bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Wide‐awake drunkenness’? Investigating the association between alcohol intoxication and stimulant use in the night‐time economy
Authors: Pennay Amy , Miller Peter , Busija Lucy , Jenkinson Rebecca , Droste Nicolas , Quinn Brendan , Jones Sandra C. , Lubman Dan I. 
Published: September 2014

AbstractAimsWe tested whether patrons of the night‐time economy who had co‐consumed energy drinks or illicit stimulants with alcohol had higher blood alcohol concentration (BAC) levels than patrons who had consumed only alcohol.DesignStreet intercept surveys (n = 4227) were undertaken between 9 p.m. and 5 a.m. over a period of 7 months.SettingInterviews were undertaken with patrons walking through entertainment precincts, queuing to enter venues or exiting venues in five Australian cities.ParticipantsThe response rate was 92.1%; more than half the study sample was male (60.2%) and the median age was 23 years (range 18–72).MeasurementsData were collected on demographics, length of drinking session, venue types visited, types and quantity of alcohol consumed and other substance use. A BAC reading was recorded and a subsample of participants was tested for other drug use.FindingsCompared with the total sample (0.068%), illicit stimulant consumers (0.080%; P = 0.004) and energy drink consumers (0.074%; P < 0.001) had a significantly higher median BAC reading, and were more likely to engage in pre‐drinking (65.6, 82.1 and 77.6%, respectively, P < 0.001) and longer drinking sessions (4, 5 and 4.5 hours, respectively, P < 0.001). However, stimulant use was not associated independently with higher BAC in the final multivariable model (illicit stimulants P = 0.198; energy drinks P = 0.112). Interaction analyses showed that stimulant users had a higher BAC in the initial stages of the drinking session, but not after 4–6 hours.ConclusionsWhile stimulant use does not predict BAC in and of itself, stimulants users are more likely to engage in prolonged sessions of heavy alcohol consumption and a range of risk‐taking behaviours on a night out, which may explain higher levels of BAC among stimulants users, at least in the initial stages of the drinking session.
Impact of fetal and neonatal environment on beta cell function and development of diabetes
Authors: Nielsen Jens H. , Haase Tobias N. , Jaksch Caroline , Nalla Amarnadh , Søstrup Birgitte , Nalla Anjana A. , Larsen Louise , Rasmussen Morten , Dalgaard Louise T. , Gaarn Louise W. , Thams Peter , Kofod Hans , Billestrup Nils 
Published: September 2014

AbstractThe global epidemic of diabetes is a serious threat against health and healthcare expenses. Although genetics is important it does not explain the dramatic increase in incidence, which must involve environmental factors. Two decades ago the concept of the thrifty phenotype was introduced, stating that the intrauterine environment during pregnancy has an impact on the gene expression that may persist until adulthood and cause metabolic diseases like obesity and type 2 diabetes. As the pancreatic beta cells are crucial in the regulation of metabolism this article will describe the influence of normal pregnancy on the beta cells in both the mother and the fetus and how various conditions like diabetes, obesity, overnutrition and undernutrition during and after pregnancy may influence the ability of the offspring to adapt to changes in insulin demand later in life. The influence of environmental factors including nutrients and gut microbiota on appetite regulation, mitochondrial activity and the immune system that may affect beta cell growth and function directly and indirectly is discussed. The possible role of epigenetic changes in the transgenerational transmission of the adverse programming may be the most threatening aspect with regard to the global diabetes epidemics. Finally, some suggestions for intervention are presented.
Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy
Authors: Nalla Amarnadh , Ringholm Lene , Søstrup Brigitte , Højrup Peter , Thim Lars , Levery Steven B. , Vakhrushev Sergey Y. , Billestrup Nils , Mathiesen Elisabeth R. , Damm Peter , Nielsen Jens H. 
Published: September 2014

