bluuebunny/crossref_metadata_2025_split huggingface dataset:
Valproic acid protects against haemorrhagic shock‐induced signalling changes via PPARγ activation in an in vitro model
Authors: Zuckermann Alexandra M E , La Ragione Roberto M , Baines Deborah L , Williams Robin S B 
Published: September 2015

Background and PurposeValproic acid (VPA), a widely used epilepsy and bipolar disorder treatment, provides acute protection against haemorrhagic shock‐induced mortality in a range of in vivo models through an unknown mechanism. In the liver, this effect occurs with a concomitant protection against a decrease in GSK3β‐Ser9 phosphorylation. Here, we developed an in vitro model to investigate this protective effect of VPA and define a molecular mechanism.Experimental ApproachThe human hepatocarcinoma cell line (Huh7) was exposed to conditions occurring during haemorrhagic shock (hypoxia, hypercapnia and hypothermia) to investigate the changes in GSK3β‐Ser9 phosphorylation for a 4 h period following treatment with VPA, related congeners, PPAR agonists, antagonists and siRNA.Key ResultsHuh7 cells undergoing combined hypoxia, hypercapnia, and hypothermia reproduced the reduced GSK3β‐Ser9 phosphorylation shown in vivo during haemorrhagic shock, and this change was blocked by VPA. The protective effect occurred through upstream PTEN and Akt signalling, and prevented downstream β‐catenin degradation while increasing histone 2/3 acetylation. This effect was reproduced by several VPA‐related compounds with known PPARγ agonist activity, independent of histone deacetylase (HDAC) inhibitory activity. Specific pharmacological inhibition (by T0070907) or knockdown of PPARγ blocked the protective effect of VPA against these signalling changes and apoptosis. In addition, specific activation of PPARγ using ciglitazone reproduced the changes induced by VPA in haemorrhagic shock‐like conditions.Conclusion and ImplicationsChanges in GSK3β‐Ser9 phosphorylation in in vivo haemorrhagic shock models can be modelled in vitro, and this has identified a role for PPARγ activation in the protective role of VPA.
The employment dynamics of less‐educated men in the United States: The role of self‐employment
Authors: Ahn Taehyun 
Published: September 2015

AbstractUsing data from the 1979 National Longitudinal Survey of Youth, I construct a sample of working‐age males and examine the employment dynamics with a particular focus on the role of self‐employment for less‐educated men in the US. I find that men responding they had at some point been self‐employed tend to spend less time in non‐employment than other less‐educated men. The results from the dynamic multinomial logit model reveal positive aspects of self‐employment by indicating that less‐educated men who were self‐employed in the previous year were less likely to be non‐employed in the future as compared to those who were paid workers in the previous year.
What young people with spina bifida want to know about sex and are not being told
Authors: Akre C. , Light A. , Sherman L. , Polvinen J. , Rich M. 
Published: September 2015

AbstractObjectiveThe aim of this paper was to examine sexual knowledge, concerns and needs of youth with spina bifida (SB) to inform the medical community on ways to better support their sexual health.MethodsAs part of the Video Intervention/Prevention Assessment (VIA) – transitions, a prospective cohort study, 309 h of video data were collected from 14 participants (13–28 years old) with SB. Participants were loaned a video camcorder for 8–12 weeks to shoot visual narratives about any aspects of their lives. V/A visual narratives were analysed with grounded theory using NVivo.ResultsOut of 14 participants, 11 (six women) addressed issues surrounding romantic relationships and sexuality in their video clips. Analysis revealed shared concerns, questions and challenges regarding sexuality gathered under four main themes: romantic relationships, sexuality, fertility and parenthood, and need for more talk on sexuality.ConclusionsYouth with SB reported difficulties in finding answers to questions regarding their sexuality, romantic relationships and fertility. This study revealed a need for help from the medical community to inform and empower youth with SB in the area of sexual health. Through sexual and reproductive health education with patients and parents starting at an early age, medical providers can further encourage healthy emotional and physical development in adolescents transitioning into adulthood.
Prenatal exposure to persistent organic pollutants and offspring allergic sensitization and lung function at 20 years of age
Authors: Hansen S. , Strøm M. , Olsen S. F. , Dahl R. , Hoffmann H. J. , Granström C. , Rytter D. , Bech B. H. , Linneberg A. , Maslova E. , Kiviranta H. , Rantakokko P. , Halldorsson T. I. 
Published: September 2015

