bluuebunny/crossref_metadata_2025_split huggingface dataset:
White matter alterations in cocaine users are negatively related to the number of additionally (ab)used substances
Authors: Kaag Anne Marije , van Wingen Guido A. , Caan Matthan W. A. , Homberg Judith R. , van den Brink Wim , Reneman Liesbeth 
Published: February 2016

AbstractDiffusion tensor imaging studies have provided evidence for white matter (WM) alterations in cocaine users. While polysubstance use is a widespread phenomenon among cocaine users, its role in WM alterations in cocaine users is currently unknown. This study examined the relation between the number of substances that are used(cocaine, alcohol and marijuana) and WM alterations in 67 male non‐drug users and 67 male regular cocaine users, who were classified into five groups based on the number of used substances. Diffusion‐weighted images were acquired on a 3.0 T magnetic resonance imaging scanner. Using tract‐based spatial statistics we demonstrated that there was a negative relation between the number of used substances and fractional anisotropy, a global measure of WM integrity. Also, we demonstrated a positive relation between the number of used substance and radial diffusivity within the prefrontal lobe, suggesting an increase in demyelination with the number of used substances. We did not find a dose‐effect between the level of substance use and WM alterations. The results of the current study may reflect the presence of a pre‐existing vulnerability to polysubstance use resulting from prefrontal WM abnormalities and related impaired cognitive control although WM alterations because of polysubstance use cannot be fully excluded. This study is an important first step in understanding the problems related to polysubstance use among cocaine users.
Effect of monoclonal antibodies to PCSK9 on high‐sensitivity C‐reactive protein levels: a meta‐analysis of 16 randomized controlled treatment arms
Authors: Sahebkar Amirhossein , Di Giosia Paolo , Stamerra Cosimo Andrea , Grassi Davide , Pedone Claudio , Ferretti Gianna , Bacchetti Tiziana , Ferri Claudio , Giorgini Paolo 
Published: February 2016

AimsProprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging class of low‐density lipoprotein cholesterol (LDL‐C)‐lowering agents. In spite of their known effects on lipids, the impact of these drugs on systemic inflammation is less known. We aimed to investigate the effect of PCSK9 inhibitors on high‐sensitivity C‐reactive protein (hs‐CRP) levels through a meta‐analysis of randomized controlled trials (RCTs).MethodsA systematic literature search of Medline, SCOPUS and Google Scholar was conducted up to December 2015 to identify RCTs assessing changes in hs‐CRP concentrations during treatment with PCSK9 inhibitors. Quantitative data synthesis was performed using a random‐effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics.ResultsSixteen treatment arms, with a total of 2546 participants, were included. Random‐effects meta‐analysis did not show any significant effect of PCSK9 inhibitors on hs‐CRP levels (WMD: 0.002 mg l–1, CI: –0.017, 0.021; P = 0.807; I2 = 37.26%). This effect size was robust, not sensitive to any single study, and not affected by the type of PCSK9 inhibitor (evolocumab: WMD: 0.002 mg l–1, CI: –0.02, 0.02; P = 0.855; alirocumab WMD: 0.15 mg l–1, CI: –0.11, 0.40; P = 0.259; I2 = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l–1, CI: –0.20, 0.46; P = 0.433; I2 = 55.19%; monthly: WMD: 0.003 mg l–1, CI: –0.01, 0.01; P = 0.59; I2 = 0%). Random‐effects meta‐regression did not suggest any association of changes in hs‐CRP levels with changes in plasma LDL‐C concentrations (P = 0.697) or cumulative dosage of the drug (P = 0.980).ConclusionsThis meta‐analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs‐CRP concentrations.
Interagency collaboration in children and young people's mental health: a systematic review of outcomes, facilitating factors and inhibiting factors
Authors: Cooper M. , Evans Y. , Pybis J. 
Published: February 2016

