bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain 5‐lipoxygenase over‐expression worsens memory, synaptic integrity, and tau pathology in the P301S mice
Authors: Vagnozzi Alana N. , Giannopoulos Phillip F. , Praticò Domenico 
Published: November 2017

SummaryProgressive accumulation of highly phosphorylated tau protein isoforms is the main feature of a group of neurodegenerative diseases collectively called tauopathies. Data from human and animal models of these diseases have shown that neuroinflammation often accompanies their pathogenesis. The 5‐lipoxygenase (5LO) is an enzyme widely expressed in the brain and a source of potent pro‐inflammatory mediators, while its pharmacological inhibition modulates the phenotype of a tau transgenic mouse model, the htau mice. By employing an adeno‐associated viral vector system to over‐express 5LO in the brain, we examined its contribution to the behavioral deficits and neuropathology in a different transgenic mouse model of tauopathy, the P301S mouse line. Compared with controls, 5LO‐targeted gene brain over‐expression in these mice resulted in a worsening of behavioral and motor deficits. Over‐expression of 5LO resulted in microglia and astrocyte activation and significant synaptic pathology, which was associated with a significant elevation of tau phosphorylation at specific epitopes, tau insoluble fraction, and activation of the cdk5 kinase. In vitro studies confirmed that 5LO directly modulates tau phosphorylation at the same epitopes via the cdk5 kinase pathway. These data demonstrate that 5LO plays a direct role in tau phosphorylation and is an active player in the development of the entire tau phenotype. They provide further support to the hypothesis that 5LO is a viable therapeutic target for the treatment and/or prevention of human tauopathy.
Microdialysis as a tool to determine the local tissue concentration of dicloxacillin in man
Authors: Hansen Kristian Kraft , Nielsen Flemming , Stage Tore Bjerregaard , Jørgensen Uffe , Skov Ole , Rasmussen Lasse E. 
Published: November 2017

AimsThe most common pathogen to cause postoperative infections in Denmark is Staphylococcus aureus. Despite using prophylactic antibiotics, infections are still seen. Whether the tissue concentration is above the minimal inhibitory concentration (MIC) for the pathogen is unknown. Thus, the concentration of dicloxacillin in muscle and adipose tissue was measured after intravenous administration, in healthy men.MethodsMIC for dicloxacillin against S. aureus was determined using the broth macrodilution method. A microdialysis (MD) catheter was placed in the subcutaneous tissue of the abdomen and in the lateral vastus muscle of the thigh of six healthy male volunteers. They were given 2 g dicloxacillin intravenously. Samples from blood and MD fluid were collected. The unbound dicloxacillin was isolated from plasma. Samples were analysed with high performance liquid chromatography (HPLC).ResultsThe maximum concentration was reached in muscle tissue after 0.5 h and in adipose tissue after 0.8 h. AUC0–6h for the dicloxacillin concentration in adipose tissue was significantly lower when compared to the unbound dicloxacillin concentration in plasma. The dicloxacillin concentration was above the MIC for sensitive S. aureus for a minimum of 2.3 h and a median of 4.1 h in muscle tissue and a minimum of 1.8 h and a median of 3.2 h in adipose tissue.ConclusionsThe unbound dicloxacillin concentration in adipose and muscle tissue remained above the MIC for sensitive S. aureus, for a period sufficient for many orthopaedic procedures. Whether this is true in patients with compromised circulation remains to be investigated.
Population Pharmacokinetics of Fosdagrocorat (PF‐04171327), a Dissociated Glucocorticoid Receptor Agonist, in Patients With Rheumatoid Arthritis
Authors: Weatherley Barry , McFadyen Lynn , Tammara Brinda 
Published: November 2017

AbstractDissociated agonists of the glucocorticoid receptor (DAGRs) show similar antiinflammatory effects but improved tolerability compared with standard glucocorticoid receptor (GR) agonists. The prodrug fosdagrocorat (PF‐04171327), with active DAGR metabolite PF‐00251802 (Metabolite‐1), is postulated to show superior efficacy over placebo and prednisone in patients with moderate to severe rheumatoid arthritis (RA). We investigated the population pharmacokinetics of active Metabolite‐1 and its active metabolite PF‐04015475 (Metabolite‐2) in patients with moderate to severe RA enrolled in a 12‐week, phase II, randomized, double‐blind study (NCT01393639). A simultaneous fit of a two‐compartment model for Metabolite‐1 and a one‐compartment model for Metabolite‐2 provided an adequate fit to the data. Significant covariates included weight, with an additional female effect on clearance of Metabolite‐1 (∼26%) and Metabolite‐2 (∼33%) compared with males. Age influenced clearance of Metabolite‐1. In combination, age, weight, and sex predicted >twofold differences in area under the concentration–time curve of Metabolite‐1 at the extremes.
Localization of Gram Negative Urinary Tract Infection by Immunofluorescence in Infants and Children
Authors: BARNETT G. R. , ABBOTT G. D. 
Published: November 2017