SummaryBackgroundPrenatal exposures to persistent organic pollutants (POPs) have been associated with asthma medication use and self‐reported symptoms, but associations with lung function and allergic sensitization have been minimally explored. The aim of the study was to examine the associations between prenatal exposures to POPs and allergic sensitization and lung function in 20‐year‐old offspring.MethodsIn a Danish cohort of 965 pregnant women established in 1988–1989, six polychlorinated biphenyl (PCB) congeners, hexachlorobenzene (HCB), and dichlorodiphenyldichloroethylene (p,p’‐DDE) were quantified in archived maternal serum drawn in gestational week 30 (n = 872). Among those with available maternal exposure information, at age 20, 421 offspring attended attended a clinical examination including measurements of allergic sensitization (serum‐specific IgE ≥ 0.35 kUA/L) (n = 418) and lung function [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] (n = 414).ResultsThere were no associations between maternal concentrations of POPs and offspring allergic sensitization at 20 years of age. Maternal concentrations of POPs were, however, positively associated with offspring airway obstruction (FEV1/FVC < 75%). Compared to offspring in the first tertile of exposure, offspring in the third tertile of dioxin‐like PCB exposure had an OR of 2.96 (95% CI: 1.14–7.70). Similar associations for non‐dioxin‐like PCBs, HCB, and p,p’‐DDE were 2.68 (1.06–6.81), 2.63 (1.07, 6.46), and 2.87 (1.09, 7.57), respectively. No associations were observed with reduced lung function (FEV1% of predicted value < 90%).Conclusion and Clinical RelevanceOur data indicate that prenatal exposure to POPs appears to be associated with airway obstruction but not allergic sensitization at 20 years of age. The findings support that chronic obstructive lung diseases may have at least part of their origins in early life.
Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults
Authors:   VRC 602 Study Team, Ledgerwood J E , Coates E E , Yamshchikov G , Saunders J G , Holman L , Enama M E , DeZure A , Lynch R M , Gordon I , Plummer S , Hendel C S , Pegu A , Conan-Cibotti M , Sitar S , Bailer R T , Narpala S , McDermott A , Louder M , O'Dell S , Mohan S , Pandey J P , Schwartz R M , Hu Z , Koup R A , Capparelli E , Mascola J R , Graham B S 
Published: September 2015

Summary
VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 μg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 μg/ml for the same two doses. Over the 5–40 mg/kg i.v. dose range (n = 18), the clearance was 0·016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.
Patients with Pendred syndrome: is cochlear implantation beneficial?
Authors: van Nierop J.W.I. , Huinck W.J. , Pennings R.J.E. , Admiraal R.J.C. , Mylanus E.A.M. , Kunst H.P.M. 
Published: September 2015