AbstractBackgroundIn the UK and internationally, there have been increasing calls for interagency collaboration across mental health services for children and young people. However, it is not clear whether such practices do, indeed, have a positive impact and, if so, what factors facilitate and inhibit collaboration across agencies.MethodsElectronic searches were carried out on seven key computerized bibliographic databases. For inclusion in the review, studies needed to report on close working by two or more services that provided mental health support for children and/or young people and that had some systematic collection of qualitative and/or quantitative data. Outcomes were analysed narratively, and facilitating and inhibiting factors were examined using thematic analysis.ResultsA final sample of 33 studies was identified from 4136 initial records. Outcomes were mixed, with some findings indicating that interagency collaboration was associated with greater service use and equity of service provision, but other suggesting negative outcomes on service use and quality. However, interagency collaboration was perceived as helpful and important by both service users and professionals, and collaborative initiatives were evaluated positively. The factors most commonly identified as facilitating interagency collaboration were good interagency communication, joint trainings, good understandings across agencies, mutual valuing across agencies, senior management support, protocols on interagency collaboration and a named link person. The most commonly perceived barriers to interagency collaboration were inadequate resourcing, poor interagency communication, lack of valuing across agencies, differing perspectives, poor understandings across agencies and confidentiality issues.ConclusionsThe results are consistent with findings from previous reviews of interagency collaboration across adult and child services: there were some indications of benefit; and facilitating and inhibiting factors involved working relationships and multi‐agency processes, resources and management. The identification of these factors has implications for practitioners, service managers, trainers, commissioners and researchers.
Differences in hospital attendance for anaphylaxis between immigrants and non‐immigrants: a cohort study
Authors: Norredam M. , Sheikh A. , Dynnes Svendsen K. , Holm Petersen J. , Garvey L. H. , Kristiansen M. 
Published: February 2016

SummaryBackgroundThe impact of migration on the risk of anaphylaxis remains unknown. We hypothesized that non‐Western immigrants have a lower incidence of anaphylaxis compared to Danish‐born. We investigated variations in hospital attendance for anaphylaxis between immigrants and Danish‐born including time‐ and age‐ trends.MethodsA register‐based, historical prospective cohort design. Refugees or family reunified immigrants (n = 127 250) who, between January 1, 1994 and December 31, 2010, obtained residency permits in Denmark were included and matched in a 1 : 6 ratio on age and sex with Danish‐born individuals (n = 740 600). Personal identification numbers were cross‐linked to the Danish National Patient Registry identifying all first‐time hospital attendances for anaphylaxis from January 1, 1994 and December 31, 2010. Incidence rate ratios were estimated, stratified for sex and region of birth, adjusting for age using a Cox regression model including the influence of duration of residence and age when residence was obtained.ResultsIn total 1053 hospital attendances for anaphylaxis were identified: 89 among non‐Western immigrants, 9 among Western immigrants and 955 among Danish‐born patients. Both male (RR = 0.65; 95%CI: 0.46;0.90) and female (RR = 0.64; 95%CI: 0.48;0.85) non‐Western immigrants had a significantly lower risk ratio of hospital attendance for anaphylaxis compared to Danish‐born. Compared to Danish‐born, non‐Western immigrants living in Denmark during the entire follow‐up period also showed a decreased risk (RR = 0.65; 95%CI: 0.34;1.25). Compared to Danish‐born, non‐Western immigrants who obtained residence permission as children had a decreased risk of hospital attendance for anaphylaxis (RR = 0.48; 95%CI: 0.25;0.91).ConclusionThis Danish register‐based study using nationwide data revealed fewer hospital attendances for anaphylaxis among non‐Western immigrants compared to Danish‐born; however this protection was lost over time.
Human islets and dendritic cells generate post-translationally modified islet autoantigens
Authors: McLaughlin R J , de Haan A , Zaldumbide A , de Koning E J , de Ru A H , van Veelen P A , van Lummel M , Roep B O 
Published: February 2016

SummaryThe initiation of type 1 diabetes (T1D) requires a break in peripheral tolerance. New insights into neoepitope formation indicate that post-translational modification of islet autoantigens, for example via deamidation, may be an important component of disease initiation or exacerbation. Indeed, deamidation of islet autoantigens increases their binding affinity to the T1D highest-risk human leucocyte antigen (HLA) haplotypes HLA-DR3/DQ2 and -DR4/DQ8, increasing the chance that T cells reactive to deamidated autoantigens can be activated upon T cell receptor ligation. Here we investigated human pancreatic islets and inflammatory and tolerogenic human dendritic cells (DC and tolDC) as potential sources of deamidated islet autoantigens and examined whether deamidation is altered in an inflammatory environment. Islets, DC and tolDC contained tissue transglutaminase, the key enzyme responsible for peptide deamidation, and enzyme activity increased following an inflammatory insult. Islets treated with inflammatory cytokines were found to contain deamidated insulin C-peptide. DC, heterozygous for the T1D highest-risk DQ2/8, pulsed with native islet autoantigens could present naturally processed deamidated neoepitopes. HLA-DQ2 or -DQ8 homozygous DC did not present deamidated islet peptides. This study identifies both human islets and DC as sources of deamidated islet autoantigens and implicates inflammatory activation of tissue transglutaminase as a potential mechanism for islet and DC deamidation.
Detecting Change over Time: A Comparison of the SLUMS Examination and the MMSE in Older Adults at Risk for Cognitive Decline
Authors: Howland Molly , Tatsuoka Curtis , Smyth Kathleen A. , Sajatovic Martha 
Published: February 2016

