bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital Heart Defects and Indices of Placental and Fetal Growth in a Nationwide Study of 924 422 Liveborn Infants
Authors: Matthiesen Niels B. , Henriksen Tine B. , Agergaard Peter , Gaynor J. William , Bach Cathrine C. , Hjortdal Vibeke E. , Østergaard John R. 
Published: October 2016

Background:
Congenital heart defects (CHDs) have been associated with placental anomalies. The nature and the consequences of this association remain poorly understood. We aimed to estimate the associations between all major subtypes of CHD and placental weight at birth, and the association between placental weight and measures of both overall and cerebral growth in fetuses with CHD, as well.

Methods:

We included all 924 422 liveborn Danish singletons, 1997 to 2011. CHD was present in 7569. We compared mean differences in placental weight
z
score between newborns with CHD and newborns without CHD by multivariable linear regression adjusted for potential confounders.

Results:

CHD was associated with a mean
z
score difference of –0.04 (95% confidence interval, –0.07 to –0.02). Some subtypes were associated with smaller placental size at birth: tetralogy of Fallot, –0.45 (95% confidence interval, –0.58 to –0.31); double-outlet right ventricle, –0.48 (95% confidence interval, –0.87 to –0.10); major ventricular septal defects, –0.41 (95% confidence interval, –0.52 to –0.29). Placental weight
z
score was associated with birth weight and head circumference
z
scores in all subtypes. In the 3 mentioned subtypes, the mean deviations from the population mean head circumference and birth weight
z
scores were reduced by up to 66% with adjustment for placental weight
z
score.

Conclusions:

Three subtypes of CHD were associated with lower placental weight, and placental weight was associated with measures of both overall growth and cerebral growth in fetuses with all subtypes of CHD. In certain subtypes, the described deviations in fetal growth were reduced by up to two-thirds after adjustment for placental weight
z
score.
Sex Differences in Financial Barriers and the Relationship to Recovery After Acute Myocardial Infarction
Authors: Beckman Adam L. , Bucholz Emily M. , Zhang Weiwei , Xu Xiao , Dreyer Rachel P. , Strait Kelly M. , Spertus John A. , Krumholz Harlan M. , Spatz Erica S. 
Published: October 2016

Background

Financial barriers to health care are associated with worse outcomes following acute myocardial infarction (
AMI
). Yet, it is unknown whether the prevalence of financial barriers and their relationship with post‐
AMI
outcomes vary by sex among young adults.

Methods and Results

We assessed sex differences in patient‐reported financial barriers among adults aged <55 years with
AMI
using data from the Variation in Recovery: Role of Gender on Outcomes of Young
AMI
Patients study. We examined the prevalence of financial barriers and their association with health status 12 months post‐
AMI
. Among 3437 patients, more women than men reported financial barriers to medications (22.3% vs 17.2%;
P
=0.001), but rates of financial barriers to services were similar (31.3% vs 28.9%;
P
=0.152). In multivariable linear regression models adjusting for baseline health, psychosocial status, and clinical characteristics, compared with no financial barriers, women and men with financial barriers to services and medications had worse mental functional status (Short Form‐12 mental health score: mean difference [
MD
]=−3.28 and −3.35, respectively), greater depressive symptomatology (Patient Health Questionnaire‐9:
MD,
2.18 and 2.16), lower quality of life (Seattle Angina Questionnaire–Quality of Life:
MD
, −4.98 and −7.66), and higher perceived stress (Perceived Stress Score:
MD
, 3.76 and 3.90; all
P
<0.05). There was no interaction between sex and financial barriers.

Conclusions

Financial barriers to care are common in young patients with
AMI
and associated with worse health outcomes 1 year post‐
AMI
. Whereas women experienced more financial barriers than men, the association did not vary by sex. These findings emphasize the importance of addressing financial barriers to recovery post‐
AMI
in young adults.
Chemerin Elicits Potent Constrictor Actions via Chemokine‐Like Receptor 1 (CMKLR1), not G‐Protein‐Coupled Receptor 1 (GPR1), in Human and Rat Vasculature
Authors: Kennedy Amanda J. , Yang Peiran , Read Cai , Kuc Rhoda E. , Yang Lucy , Taylor Emily J. A. , Taylor Colin W. , Maguire Janet J. , Davenport Anthony P. 
Published: October 2016

Background

Circulating levels of chemerin are significantly higher in hypertensive patients and positively correlate with blood pressure. Chemerin activates chemokine‐like receptor 1 (
CMKLR
1 or ChemR23) and is proposed to activate the “orphan” G‐protein‐coupled receptor 1 (
GPR
1), which has been linked with hypertension. Our aim was to localize chemerin,
CMKLR
1, and
GPR
1 in the human vasculature and determine whether 1 or both of these receptors mediate vasoconstriction.