ObjectiveTo evaluate the benefit of cochlear implantation in patients with Pendred syndrome.DesignRetrospective study.SettingTertiary centre.Participants and main outcome measuresSpeech perception was measured using a phonetically balanced word list at a sound pressure level of 65 dB. Post‐operative phoneme scores at 12‐month for adults and 36‐month for children with Pendred syndrome were compared to scores of patients with an enlarged vestibular aqueduct (EVA) and a reference group with an unknown cause of hearing impairment. Quality of life was measured with the Nijmegen Cochlear Implant Questionnaire to evaluate the differences between pre‐ and post‐implantation.ResultsThe mean post‐operative phoneme scores were as follows: in the Pendred group, 91% (n = 16; SD = 10) for children and 78% (n = 7; SD = 14) for adults; in the reference group, 79% (n = 59; SD = 20) for children and 73% (n = 193; SD = 18) for adults; and in the EVA group, 84% (n = 6; SD = 7) for children and 66% (n = 12; SD = 22) for adults. A significant difference in speech perception was found between the children of the Pendred group and the reference group of 11.4% (SE = 5.2; P = 0.031). Between the adults, a difference of 11.2% (SE = 6.7; P = 0.094) was found. The difference between the Pendred group and the EVA group was 5.7%(SE = 4.5; P = 0.22) for children and 9.9% (SE = 8.7; P = 0.28) for adults. A significant improvement post‐implantation in four of the six subdomains of the quality of life questionnaire was found: basic sound perception (P = 0.002), advanced sound perception (P = 0.004), speech production (P = 0.018) and activity limitations (P = 0.018). The two not significant subdomains were self‐esteem (P = 0.164) and social interaction (P = 0.107).ConclusionsAfter cochlear implantation, children with Pendred syndrome performed better than the reference group with respect to speech perception, however, adults performed similar. No significant differences were found between the Pendred and EVA group. Consequently, during pre‐operative counselling, the two groups of patients may be considered comparable in terms of expected speech perception performance after cochlear implantation.
High frequency of contact allergy to implant and bone cement components, in particular gentamicin, in cemented arthroplasty with complications: usefulness of late patch test reading
Authors: Thomas Benjamin , Kulichova Daniela , Wolf Ronald , Summer Burkhard , Mahler Vera , Thomas Peter 
Published: September 2015

SummaryBackgroundArthroplasty patients with complications may be sensitized to implant components.ObjectivesTo quantify patch test reactions to implant materials in aseptic cemented arthroplasty patients with complications, and to evaluate the benefit of late patch test reading at D6.MethodsAnalyses of patch test reactions to baseline series and bone cement components and of the questionnaire‐aided histories of 250 consecutive patients with suspected implant allergy were performed. Patch tests were read at D2, D3, and D6.ResultsThere were 187 positive reactions to the 29 allergens of the baseline series, and 52 to the seven allergens of the bone cement series. Forty‐nine of 250 patients reacted to the bone cement series. In contrast to ‘early allergens’ such as fragrance mix, late reading at D6 increased the number of positive reactions by 11/32 for nickel, 1/5 for cobalt, and 2/4 for chromium. With bone cement components, most reactions were to gentamicin (25 of 250 patients), and 17 of 25 appeared only at D6.ConclusionLate reading is useful for patch tests with metals and bone cement components. With only D2/D3 readings, 32 reactions to nickel, cobalt, chromium and bone cement components would have been missed. This underlines the utility of late reading in general and in complicated cemented arthroplasty patients, given the unexpectedly high number of gentamicin reactions.
The bowel cancer awareness campaign ‘Be Clear on Cancer’: sustained increased pressure on resources and over‐accessed by higher social grades with no increase in cancer detected
Authors: Hall S. J. , Peacock J. D. H. , Cochrane L. A. , Peacock O. , Tierney G. M. , Tou S. I. H. , Lund J. N. 
Published: September 2015

AbstractAimTo evaluate the impact of the national ‘Be Clear on Cancer’ bowel cancer reminder campaign on service and diagnosis at a single UK institution. Secondly, to evaluate the socio‐economic background of patients referred before and after the reminder campaign compared with the regional demographic.MethodSuspected cancer 2‐week wait patients in the 3 months precampaign, postcampaign and after the reminder campaign were included. Demographics, investigations and diagnosis were recorded. The postcode was used to allocate a National Readership Survey social grade.ResultsThree hundred and eighty‐three referrals were received in the 3 months precampaign, 550 postcampaign and 470 postreminder campaign. There were significant increases in the monthly referral rates following the campaign (P < 0.001 in both the post‐ and postreminder periods). Significantly more patients from social grades AB and C1C2 than expected from regional demographics were referred precampaign and after the reminder campaign (P < 0.001 in each case). There were no significant differences between the proportions of patients diagnosed with colorectal cancer in the three study periods (P = 0.710).ConclusionThe ‘Be Clear on Cancer’ bowel cancer campaign has had a significant sustained impact on resources. It has failed to increase referrals among lower socio‐economic grades, leading to an increase in ‘worried well’ referrals and no change in numbers, or the stage, of colorectal cancers diagnosed.
Faculty Participation in and Needs around Community Engagement within a Large Multiinstitutional Clinical and Translational Science Awardee
Authors: Chung Bowen , Norris Keith , Mangione Carol , del Pino Homero E. , Jones Loretta , Castro Daniel , Wang Christina , Bell Douglas , Vangala Sitaram , Kahn Katherine , Brown Arleen F. 
Published: September 2015