AbstractObjectiveSeveral studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy‐associated circulating beta cell growth factors.SamplesSerum samples from nonpregnant and pregnant women.MethodsThe effect of serum from pregnant women on the proliferation of rat beta cells was studied using [3H]thymidine incorporation and 5‐ethynyl‐2′‐deoxyuridine proliferation assays. In addition, serum from pregnant and nonpregnant women was fractionated by gel filtration and high performance liquid chromatography. The fractionated serum was screened for mitogenic activity in INS‐1E cells. Proteins and peptides in mitogenic active serum fractions were identified by amino acid sequencing and mass spectrometry.Main outcome measuresPresence of circulating beta cell proliferating factors.ResultsLate gestational pregnancy serum significantly increased proliferation of rat beta cells compared with early pregnancy and nonpregnancy. The mitogenic active serum fractions contained proteins and peptides derived from kininogen‐1, fibrinogen‐α, α1‐antitrypsin, apolipoprotein‐A1, placental lactogen, angiotensinogen and serum albumin.ConclusionPregnancy serum is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.
Blood sampling via a peripheral artery catheter decreases cerebral oxygenation index in very low‐birthweight infants
Authors: Mehler Katrin , Nowak Mareike , Oberthuer André , Hahn Moritz , Roth Bernhard , Kribs Angela 
Published: September 2014

AbstractAimThis study evaluated the impact of blood sampling via peripheral arterial catheters on cerebral oxygenation and blood volume as a function of blood sampling velocity.MethodsNear‐infrared spectroscopy was applied to 20 very low‐birthweight infants during peripheral arterial blood sampling. Changes in cerebral oxygenated, deoxygenated and total haemoglobin, cerebral blood volume and cerebral oxygenation index were recorded. Heart rate and oxygen saturation were measured continuously. To assess the impact of blood sampling velocity, both fast 40‐sec and slow 70‐sec sampling procedures were performed in a crossover study design, in which the order of sampling velocities was randomised for each patient.ResultsBoth fast and slow blood sampling procedures resulted in a significant decrease in cerebral oxygenation index (fast, p = 0.002, slow, p = 0.008), and an increase in mean heart rate (both p = 0.02) and mean blood pressure (p = 0.02 and 0.04). Oxygenated and total haemoglobin and cerebral blood volume only decreased significantly after slow blood sampling (p < 0.001).ConclusionBlood sampling from peripheral arterial catheters leads to significant fluctuations in cerebral oxygenation independent of the sampling velocity. Changes are comparable to those reported from umbilical blood sampling. We advise that blood sampling should be restricted as much as possible.
A Comparison of the Reactivating and Therapeutic Efficacy of Two Newly Developed Oximes (K727 and K733) with Oxime K203 and Trimedoxime in Tabun‐Poisoned Rats and Mice
Authors: Kassa Jiri , Sepsova Vendula , Tumova Martina , Horova Anna , Musilek Kamil 
Published: September 2014

AbstractThe reactivating and therapeutic efficacy of three original bispyridinium oximes (K727, K733 and K203) and one currently available oxime (trimedoxime) was evaluated in tabun‐poisoned rats and mice. The oxime‐induced reactivation of tabun‐inhibited acetylcholinesterase was measured in diaphragm and brain of tabun‐poisoned rats. The results showed that the reactivating efficacy of two recently developed oximes (K727 and K733) does not achieve the level of the reactivation of tabun‐inhibited acetylcholinesterase induced by oxime K203 and trimedoxime. While all oximes studied were able to increase the activity of tabun‐inhibited acetylcholinesterase in diaphragm, oxime K733 was not able to reactivate tabun‐inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied roughly corresponds to their reactivating efficacy. While both recently developed oximes were able to reduce acute toxicity of tabun less than 1.5‐fold, another original oxime K203 and commonly used trimedoxime reduced the acute toxicity of tabun almost two times. In conclusion, the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of oxime K203 and trimedoxime, and therefore, they are not suitable for their replacement of commonly used oximes for the antidotal treatment of acute tabun poisoning.
Pre‐systemic Elimination of Tilidine: Localization and Consequences for the Formation of the Active Metabolite Nortilidine
Authors: Eichbaum Christine , Mathes Kristin , Burhenne Jürgen , Markert Christoph , Blank Antje , Mikus Gerd 
Published: September 2014