Methods and Results

Using immunohistochemistry and molecular biology in conduit arteries and veins and resistance vessels, we localized chemerin to endothelium, smooth muscle, and adventitia and found that
CMKLR
1 and
GPR
1 were widely expressed in smooth muscle. C9 (chemerin149–157) contracted human saphenous vein (
pD
2
=7.30±0.31) and resistance arteries (
pD
2
=7.05±0.54) and increased blood pressure in rats by 9.1±1.0 mm Hg at 200 nmol. Crucially, these in vitro and in vivo vascular actions were blocked by
CCX
832, which we confirmed to be highly selective for
CMKLR
1 over
GPR
1. C9 inhibited
cAMP
accumulation in human aortic smooth muscle cells and preconstricted rat aorta, consistent with the observed vasoconstrictor action. Downstream signaling was explored further and, compared to chemerin, C9 showed a bias factor=≈5000 for the G
i
protein pathway, suggesting that
CMKLR
1 exhibits biased agonism.

Conclusions

Our data suggest that chemerin acts at
CMKLR
1, but not
GPR
1, to increase blood pressure. Chemerin has an established detrimental role in metabolic syndrome, and these direct vascular actions may contribute to hypertension, an additional risk factor for cardiovascular disease. This study provides proof of principle for the therapeutic potential of selective
CMKLR
1 antagonists.
The prevalence of metabolic syndrome increases with serum high sensitivity C-reactive protein concentration in individuals without a history of cardiovascular disease: a report from a large Persian cohort
Authors: Kazemi-Bajestani Seyyed MR , Tayefi Maryam , Ebrahimi Mahmoud , Heidari-Bakavoli Ali R , Moohebati Mohsen , Parizadeh Seyyed MR , Esmaeili Habibollah , Ferns Gordon AA , Ghayour-Mobarhan Majid 
Published: October 2016

Background Metabolic syndrome is defined by a clustering of cardiovascular risk factors and is associated with a heightened inflammatory state. A raised serum high-sensitivity C-reactive protein, a marker of inflammation, is also known to associate with cardiovascular risk. We have investigated the relationship between the presence of metabolic syndrome and serum high-sensitivity C-reactive protein concentration in a large representative Persian population cohort without a history of cardiovascular disease. Methods The MASHAD study population cohort comprised 9778 subjects, who were recruited from the city of Mashhad, Iran, between 2007 and 2008. Several cardiovascular risk factors were measured in this population without cardiovascular disease. Individuals were categorized into quartiles of serum high-sensitivity C-reactive protein concentration: first quartile – 0.72 (0.59–0.85) (median [range]) mg/L, second quartile – 1.30 (1.14–1.4) mg/L, third quartile – 2.29 (1.92–2.81) mg/L and fourth quartile – 6.63 (4.61–11.95) mg/L, respectively. The prevalence of metabolic syndrome in each quartile was determined using either International Diabetes Federation or Adult Treatment Panel III criteria. Results The prevalence of metabolic syndrome was highest in the fourth quartile for serum high-sensitivity C-reactive protein (1220 subjects [50.0%]), and significantly higher than that in the first quartile (reference group) (634 subjects [25.9%]) ( P < 0.001). A positive smoking habit (OR, 1.47 [1.26–1.70], P < 0.001) and the presence of either metabolic syndrome-International Diabetes Federation (OR, 1.35 [1.18–1.55], P < 0.001) or metabolic syndrome-ATPIII (OR, 1.40 [1.18–1.50], P < 0.001) were strong predictors of a fourth quartile for serum high-sensitivity C-reactive protein concentration. Conclusions There was a significant association between high concentrations of serum high-sensitivity C-reactive protein and the presence of metabolic syndrome among individuals without a history of cardiovascular disease in our Persian cohort.
The role of calculated non-caeruloplasmin-bound copper in Wilson’s disease
Authors: Duncan Andrew , Yacoubian Calum , Beetham Robert , Catchpole Anthony , Bullock David 
Published: October 2016