AbstractCommunity engagement is recommended to ensure the public health impact of NIH‐funded science. To understand the prevalence of community‐engaged research and faculty interest in and needs around this, from 2012 to 2013, an online survey (n = 3,022) was sent to UCLA Clinical and Translational Science Institute faculty. Among respondents, 45% reported community‐engaged project participation in the last year and 64% an interest in learning about community‐engaged research. Over 50% indicated career development and pilot grants would increase participation in community‐engaged research. A greater percentage of pretenure than tenured faculty (pretenure 54.9%, tenured 42.2%, p = 0008) noted faculty promotion criteria incentivizing community‐engaged research would increase participation. In adjusted analyses, African American (OR 4.06, CI 1.68–9.82, p = 0.002) and Latino (OR 1.91, CI 1.10–3.33, p = 0.022) faculty had higher odds of prior participation in community‐engaged projects than Whites. Female faculty had greater odds of interest (OR 1.40, CI 1.02–1.93, p = 0.038) in learning about community‐engaged research than males. African American (OR 4.31, CI 1.42–13.08, p = 0.010) and Asian/Pacific Islander (OR 2.24, CI 1.52–3.28, p < 0.001) faculty had greater interest in learning about community‐engaged research than Whites. To build community‐engaged faculty research capacity, CTSAs’ may need to focus resources on female and minority faculty development.
Applying Process Improvement Methods to Clinical and Translational Research: Conceptual Framework and Case Examples
Authors: Daudelin Denise H. , Selker Harry P. , Leslie Laurel K. 
Published: September 2015

AbstractThere is growing appreciation that process improvement holds promise for improving quality and efficiency across the translational research continuum but frameworks for such programs are not often described. The purpose of this paper is to present a framework and case examples of a Research Process Improvement Program implemented at Tufts CTSI. To promote research process improvement, we developed online training seminars, workshops, and in‐person consultation models to describe core process improvement principles and methods, demonstrate the use of improvement tools, and illustrate the application of these methods in case examples. We implemented these methods, as well as relational coordination theory, with junior researchers, pilot funding awardees, our CTRC, and CTSI resource and service providers. The program focuses on capacity building to address common process problems and quality gaps that threaten the efficient, timely and successful completion of clinical and translational studies.
The extramedical use and diversion of opioid substitution medications and other medications in prison settings in Australia following the introduction of buprenorphine–naloxone film
Authors: White Nancy , Ali Robert , Larance Briony , Zador Deborah , Mattick Richard P. , Degenhardt Louisa 
Published: September 2015

AbstractIntroduction and AimsAround 65% of people incarcerated in prisons in Australia, America and Europe have a history of drug dependence, sometimes treated with opioid substitution treatment (OST) medications. Studies report that those in treatment in prison do engage in some level of diversion to others, whether on a voluntary or coerced basis. We aimed to examine the use of prescribed and non‐prescribed OST medications by those in prisons, especially buprenorphine–naloxone film (BNX‐F); the extent of non‐adherence and diversion and reasons for such practices; and the impact of the introduction of BNX‐F into the prison system.Design and MethodsMixed methods study drawing on: (i) structured interviews with current OST clients (n = 60) who reported being incarcerated in the 12 months prior to being interviewed and (ii) qualitative interviews with key experts working in corrections and prison (or justice) health settings.ResultsThe majority were prescribed OST medications in prison, with 25% removing all or part of their supervised dose on at least one occasion, and 44% reporting use of non‐prescribed medications. Some reported intravenous use (14% injected). One‐third of OST recipients reported selling/sharing OST medications with others in prison. The introduction of BNX‐F into the prison system saw different diversion methods used and removal from dosing within prison.Discussion and ConclusionsDespite prison being a highly regulated and controlled environment, some level of diversion and sharing of psychoactive medication occurs among prisoners. The buprenorphine formulations used in OST present particular challenges with respect to supervised dosing in this setting. [White N, Ali R, Larance B, Zador D, Mattick RP, Degenhardt L. The extramedical use and diversion of opioid substitution medications and other medications in prison settings in Australia following the introduction of buprenorphine–naloxone film. Drug Alcohol Rev 2015;●●:●●–●●]
Effect of 4 years subcutaneous insulin infusion treatment on albuminuria, kidney function and HbA1c compared with multiple daily injections: a longitudinal follow‐up study
Authors: Rosenlund S. , Hansen T. W. , Andersen S. , Rossing P. 
Published: September 2015