Barnett, G. R. and Abbott, G. D. (1978). Aust. Paediatr. J., 14, 143–146. Localization of gram negative urinary tract infection by immunofluorescence in infants and children. Bladder urine samples from 97 gram negative urinary tract infections (U.T.Is) in infants and children were tested for antibody coated bacteria (A.C.B.) by immunofluorescence (I.F.). A.C.B. were detected in 14 of 44 episodes of acute pyelonephritis, one of 20 episodes of probable cystitis and five of 33 episodes of asymptomatic bacteriuria. Bladder washout localization reinforced the conclusion that negative I.F. tests are common in upper U.T.Is in infants and children.An association between A.C.B. and renal scarring was observed. Eight of 17 patients with A.C.B. had reflux nephropathy compared with four of 49 patients without A.C.B. Limitations of the test as a screening procedure for renal scarring were evident, however, after finding nine patients with A.C.B. and no renal scarring as well as four patients with renal scarring and no A.C.B.
Electroacupuncture in Rats Infected with Strongyloides venezuelensis: effects on gastrointestinal transit and parasitological measurements
Authors: dos Anjos-Ramos Luana , Gama Loyane Almeida , Hauschildt Andrieli Taise , Fujiwara Ricardo Toshio , Corá Luciana Aparecida , Américo Madileine Francely 
Published: November 2017

Objective To investigate the effects of electroacupuncture (EA) at ST36 and CV12 on gastrointestinal transit and parasitological measurements during Strongyloides venezuelensis infection in rats. Design Rats were infected with S. venezuelensis and allocated to one of three groups that were infected and remained untreated (SV group, n=8), infected and treated with EA at CV12 (SV+CV12 group, n=8) or infected and treated with EA at ST36 (SV+ST36 group, n=8). EA was performed every 3 days over a 21-day period, at 4 mA intensity and 15 Hz frequency for 20 min. At 2 and 20 days post-infection (dpi), body weight, food and water intake, and faecal characteristics were monitored over a 24-hour period. Gastric emptying, caecal arrival time, small intestinal transit and eggs per gram (EPG) of faeces were calculated at 3, 9, 15 and 21 dpi. At 21 dpi, intestinal worm recovery was counted. Results EA at ST36 and CV12 slowed gastric emptying over the course of infection time. An accelerated intestinal transit was observed in the ST36 group, and after CV12 treatment the same effect was observed at 9 and 15 dpi. At 9 dpi, EPG was increased in the CV12 group. ST36 treatment decreased EPG at 9 and 15 dpi. At 21 dpi, both the ST36 and CV12 groups had increased EPG and worm numbers. No changes were observed in the other parameters analysed. Conclusions EA at ST36 and CV12 provoked changes in gastrointestinal transit that may be beneficial to the host during S. venezuelensis infection; however, based on the number of worms and EPG at 21 dpi, the indication for EA in the treatment of strongyloidiasis needs to be carefully assessed.
Effects of Scalp Electroacupuncture on the Pi3K/Akt Signalling Pathway and Apoptosis of Hippocampal Neurons in a Rat Model of Cerebral Palsy
Authors: Zhang Hanhong , Gao Jing , Wang Mengmeng , Yu Xuefeng , Lv Xiuhua , Deng Huan , Fan Xiangwei , Chen Kaiyun 
Published: November 2017