SummaryAimsTo directly compare the 1‐year stability of Mini‐Mental State Examination (MMSE) score and Saint Louis University Mental Status (SLUMS) examination score and correlate score changes with demographic variables, clinical factors, and functional domains.MethodsA sample of 304 study participants was recruited from residential and clinical settings in Ohio. Follow‐up assessments were administered after 1 year with a retention rate of 92% (n = 281). Functional domains included the Instrumental Activities of Daily Living (IADL) scale.ResultsMMSE and SLUMS scores correlated with each other (r = 0.65, P < 0.001) and with two functional measures, including the IADL (r = 0.27, r = 0.24, P < 0.001). However, the MMSE and SLUMS frequently placed the same subject into different categories. Rates of reversion and conversion varied between the two tests. The 1‐year changes in MMSE raw score correlated with changes in three functional domains as well as age (P < 0.05), while SLUMS raw score changes did not correlate with any functional measures.ConclusionOur large, longitudinal data set allowed us to compare the tests' stability, which differed between the SLUMS and MMSE. The MMSE may be more sensitive than the SLUMS to 1‐year cognitive changes influencing functional abilities.
DopAmide: Novel, Water‐Soluble, Slow‐Release l‐dihydroxyphenylalanine (l‐DOPA) Precursor Moderates l‐DOPA Conversion to Dopamine and Generates a Sustained Level of Dopamine at Dopaminergic Neurons
Authors: Atlas Daphne 
Published: February 2016

SummaryBackgroundLong‐term l‐dihydroxyphenylalanine (l‐DOPA) treatment of Parkinson's disease (PD) is associated with motor complications known as l‐DOPA‐induced dyskinesias (LID) and on/off fluctuations, which are linked to unsteady pulsatile dopaminergic stimulation.AimThe objective of this study was to improve l‐DOPA treatment by slowing and stabilizing dopamine (DA) production in the brain and increasing water solubility to provide a rescue therapy for PD.ResultsWe synthesized l‐DOPA‐amide, a novel l‐DOPA precursor called DopAmide. DopAmide is water soluble and, as a prodrug, requires hydrolysis prior to decarboxylation by the aromatic l‐amino acid decarboxylase (EC 4.1.1.28; AAAD). In the 6‐OH‐dopamine (6‐OHDA)‐lesioned rats, DopAmide maintained steady rotations for up to 4 h compared with 2 h by l‐DOPA, suggesting that this rate‐limiting step generated a sustained level of DA at dopaminergic neurons. Pharmacokinetic studies showed elimination half‐life of l‐DOPA in the plasma after DopAmide treatment of t1/2 = 4.1 h, significantly longer than t1/2 = 2.9 h after treatment with l‐DOPA, consistent with the 6‐OHDA results.ConclusionsThe slow conversion of DopAmide to l‐DOPA provides a sustained level of DA in the dopaminergic cells, shown by the long 6‐OHDA steady rotations. The water solubility and improved bioavailability may help reduce medication frequency associated with l‐DOPA treatment of PD. Sustained levels of DA might lower the super‐sensitization of DA signaling and potentially attenuate l‐DOPA adverse effects.
Can protected areas mitigate the impacts of climate change on bird's species and communities?
Authors: Gaüzère Pierre , Jiguet Frédéric , Devictor Vincent 
Published: February 2016