AbstractAimThe effect of insulin pump [continuous subcutaneous insulin infusion (CSII)] treatment on diabetes complications in a modern clinical setting is largely unknown. We investigated the effect of 4 years CSII treatment on HbA1c, albuminuria and kidney function compared with multiple daily injections (MDI) in a single‐centre clinical setting.MethodsAll patients initiating CSII treatment from 2004 to 2010 and followed for at least 4 years were included in the study: 193 people with Type 1 diabetes were matched (1 : 2) with 386 patients treated with MDI in the same period. Matching was based on diabetes duration, gender, HbA1c and normo‐, micro‐ or macroalbuminuria at baseline. Urinary albumin/creatinine ratio (UACR) was measured yearly and annual change assessed from linear regression.ResultsCSII‐ vs. MDI‐treated patients were comparable at baseline. After 4 years, HbA1c was 62 ± 11 vs. 68 ± 11 mmol/mol (7.8 ± 1.0 vs. 8.4 ± 1.0%) (P < 0.001). Annual UACR change in CSII‐ vs. MDI‐treated patients was [mean (95% confidence interval)] −10.1 (−13.3; −6.8) vs. −1.2 (−3.6; 0.9)% (P < 0.001). Reduction in UACR was significantly associated with CSII treatment after adjustment for age, gender, diabetes duration, estimated GFR, UACR, mean arterial pressure, HbA1c, cholesterol, renin–angiotensin–aldosterone system inhibition, anti‐hypertensive treatment and smoking (P < 0.001). This remained significant (P < 0.001) when only including patients on stable renin–angiotensin–aldosterone system inhibition during follow‐up (n = 465).ConclusionsTreatment with CSII over 4 years independently reduced HbA1c and UACR compared with MDI. Reduced UACR may be due to less glycaemic variability because the effect of CSII on HbA1c could only partially explain the effect. This needs confirmation in randomized controlled trials.
The topographic specificity of muscle reinnervation predicts function
Authors: O'Daly Andres , Rohde Charles , Brushart Thomas 
Published: September 2015

AbstractFunctional testing has assumed a progressively dominant role in validating the success of experimental nerve repair. Results obtained in one model, however, cannot predict the results in others because they reflect the coordinated interaction of several muscles across multiple joints. As a result, many combinations of topographically correct and incorrect muscle reinnervation could produce the same result. We have developed a binary model in which elbow flexors and extensors are reinnervated, and elbow flexion and extension are the functions tested. The musculocutaneous and radial nerves of Lister‐Hooded rats were subjected to axonotmetic injuries that produced increasing degrees of axonal misdirection at the site of injury ranging from simple crush to transection and rotational offset of proximal and distal stumps. Elbow function was tested with a device that requires coordinated elbow extension to reach sugar pellets and flexion to return them to the mouth. After 12 weeks of regeneration, motoneurons projecting to the distal musculocutaneous nerve were retrogradely labelled with WGA‐Ruby and scored regarding their location within musculocutaneous or radial motoneuron pools. The severity of axonal misdirection resulting from the initial surgery was mirrored by progressive degrees of inappropriate reinnervation of the musculocutaneous nerve by radial nerve axons. The specificity of reinnervation predicted elbow function (r = 0.72), whereas the number of motoneurons regenerating did not. This model is thus well suited to study the interaction of regeneration specificity and function across a single joint, and to produce data that can be generalized more broadly than those obtained from more complex models.