AbstractThe therapeutic activity of tilidine, an opioid analgesic, is mainly related to its active metabolite nortilidine. Nortilidine formation mainly occurs during the high intestinal first‐pass metabolism of tilidine by N‐demethylation. Elimination of the active nortilidine to the inactive bisnortilidine is also mediated by N‐demethylation and is supposed to take place in the liver, probably at a smaller rate. The aim of this study was the investigation of the pre‐systemic elimination of tilidine using grapefruit juice (GFJ) as an intestinal CYP3A4 inhibitor and efavirenz (EFV) as a CYP3A4 activator. A randomized, open, placebo‐controlled, cross‐over study was conducted in 12 healthy volunteers using 100 mg tilidine solution p.o., regular strength GFJ 250 mL (3 times at 12‐hr intervals) and EFV 400 mg (12 hr before tilidine administration). Tilidine, nortilidine and bisnortilidine in plasma and urine were quantified by a validated LC/MS/MS analysis. GFJ did not change any pharmacokinetic parameter of tilidine and its metabolites, which suggests that intestinal CYP3A4 does not contribute to the first‐pass metabolism of tilidine. No effect of EFV on the pharmacokinetics of the active nortilidine was observed except a significant reduction of the terminal elimination half‐life by 15%. Overall elimination (renal and metabolic clearances) was unaffected by every treatment. CYP3A4 does not seem to play a major role in tilidine first‐pass and overall metabolism. Other unknown metabolites and their enzymes responsible for their formation have to be investigated as they account for the majority of renally excreted metabolites.
Effect of erythropoietin on hepatic cytochrome P450 expression and function in an adenine‐fed rat model of chronic kidney disease
Authors: Feere D A , Velenosi T J , Urquhart B L 
Published: September 2014

Background and PurposeErythropoietin (EPO) is used to treat anaemia associated with chronic kidney disease (CKD). Hypoxia is associated with anaemia and is known to cause a decrease in cytochrome P450 (P450) expression. As EPO production is regulated by hypoxia, we investigated the role of EPO on P450 expression and function.Experimental ApproachMale Wistar rats were subjected to a 0.7% adenine diet for 4 weeks to induce CKD. The diet continued for an additional 2 weeks while rats received EPO by i.p. injection every other day. Following euthanasia, hepatic P450 mRNA and protein expression were determined. Hepatic enzyme activity of selected P450s was determined and chromatin immunoprecipitation was used to characterize binding of nuclear receptors involved in the transcriptional regulation of CYP2C and CYP3A.Key ResultsEPO administration decreased hepatic mRNA and protein expression of CYP3A2 (P < 0.05), but not CYP2C11. Similarly, EPO administration decreased CYP3A2 protein expression by 81% (P < 0.001). A 32% decrease (P < 0.05) in hepatic CYP3A enzymatic activity (Vmax) was observed for the formation of 6βOH‐testosterone in the EPO‐treated group. Decreases in RNA pol II recruitment (P < 0.01), hepatocyte nuclear factor 4α binding (P < 0.05) and pregnane X receptor binding (P < 0.01) to the promoter region of CYP3A were also observed in EPO‐treated rats.Conclusions and ImplicationsOur data show that EPO decreases the expression and function of CYP3A, but not CYP2C in rat liver.
The Common Assessment Framework: the impact of the lead professional on families and professionals as part of a continuum of care in England
Authors: Holmes Lisa , McDermid Samantha 
Published: September 2014

AbstractThis paper utilizes data gathered as part of an exploratory study to assess the costs and impact of the Common Assessment Framework (CAF), to examine the impact that the lead professional role had on families and workers. The study found that both families and workers believed the lead professional to be central to the CAF process, providing a range of support, coordinating multi‐agency responses to need and acting as a single point of contact between families and workers. The paper highlights the need for consideration to be given to inter‐agency working, data sharing, training for workers and the capacity implications for those taking on the role. The extent to which the lead professional might be more integrated into the continuum of support for vulnerable children and families is also examined. The paper highlights the need to consider the lead professional's role in not only preventing the need for more intensive services, such as those provided by statutory social work, but also maintaining outcomes achieved once a child protection plan is closed, or a child is reunified with his or her birth family after a period of being in care. The implications of the findings for policy and practice are discussed.
Bone healing at bicortically installed implants with different surface configurations. An experimental study in rabbits
Authors: Caneva Marco , Lang Niklaus P. , Calvo Guirado José Luis , Spriano Silvia , Iezzi Giovanna , Botticelli Daniele 
Published: September 2014

