Those currently alive were interviewed.ResultsThere were 22 pregnancies in 17 women with 20 live births (91%). Mean time from transplantation was 98±62.4 months. Rejection complicated one pregnancy, and LV function remained normal in all others. Hypertension complicated 3 (13.6%), preeclampsia 3 (13.6%), and cholestasis 1 (4.5%). Mean birthweight was 2447±608 grams at 34.1±3.6 weeks. Four women died following pregnancy. A significant increase in total daily dose of tacrolimus and cyclosporine A was required to maintain therapeutic levels through pregnancy (CyA, P<.001; and Tac, P=.001), with no deterioration in serum creatinine.ConclusionsWe report a 91% live birth rate post‐cardiac transplantation. Meticulous individualized care with frequent monitoring of CNI levels and LV function is necessary to optimize the maternal and fetal outcomes.
The clinical relevance of Organ Procurement and Transplantation Network screening criteria for program performance review in the United States
Authors: Salkowski Nicholas , Wey Andrew , Snyder Jon J. , Orlowski Jeffrey P. , Israni Ajay K. , Kasiske Bertram L. 
Published: June 2016

AbstractThe Organ Procurement and Transplantation Network is charged with overseeing the quality of transplant programs in the United States. However, there has been controversy over whether too many programs are being identified as underperforming. It has also been suggested that dramatic improvements in outcomes throughout the United States have made the thresholds for determining which deceased donor transplant programs are underperforming no longer clinically relevant. The Scientific Registry of Transplant Recipients compared actual and expected 1‐y graft survival for transplant programs identified as underperforming in the most recent cohort (transplants from July 1, 2012 to December 31, 2014). For most organs, actual 1‐y graft survival was substantially lower for programs identified as underperforming than for programs identified as performing as expected. Differences were smallest for kidney programs: median 1‐y graft survival 89.2% vs 95.4% in large‐volume programs identified and not identified for Membership and Professional Standards Committee review, respectively. Median expected graft survival was only slightly lower (94.8% vs 95.1%, respectively), suggesting that identified and not identified programs tend to have similar risk tolerances. An excess of 143 grafts were lost from kidney programs identified as underperforming. Transplant programs identified as underperforming generally have reduced 1‐y graft survival that stakeholders may consider clinically relevant.
CYP3A pharmacogenetics and tacrolimus disposition in adult heart transplant recipients
Authors: Deininger Kimberly M. , Vu Anh , Page Robert L. , Ambardekar Amrut V. , Lindenfeld JoAnn , Aquilante Christina L. 
Published: June 2016

AbstractBackgroundCytochrome P450 (CYP) 3A polymorphisms are associated with variable CYP3A metabolizing enzyme activity and tacrolimus pharmacokinetics. We sought to determine the singular and combined impact of CYP3A4*22 and CYP3A5*3 variants on tacrolimus drug disposition in adult heart transplant recipients.MethodsThe retrospective study included 76 patients greater than one year post‐heart transplant and receiving tacrolimus. Patients were genotyped for CYP3A4*22 and CYP3A5*3, and combined genotypes were classified as follows: extensive metabolizers (EM, CYP3A4*1/*1+CYP3A5*1 carriers), intermediate metabolizers (IM, CYP3A4*1/*1+CYP3A5*3/*3, or CYP3A4*22 carriers+CYP3A5*1 carriers), and poor metabolizers (PM, CYP3A4*22 carriers+CYP3A5*3/*3). The primary outcome was tacrolimus dose‐adjusted trough concentration (C0/D, ng/mL per mg/d).ResultsIn singular analysis, tacrolimus C0/D did not differ significantly between CYP3A4*22 genotype groups. However, tacrolimus C0/D was 1.8‐fold lower (P<.001) in CYP3A5 expressers vs non‐expressers. When combined CYP3A genotypes were evaluated, tacrolimus C0/D was 1.8‐fold lower in EMs vs IMs (P<.001) and EMs vs PMs (P=.001). Tacrolimus C0/D did not differ significantly between CYP3A IMs vs PMs.ConclusionCombined CYP3A genotype was associated with tacrolimus drug disposition in adult heart transplant recipients, but the effect was largely driven by CYP3A5*3. These data suggest that CYP3A4*22 and combined CYP3A genotypes are unlikely to provide additional information beyond CYP3A5 genotype.
Hip health at skeletal maturity: a population‐based study of young adults with cerebral palsy
Authors: Wawrzuta Joanna , Willoughby Kate L , Molesworth Charlotte , Ang Soon Ghee , Shore Benjamin J , Thomason Pam , Graham H Kerr 
Published: June 2016