Background Substantial evidence from clinical reports has established that most cerebral palsy (CP) patients benefit from a comprehensive rehabilitation exercise training programme. Such advances are enhanced when scalp electroacupuncture (EA), applied at a location corresponding to the projection of the motor area, is combined with rehabilitation exercise training. However, little information exists regarding the mechanistic basis for these effects. Objective To examine whether EA stimulation within the scalp projection location of the motor area can inhibit apoptosis of hippocampal neurons by regulating the PI3k/Akt signalling pathway in a rat model of CP. Methods Fifty male Sprague-Dawley rats underwent surgical modelling of CP. Five were used to confirm successful establishment of the model and the remaining 45 rats were randomly divided into one of three groups that remained untreated (CP group, n=15) or received EA treatment alone (CP+EA group, n=15) or EA in combination with a PI3K/Akt inhibitor (CP+EA+LY294002 group, n=15)). An otherwise healthy negative control group of rats undergoing sham surgery was also included (Control group, n=15). In the CP+EA and CP+EA+LY294002 groups, EA was applied to the scalp surface at alocation corresponding to the projection of the motor area. Basso, Beattie and Bresnahan (BBB) locomotor scores, hippocampal protein expression of Akt and p-Akt (by Western blot analysis) and neuronal apoptosis in hippocampal tissue (by histopathology) were assessed at 7, 14 and 21 days post-CP induction. Results CP rats receiving scalp EA treatment demonstrated improved behavioural scores, less hippocampal neuronal apoptosis and higher expression levels of Akt and p-Akt (p<0.05) at all time points studied compared with untreated CP rats. There were no significant differences observed between CP+EA+LY294002 and untreated CP model groups. Conclusions The effects of scalp EA on the PI3K/ Akt signalling pathway may represent one of the mechanisms involved in the inhibition of hippocampal neuronal apoptosis and improvement of deficits associated with CP in a rat model.
Tactile massage reduces rescue doses for pain and anxiety: an observational study
Authors: Pedersen Karina , Björkhem-Bergman Linda 
Published: November 2017

ObjectivesThe aim of this study was to evaluate the effect of tactile massage (TM) on palliative care patients.MethodAn observational study at a hospice ward in Sweden was carried out. Forty-one palliative patients were offered TM, at an average of three treatments per patient. Before and after every treatment, self-assessed pain, well-being and anxiety according to the Edmonton Symptom Assessment Scale (0–10) were recorded. In addition, the number of rescue doses for pain and anxiety was monitored 24 hours before and after the treatment and in two consecutive days before the patients were offered TM (control data).ResultsTM resulted in improvement of self-assessed pain by 1.7 points (SD 1.6), anxiety by 2.3 points (SD 2.0) and well-being by 2.6 points (SD 1.4). The number of rescue doses for pain was reduced from 1.6 to 0.84 doses/patient (P<0.001) and for anxiety from 0.52 to 0.24 doses/patient (P<0.01). The number of rescue doses was not changed in the same patients in two consecutive days before the patients were offered TM. The effect was evident already after the first treatment and did not increase further with repeated treatments. No patients reported any harmful effects of the treatment.ConclusionTM reduced the need for administration of rescue doses for pain and anxiety and improved well-being in palliative care patients. Larger randomised studies with parallel control groups are needed to confirm the findings from this observational pilot study.
A prospective study of faecal immunochemical testing following polypectomy in a colorectal cancer screening population
Authors: Gibson David J , Nolan Blathnaid , Rea Joanna , Buckley Maire , Horgan Gareth , Sheahan Kieran , Doherty Glen A , O’Donoghue Diarmuid , Mulcahy Hugh E , Smith Alan , Cullen Garret 
Published: November 2017

Introduction52% of faecal immunohistochemistry test (FIT)-positive clients in the Irish National Colorectal Cancer Screening Programme (BowelScreen) have adenomatous polyps identified at colonoscopy in round 1. Although it is known that advanced adenomas and cancers cause an elevated FIT, it is not known if small (<5 mm) adenomas cause a positive FIT.AimsDetermine if removal of small polyps in an FIT-based colorectal cancer (CRC) screening programme is associated with a negative FIT on follow-up.MethodsA single-centre prospective observational study of consecutive participants attending for first round screening colonoscopy who had a positive FIT (>45 µg Hb/g) as part of the Irish Colorectal Cancer Screening Programme. Subjects were consented at the time of colonoscopy and were sent a repeat FIT 4–6 weeks later. Precolonoscopy and postcolonoscopy FITs were compared and correlated with clinical findings and endoscopic intervention.Results112 consecutive first round participants were recruited. Eight (7%) had cancer, 75 (67%) adenomatous polyps, 17 (15%) a normal colonoscopy and 12 (11%) other pathology. There was a clear difference in median FIT levels between the four groups (P=0.006). Advanced pathology (tumour or adenomatous polyp >1 cm) was associated with higher FIT than non-advanced pathology (median FIT 346 vs 89 P=0.0003). 83% (86/104) of subjects completed a follow-up FIT. Follow-up FIT remained positive in 20% (17/86). Polypectomy was associated with a reduction in FIT from a median of 100 to 5 µg Hb/g (P<0.0001). Removal of polyps >5 mm was the only factor independently associated with a negative follow-up FIT on multivariate analysis (OR 3.9 (1.3–11.9, P=0.04)).ConclusionFIT is a sensitive test and levels increase with advanced colonic pathology. Polypectomy of advanced adenomas is associated with a negative follow-up FIT. However, alternative causes for a positive FIT should be considered in patients who have adenomas less than 5 mm detected or a normal colonoscopy.
Where do women and men in Britain obtain contraception? Findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)
Authors: French Rebecca S , Geary Rebecca , Jones Kyle , Glasier Anna , Mercer Catherine H , Datta Jessica , Macdowall Wendy , Palmer Melissa , Johnson Anne M , Wellings Kaye 
Published: November 2017