AbstractAimProtected areas (PAs) are the mainstay of our conservation strategies. While they may succeed in locally preventing species and habitat degradation due to human activities, their ability to mitigate the impacts of climate change on biodiversity is still debated. We assessed whether community and species responses to climate change were related to PAs by testing three main predictions: (1) the thermal adjustment of community composition to temperature changes should be positively related to the proportion of PAs, (2) the species that benefit most from PAs should be less impacted by temperature change, and (3) the species a priori considered the most vulnerable to global change should be even more sensitive to the mitigating effect of PAs.LocationMainland France.MethodsData from a long‐term, large‐scale standardized monitoring programme, recording annual changes in the abundance of 116 breeding bird species in France between 2001 and 2012, were used. Local temporal trends in spring temperature, community reshuffling and bird populations over the country were estimated with a moving window approach (2094 spatial windows). Generalized additive mixed models were then performed to relate these responses to the local proportion of PAs.ResultsMost PAs promote community adjustment to temperature changes. At the species scale, our results show that the more a species benefited from PAs, the less vulnerable it was to temperature changes. PAs were also more effective in mitigating the impact of climate change on the less common and northernmost birds.Main conclusionProtected areas do seem to mitigate climate change impacts on species and communities. Our study argues for the use of integrative frameworks at different biological scales to assess the usefulness and relevance of PAs faced with climate change and suggests that PAs remain key effective conservation strategies in a changing climatic world.
Prognostic factors for cerebral palsy and motor impairment in children born very preterm or very low birthweight: a systematic review
Authors: Linsell Louise , Malouf Reem , Morris Joan , Kurinczuk Jennifer J , Marlow Neil 
Published: February 2016

AimThere is a large literature reporting risk factor analyses for poor neurodevelopment in children born very preterm (VPT: ≤32wks) or very low birthweight (VLBW: ≤1250g), which to date has not been formally summarized. The aim of this paper was to identify prognostic factors for cerebral palsy (CP) and motor impairment in children bornVPT/VLBW.MethodA systematic review was conducted using Medline, Embase, and Pyscinfo databases to identify studies published between 1 January 1990 and 1 June 2014 reporting multivariable prediction models for poor neurodevelopment inVPT/VLBWchildren (registration numberCRD42014006943). Twenty‐eight studies for motor outcomes were identified.ResultsThere was strong evidence that intraventricular haemorrhage and periventricular leukomalacia, and some evidence that the use of postnatal steroids and non‐use of antenatal steroids, were prognostic factors forCP. Male sex and gestational age were of limited use as prognostic factors forCPin cohorts restricted to ≤32 weeks gestation; however, in children older than 5 years with no major disability, there was evidence that male sex was a predictive factor for motor impairment.InterpretationThis review has identified factors which may be of prognostic value forCPand motor impairment inVPT/VLBWchildren and will help to form the basis of future prognostic research.
Utility of combined gray‐scale and perflubutane contrast‐enhanced ultrasound for diagnosing early hepatocellular carcinomas: Comparison of well differentiated and distinctly nodular types
Authors: Tada Toshifumi , Kumada Takashi , Toyoda Hidenori , Sone Yasuhiro , Kaneoka Yuji , Maeda Atsuyuki , Okuda Seiji , Otobe Katsuhiko , Tsuji Nozomi 
Published: February 2016

AimTo clarify the value of gray‐scale ultrasound (US) combined with contrast‐enhanced US (CEUS) with perflubutane in diagnosing early hepatocellular carcinoma (HCC).MethodsA total of 57 surgically resected, well differentiated HCCs were analyzed. Hepatocellular carcinomas were macroscopically diagnosed as vaguely nodular or distinctly nodular types, which correspond to early HCC or progressed HCC, respectively. Gray‐scale US findings were evaluated in terms of shape (round or roundish, or irregular), border and contour (well‐defined and smooth, or poorly defined), and intratumor echo levels (hyper, hypo, iso, heterogeneous, or mosaic). Contrast‐enhanced US findings were evaluated during the arterial phase (vascularity [finely homogeneous, dendritic, or chaotic] and perfusion enhancement [homogeneous or heterogeneous]), portal phase (presence or absence of washout), and post‐vascular phase (echo intensity level [defect, incomplete defect, or iso‐enhancing]).ResultsEighteen HCCs were categorized as early HCCs and the remaining 39 were categorized as progressed HCCs. Receiver operating characteristic curve analysis for the diagnosis of early HCC yielded area under the receiver operating characteristic curve (Az) values for border and contour on gray‐scale US and echo intensity level in the CEUS post‐vascular phase of 0.782 and 0.828, respectively. Multiple logistic regression analysis also indicated that both of these gray‐scale US and CEUS findings were independently associated with early HCC. The Az value for the combination of border and contour and echo intensity for the diagnosis of early HCC was 0.907, corresponding to a high diagnostic value.ConclusionThe combination of gray‐scale US and CEUS can provide high‐quality imaging assessment for diagnosing early HCC.
Comparative study of efficacy, rapidity of detection, and cost‐effectiveness of potassium hydroxide, calcofluor white, and Chicago sky blue stains in the diagnosis of dermatophytoses
Authors: Prakash R. , Prashanth Hosakere Veerappa , Ragunatha Shivanna , Kapoor Meenakshi , Anitha T. K. , Krishnamurthy Veena 
Published: February 2016