AimWe studied ‘hip health’ in a population‐based cohort of adolescents and young adults with cerebral palsy to investigate associations between hip morphology, pain, and gross motor function.MethodNinety‐eight young adults (65 males, 33 females) from the birth cohort were identified as having developed hip displacement (migration percentage >30) and were reviewed at a mean age of 18 years 10 months (range 15–24y). Hip morphology was classified using the Melbourne Cerebral Palsy Hip Classification Scale (MCPHCS). Severity and frequency of pain were recorded using Likert scales. Gross motor function was classified by the Gross Motor Function Classification System (GMFCS).ResultsHip pain was reported in 72% of participants. Associations were found between pain scores and both hip morphology and GMFCS. Median pain severity score for MCPHCS grades 1 to 4 was 2 (interquartile range [IQR] 1.0–3.0) compared to 7 (IQR 6.0–8.0) for grades 5 and 6 (severe subluxation or dislocation). Hip surveillance and access to surgery were associated with improved hip morphology and less pain.InterpretationPoor hip morphology at skeletal maturity was associated with high levels of pain. Limited hip surveillance and access to surgery, rather than GMFCS, was associated with poor hip morphology. The majority of young adults who had access to hip surveillance, and preventive and reconstructive surgery, had satisfactory hip morphology at skeletal maturity and less pain.
Difference in the Prognostic Impact of Left Ventricular Global Longitudinal Strain between Anterior and Nonanterior Myocardial Infarction
Authors: Jang Se Yong , Yang Dong Heon , Kim Nam Kyun , Kim Chang‐Yeon , Bae Myung Hwan , Lee Jang Hoon , Park Hun Sik , Cho Yongkeun , Chae Shung Chull 
Published: June 2016

BackgroundSpeckle tracking–derived global longitudinal strain (GLS) of left ventricle is a potent prognostic marker for patients with ST‐segment elevation myocardial infarction (STEMI). The purpose of this study was to investigate the difference of prognostic impact of GLS between anterior and nonanterior myocardial infarction.MethodsThis study included 686 patients who underwent primary percutaneous coronary intervention for their first STEMI between November 2007 and April 2012. Differences in the prognostic impact of GLS between anterior MI group and nonanterior MI group were evaluated. The composite of all‐cause mortality and hospitalization for heart failure in 2 years was investigated for outcome.ResultsDuring the follow‐up period, 77 (11.2%) adverse events occurred. The anterior and nonanterior MI groups included 339 and 347 patients, respectively. Among patients with anterior MI, GLS significantly predicted 2‐year outcome in an adjusted model (adjusted hazard ratio [HR] 1.186; 95% confidence interval [CI] 1.071–1.314, P = 0.001), whereas the association between GLS and mortality was weaker in the nonanterior MI group (adjusted HR 0.977; 95% CI 0.884–1.081, P = 0.657). The interaction between the infarction territory and GLS was significant (P for interaction = 0.018), indicating that GLS was a more sensitive predictor of mortality in patients with anterior MI than that in those with nonanterior MI.ConclusionsSpeckle tracking–derived GLS of left ventricle more sensitively predicted clinical outcome in patients with anterior MI than in those with nonanterior MI.
Moderated online social therapy for depression relapse prevention in young people: pilot study of a ‘next generation’ online intervention
Authors: Rice Simon , Gleeson John , Davey Christopher , Hetrick Sarah , Parker Alexandra , Lederman Reeva , Wadley Greg , Murray Greg , Herrman Helen , Chambers Richard , Russon Penni , Miles Christopher , D'Alfonso Simon , Thurley Melissa , Chinnery Gina , Gilbertson Tamsyn , Eleftheriadis Dina , Barlow Emma , Cagliarini Daniella , Toh Jia‐Wern , McAlpine Stuart , Koval Peter , Bendall Sarah , Jansen Jens Einar , Hamilton Matthew , McGorry Patrick , Alvarez‐Jimenez Mario 
Published: June 2016

AbstractAimImplementation of targeted e‐mental health interventions offers a promising solution to reducing the burden of disease associated with youth depression. A single‐group pilot study was conducted to evaluate the acceptability, feasibility, usability and safety of a novel, moderated online social therapy intervention (entitled Rebound) for depression relapse prevention in young people.MethodsParticipants were 42 young people (15–25 years) (50% men; mean age = 18.5 years) in partial or full remission. Participants had access to the Rebound platform for at least 12 weeks, including the social networking, peer and clinical moderator and therapy components.ResultsFollow‐up data were available for 39 (92.9%) participants. There was high system usage, with 3034 user logins (mean = 72.2 per user) and 2146 posts (mean = 51.1). Almost 70% of users had ≥10 logins over the 12 weeks, with 78.5% logging in over at least 2 months of the pilot. A total of 32 (84%) participants rated the intervention as helpful. There was significant improvement between the number of participants in full remission at baseline (n = 5; none of whom relapsed) relative to n = 19 at 12‐week follow‐up (P < 0.001). Six (14.3%) participants relapsed to full threshold symptoms at 12 weeks. There was a significant improvement to interviewer‐rated depression scores (Montgomery–Asberg Depression Rating Scale (MADRS); P = 0.014, d = 0.45) and a trend for improved strength use (P = 0.088, d = 0.29). The single‐group design and 12‐week treatment phase preclude a full understanding of the clinical benefits of the Rebound intervention.ConclusionsThe Rebound intervention was shown to be acceptable, feasible, highly usable and safe in young people with major depression.