IntroductionTo estimate the prevalence of use of different sources of contraceptive supplies in Britain and its variation by key demographic and behavioural characteristics.MethodsCross-sectional probability sample survey of women and men aged 16–74 years, resident in Britain, interviewed between 2010 and 2012. Analyses reported here were of 4571 women and 3142 men aged 16–44 years who reported having vaginal sex in the past year. Those relying exclusively on sterilisation (including hysterectomy) were excluded. Sources of contraceptive supplies were categorised as: general practice, community clinic, retail and other. Prevalence of use of these sources was estimated, and associated factors examined.ResultsSome 87.0% of women and 73.8% of men accessed at least one source of contraceptive supplies in the previous year. Most women (59.1%) used general practice and most men (54.6%) used retail outlets. Community clinics were less commonly used, by 23.0% of women and 21.3% of men, but these users were younger and at greater sexual health risk. These associations were also observed among the 27.3% of women and 30.6% of men who used more than one source category (general practice, community clinic or retail) for contraceptive supplies.ConclusionsPeople in Britain use a variety of sources to obtain contraceptive supplies and some sources are more commonly used by those more vulnerable to poorer sexual health. Our findings suggest that national policy changes to increase access to contraceptive methods have had an effect on the diversity of services used.
Counselling to include tailored use of combined oral contraception in clinical practice: an evaluation
Authors: Akintomide Hannat , Rank Katherine Margaret , Brima Nataliya , McGregor Fiona , Stephenson Judith 
Published: November 2017

BackgroundCombined oral contraception (COC, ‘the pill’) remains the most prescribed method of contraception in the UK. Although a variety of regimens for taking monophasic COC are held to be clinically safe, women are not routinely counselled about these choices and there is a lack of evidence on how to provide this information to women.AimTo assess the usefulness and feasibility of including tailored use of monophasic COC within routine COC counselling in a sexual and reproductive health (SRH) service using a structured format.MethodUsing a structured format, healthcare professionals (HCPs) counselled new and established COC users attending an SRH service about standard and tailored ways of taking the pill. Questionnaires were used to survey both the HCPs and patients immediately after the initial consultation, and then the patients again 8 weeks later.ResultsNearly all patients (98%, n=95) felt it was helpful to be informed of the different ways of using monophasic COC by the HCP, without giving too much information at one time (96%, n=108). The HCPs were confident of their COC counselling (99%, n=110) and did not think the consultations took significantly longer (88%, n=98).ConclusionThis study demonstrates that information on different pill taking regimens is useful and acceptable to patients, and can improve contraceptive pill user choice. It is also feasible for HCPs to perform COC counselling to include tailored pill use during routine consultations in a clinical setting.
Clinical physiotherapists’ experiences of leadership in physiotherapy in Ireland
Authors: McGowan Emer , Walsh Cathal , Stokes Emma 
Published: November 2017