AbstractBackgroundThe diagnosis of superficial mycosis such as dermatophytosis is often done clinically. However, in difficult cases, a rapid test with high sensitivity and specificity helps in the immediate confirmation and administration of treatment.MethodsThe efficacy, rapidity of detection, and cost‐effectiveness of KOH preparation, calcofluor white (CW) stain, and Chicago sky blue (CSB) stain in the identification of fungal elements were assessed in patients with dermatophytoses attending the dermatology clinic of a tertiary care hospital. All three tests were performed on each sample collected from 73 patients according to standard procedure. The slides were examined after 5 and 30 minutes in × 10 and × 40 magnifications. The sensitivity and specificity of CW and CSB at 5 and 30 minutes were calculated using KOH preparation as the standard test.ResultsCSB stain showed highest positivity (94.5%) within 5 minutes when compared to KOH (75.3%) and CW (83.5%). After 30 minutes, positivity increased in KOH (84.9%) and CW stains (89%), but it remained the same in CSB stain. Both CW and CSB stains when compared to 10% KOH are equally sensitive (100%), but CW was more specific (72.7%), particularly at 30 minutes. When cost of performing tests on 100 specimens is considered, KOH, CW, and CSB stains cost Rs 5, 100, and 15, respectively.ConclusionCSB stain is a better stain for rapid diagnosis of dermatophytoses because of ease of performance, rapidity of detection, better appreciation of morphology of fungal elements, and cost effectiveness.
Characterization of a new HLA‐A allele, HLA‐A*02:07:08, by cloning and sequencing
Authors: Wang W. Y. , Zhang W. , Li L. X. , Zhu F. M. , Tian W. 
Published: February 2016

SummaryIn this report, we present a novel HLA‐A*02:07 allele, HLA‐A*02:07:08. HLA‐A*02:07:08 was identified in an individual of Han ethnicity in Hunan province, southern China. Following polymerase chain reaction‐sequence‐based typing (PCR‐SBT), this new allele was further confirmed by cloning and sequencing. HLA‐A*02:07:08 differs from HLA‐A*02:07:01 by a single synonymous C to T substitution at nucleotide position 131 in exon 3.
Naringenin targets ERK2 and suppresses UVB‐induced photoaging
Authors: Jung Sung Keun , Ha Su Jeong , Jung Chang Hwa , Kim Yun Tai , Lee Hoo‐Keun , Kim Myoung Ok , Lee Mee‐Hyun , Mottamal Madhusoodanan , Bode Ann M. , Lee Ki Won , Dong Zigang 
Published: February 2016

AbstractA number of natural phytochemicals have anti‐photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase‐1 (MMP‐1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB‐induced MMP‐1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3‐dimensional (3‐D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm2) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB‐induced MMP‐1 expression and AP‐1 activity, and strongly suppressed UVB‐induced phosphorylation of Fos‐related antigen (FRA)‐1 at Ser265. Importantly, UVB irradiation‐induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen‐activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB‐induced extracellular signal‐regulated kinase 2 (ERK2) activity and subsequently attenuated UVB‐induced phosphorylation of p90RSK by competitively binding with ATP. Constitutively active MEK (CA‐MEK) increased FRA1 phosphorylation and expression and also induced MMP‐1 expression, whereas dominant‐negative ERK2 (DN‐ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP‐1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB‐induced wrinkle formation, trans‐epidermal water loss and MMP‐13 expression. Naringenin exerts potent anti‐photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down‐regulation of AP‐1 transactivation and MMP‐1 expression.