AbstractObjectiveTo study the sequential healing at bicortically installed implants with surface modifications by the use of fluoroboric acid and/or H2O2.Material and methodsTwenty‐eight albino New Zealand rabbits were used. Two recipient sites were prepared in the tibiae bilaterally, one in the metaphysis and the second in the diaphysis regions. Four implants with different surface characteristics were randomly installed with bicortical stabilization: (i) sandblasted and acid‐etched; (ii) same surface as i, but with a substitution of the hydrofluoric acid with fluoroboric acid; (iii) same surface as i, additionally treated with H2O2; and (iv) same surface modified as ii, additionally treated with H2O2. The animals were killed after 5, 8, 15, and 30 days. Ground sections were prepared for histological analyses.ResultsNo statistically significant differences in osseointegration were found among various surfaces at any of the healing periods. A higher degree of osseointegration was observed at the implants placed in the metaphysis compared to those placed in the diaphysis, especially during early healing. A higher degree of osseointegration was found at sites with proximity to compact (cortical) bone when compared to the middle portion of the implants, especially in the diaphysis region.ConclusionsSurfaces modified with different acids or H2O2 resulted in similar osseointegration compared to a standard sandblasted and acid‐etched surface. The portion of the bicortically installed implants in close contact with the cortical compartment presented a higher percentage of osseointegration compared with the region in contact with the bone marrow compartment.
Variants of the melanocortin‐1 receptor: do they matter clinically?
Authors: Haddadeen Ciara , Lai Chester , Cho Shin‐Young , Healy Eugene 
Published: September 2014

AbstractThe melanocortin 1 receptor (MC1R) gene encodes for a seven‐pass transmembrane receptor primarily expressed on melanocytes and melanoma cells. Single nucleotide polymorphisms (SNPs, also termed variants) in MC1R frequently cause red hair, fair skin and are associated with melanoma and keratinocyte‐derived skin cancer development. Activation of wild‐type (WT) MC1R in skin assists cutaneous photoprotection whereas reduced MC1R signalling, seen with MC1R variants, impairs ultraviolet radiation (UVR)‐protective responses. As ancestral humans migrated out of Africa, the evolutionary advantage of MC1R variants may have related to improved cutaneous vitamin D synthesis and higher birthweight reported with certain MC1R variants. Reduced photoprotection secondary to MC1R dysfunction involves pigmentary and non‐pigmentary mechanisms (reduced DNA repair, effects on cell proliferation and possibly immunological parameters), leading to clonal expansion of mutated cells within skin and subsequent carcinogenesis. Recent investigations suggest an association between MC1R genotype and vitiligo, with preliminary evidence that a MC1R agonist, [Nle4‐D‐Phe7]‐alpha‐MSH, in combination with UVB, assists repigmentation. Future development of compounds to correct defective MC1R responses secondary to MC1R variants could result in photoprotective benefits for fair‐skinned individuals and reduce their skin cancer risk.
Sustained translational repression of lactate dehydrogenase 1 in Toxoplasma gondii bradyzoites is conferred by a small regulatory RNA hairpin
Authors: Holmes Michael , Itaas Vaunell , Ananvoranich Sirinart 
Published: September 2014