BackgroundPrevious studies indicated that physiotherapy managers and clinical specialists perceive themselves to be most effective at demonstrating leadership capabilities associated with the human resource and structural frames.AimTo investigate physiotherapists’ perceptions of the leadership capabilities of physiotherapy management in their workplace.MethodsA quantitative study was performed using a paper-based survey with a purposive sample of physiotherapists. The survey asked participants to rate 24 leadership capabilities on two questions: ‘How important are these capabilities for physiotherapy management to demonstrate?’ and ‘How effective is physiotherapy management in your workplace at demonstrating these capabilities?’ The leadership capabilities were derived from the leadership framework of Bolman and Deal.ResultsThe response rate was 55% (n=303). The Friedman test indicated that there was a significant difference in the ratings of importance of the leadership capabilities across the frames (X2(3)=9.362, P=0.025). Post-hoc analysis demonstrated that the symbolic leadership capabilities were rated more highly for importance than the structural leadership capabilities (Z=−2.640, P=0.008). There was also a significant difference in the ratings of effectiveness on the leadership capabilities across the frames (X2(3)=78.022, P<0.001). Physiotherapy management were rated as most effective at demonstrating structural and political frame capabilities and least effective on symbolic frame capabilities.ConclusionsThere is a discrepancy between the leadership capabilities that physiotherapists perceive physiotherapy management to be most effective at demonstrating and the leadership capabilities they perceive to be most important. Physiotherapy management may benefit from specific leadership programmes to develop their leadership capabilities in the symbolic frame.
Design for simultaneous acceleration of stable and unstable beams in a superconducting heavy-ion linear accelerator for RISP
Authors: Kim Jongwon , Son Hyock-Jun , Park Young-Ho 
Published: November 2017

The post-accelerator of isotope separation on-line (ISOL) system for rare isotope science project (RISP) is a superconducting linear accelerator (SC-linac) with a DC equivalent voltage of around 160 MV. An isotope beam extracted from the ISOL is in a charge state of [Formula: see text] and its charge state is increased to [Formula: see text] by charge breeding with an electron beam ion source (EBIS). The charge breeding takes tens of ms and the pulse width of extracted beam from the EBIS is tens of [Formula: see text]s, which operates at up to 30 Hz. Consequently a large portion of radio frequency (rf) time of the post SC-linac is unused. The post-linac is equipped also with an electron cyclotron resonance (ECR) ion source for stable ion acceleration. Thanks to the large phase acceptance of SC-linac, it is possible to accelerate simultaneously both stable and radioisotope ions with a similar charge to mass ratio by sharing rf time. This operation scheme is implemented for RISP with the addition of an electric chopper and magnetic kickers. The facility will be capable of providing the users of the ISOL and in-flight fragmentation (IF) systems with different beams simultaneously, which would help nuclear science users in obtaining a beam time as high-precision measurements often need long hours.
Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo‐Controlled Study
Authors: Gunawardhana Lhanoo , McLean Lachy , Punzi Henry A. , Hunt Barbara , Palmer Robert N. , Whelton Andrew , Feig Daniel I. 
Published: November 2017

Background

Hyperuricemia is associated with hypertension, with elevated serum uric acid levels postulated to have a causal role in the development of hypertension. Consequently, serum uric acid reduction may help lower blood pressure (
BP
). A Phase 2, double‐blind, placebo‐controlled trial was conducted to assess the potential
BP
‐lowering effects of the xanthine oxidase inhibitor febuxostat in subjects with hypertension and hyperuricemia (serum uric acid ≥0.42 mmol/L [≥7.0 mg/dL]).

Methods and Results

Subjects (n=121) were randomized 1:1 to febuxostat 80 mg once daily or to placebo. The primary end point was change from baseline to Week 6 in 24‐hour mean ambulatory systolic
BP
(
SBP
). Additional end points included the following: change from baseline to Week 3 in 24‐hour mean
SBP
and changes from baseline to Weeks 3 and 6 in 24‐hour mean ambulatory diastolic
BP
, serum uric acid, mean daytime and nighttime ambulatory
SBP
/diastolic
BP
, and clinic
SBP
/diastolic
BP
. For the overall study population, there were no significant differences between febuxostat and placebo for changes from baseline to Weeks 3 or 6 in ambulatory, daytime or nighttime, or clinic
SBP
or diastolic
BP
. However, in a preplanned subgroup analysis, there was a significant decrease in
SBP
from baseline to Week 6 in subjects with normal renal function (estimated glomerular filtration rate ≥90 mL/min) treated with febuxostat versus placebo; least squares mean difference, −6.7; 95% confidence interval −13.3 to −0.0;
P
=0.049.

Conclusions

This study suggests that febuxostat may lower
BP
in hyperuricemic patients with hypertension and normal renal function; further studies should be conducted to confirm this finding.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01496469.