In response to environmental stresses, Toxoplasma gondii induces a global translational repression which allows for the remodeling of its transcriptome. While some transcripts are preferentially translated, another subset is translationally repressed and maintained in bradyzoites. Although little is known of how transcripts are targeted for sustained translational repression, the targeting probably operates through an RNA‐centric mechanism relying on the recognition of cis‐acting elements. In this study, we sought to determine if the targeting of transcripts through recognizable cis‐acting elements could be responsible for the transcript‐specific sustained translational repression displayed by Toxoplasma bradyzoites. We examined the UTRs of a translationally repressed gene, lactate dehydrogenase 1, and found a 40 nucleotide regulatory element in its 5′UTR. This element specifically induces translational repression in otherwise constitutively expressed transcripts. Mutational studies revealed that the formation of a small 16 nucleotide regulatory RNA hairpin is essential for this activity. We suggest that this hairpin may act as the nucleation site for the binding of an as yet to be identified trans‐acting factor that allows for the transcript to be targeted for translational repression removal from the active translational pool. To our knowledge, this is the first report characterizing a specific cis‐acting element contributing to post‐transcriptional gene regulation in Toxoplasma and suggests the presence of a pathway by which the parasites can recognize, identify and specifically target transcripts for sustained translational repression under stressful conditions.
Autoantibody status and histological variables influence biochemical response to treatment and long‐term outcomes in Japanese patients with primary biliary cirrhosis
Authors: Nakamura Minoru , Kondo Hisayoshi , Tanaka Atsushi , Komori Atsumasa , Ito Masahiro , Yamamoto Kazuhide , Ohira Hiromasa , Zeniya Mikio , Hashimoto Etsuko , Honda Masao , Kaneko Shuichi , Ueno Yoshiyuki , Kikuchi Kentaro , Shimoda Shinji , Harada Kenichi , Arai Kuniaki , Miyake Yasuhiro , Abe Masanori , Taniai Makiko , Saibara Toshiji , Sakisaka Shotaro , Takikawa Hajime , Onji Morikazu , Tsubouchi Hirohito , Nakanuma Yasuni , Ishibashi Hiromi 
Published: September 2014

AimThe aim of the present study is to evaluate the factors influencing biochemical response to treatment and the value of biochemical response for predicting long‐term outcomes in Japanese patients with primary biliary cirrhosis (PBC).MethodsBiochemical response to ursodeoxycholic acid (UDCA) or UDCA plus bezafibrate was defined as good (≤upper limit of normal [ULN]), fair (≤1.5 × ULN) or poor (>1.5 × ULN) at 2 years after initiation of UDCA treatment. Associations between various factors (including age, sex, autoantibody status and histological variables at baseline), biochemical response to treatment and long‐term outcomes were evaluated in 164 Japanese PBC patients.ResultsAnti‐gp210 positivity and a higher bile duct loss score were significant risk factors for worse alkaline phosphatase (ALP) response (odds ratios [OR], 2.78 and 1.85, respectively). Age, anti‐gp210 positivity and anticentromere positivity were significant risk factors for worse alanine aminotransferase (ALT) response (OR, 1.05, 4.0 and 2.77, respectively). Anti‐gp210 positivity and a higher hepatitis score were significant risk factors for worse immunoglobulin (Ig)M response (OR, 2.10 and 2.06, respectively). Worse ALP and IgM response were significant risk factors for progression to late‐stage disease without jaundice (OR, 2.27 and 2.32, respectively). Worse ALT response was a significant risk factor for progression to late‐stage disease with persistent jaundice (OR, 11.11).ConclusionBiochemical response to treatment at 2 years, which is influenced by autoantibody status and histological variables at baseline, can predict long‐term outcomes in Japanese patients with PBC.
Beyond Compartmentalized Atlantics: A Case for Embracing the Atlantic from Spanish American Shores
Authors: Bassi Ernesto 
Published: September 2014

AbstractDespite the recent surge of Atlantic histories that pursue connections across political boundaries, compartmentalized Atlantics still dominate the field's historiographical map. This paper presents some of the most recent efforts to construct Atlantic histories that cut across political borders and depict the entangled nature of lived experiences in the early modern Atlantic world. In particular, focusing on recent works that look at islands as loci of entanglement and studies that follow individuals as they crossed political borders, this article suggests that historians of Spanish America should embrace the Atlantic as a way to contribute to the production of an Atlantic history that more faithfully represents the lived experiences and collective imaginaries of Atlantic dwellers.
The History of Madness and Mental Illness in the Middle Ages: Directions and Questions
Authors: Craig Leigh Ann 
Published: September 2014

AbstractThis article explores the extent of recent publications on the history of madness and mental illness in the Middle Ages. It also argues that as this work continues, the categorical groupings of “madness” and “mental illness” deserve our close scrutiny. An exploration of both medieval and present‐day categorical assumptions reveals the ways in which they shape our reading of medieval texts, of historical causation, and of social agency.