Background US and European guidelines suggest the use of calculated non-caeruloplasmin-bound copper (free copper index) for the diagnosis and management of Wilson’s Disease. However, there is concern that the required analytical measurements of caeruloplasmin and copper may not be sufficiently robust at the concentrations usually found. Methods Aliquots of six plasma specimens were sent to laboratories participating in the UK National External Quality Assessment Scheme for copper and caeruloplasmin. The variability of these two reported measurements and the calculated non-caeruloplasmin-bound copper concentrations were compared. The variability of caeruloplasmin reference ranges quoted by laboratories was also investigated. Results No laboratories use the required enzymatic methods in the calculation of non-caeruloplasmin-bound copper. The interlaboratory variations in caeruloplasmin concentrations and calculated non-caeruloplasmin-bound copper concentrations were very considerable so making clinical interpretation unreliable. Wide differences in the caeruloplasmin reference ranges used were also found. Conclusions Such variations of the calculated non-caeruloplasmin-bound copper concentrations and the predominant use of immunological methods for measuring caeruloplasmin preclude a clinical role for this calculated value in the investigation of Wilson’s disease.
Vitamin D-binding protein as it is understood in 2016: is it a critical key with which to help to solve the calcitriol conundrum?
Authors: Davey RX 
Published: October 2016

Background The misnamed ‘vitamin’ D is actually the hormone calcitriol (1,25 dihydroxyhydroxyvitamin D). It has a central regulatory role in calcium metabolism, and more widely in the immune system. The prohormone calcifediol (25 hydroxyvitamin D) is more easily measured in the laboratory and is the analyte used in reference interval formulation. Being highly lipid soluble, both calcifediol and calcitriol travel in the bloodstream on carriage proteins, principally on vitamin D-binding protein. Summary This review reports our current understanding of vitamin D-binding protein. Its genetic determinants and their effect on it and secondarily on calcifediol concentrations and assays are described. Its complex interplay with parathyroid hormone is considered. The analytical state of the art is translated into the challenge it imposes clinically, in the formulation of reference intervals and in their use in advising and managing patients. Several recent challenges thrown up to laboratories by percipient clinicians highlight the dilemma vitamin D-binding protein poses. A way forward is suggested.
An ISBD perspective on the sociocultural challenges of managing bipolar disorder: A content analysis
Authors: Oedegaard Christine H , Berk Lesley , Berk Michael ,   International Society for Bipolar Disorders (ISBD) Transcultural Task Force, Youngstrom Eric A , Dilsaver Steven C , Belmaker Robert H , Oedegaard Ketil J , Fasmer Ole B , Engebretsen Ingunn M 
Published: October 2016

Objective: Clinical management of bipolar disorder patients might be affected by culture and is further dependent on the context of healthcare delivery. There is a need to understand how healthcare best can be delivered in various systems and cultures. The objective of this qualitative study was to gain knowledge about culture-specific values, beliefs and practices in the medical care provided to patients with bipolar disorders from a provider perspective in various areas of the world. Sampling and methods: The International Society for Bipolar Disorders (ISBD) network provided the framework for this qualitative study. An electronic interview with open-ended questions was administered to 19 international experts on bipolar spectrum disorder representing the International Society for Bipolar Disorders chapter network in 16 countries and six continents. In addition, there were two in-depth interviews with bipolar spectrum disorder experts done prior to the survey. The data were analysed using content analysis, and the information was structured using the software NVivo by QSR International Pty Ltd. Findings: All participants described sociocultural factors as important in healthcare delivery to bipolar patients in their part of the world, both in accessing healthcare and in providing culturally appropriate care. Factors that affected the provider’s ability to supply good clinical management of patients were access to treatment options and long-term follow-up, as well as general strategies to combat stigma. In some societies, the patients’ use of alternative treatments, gender issues and religion were also important factors. Understanding the impact of such culturally specific factors was overall regarded as essential for proper treatment interventions. Conclusion: Sociocultural factors clearly affect the nature and quality of medical services delivered to bipolar patients. Financial, social and cultural factors affect patients’ health-seeking behaviour, and this highlights the need for knowledge about such factors in order to adequately identify and treat bipolar patients globally. Culturally adapted training and psychoeducation programmes are particularly warranted.
Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: a randomized controlled trial
Authors: Fujimaki Yoko , Tsunoda Koichi , Kobayashi Rika , Tonghyo Chong , Tanaka Fujinobu , Kuroda Hiroyuki , Numata Tsutomu , Ishii Toyota , Kuroda Reiko , Masuda Sawako , Hashimoto Sho , Misawa Hayato , Shindo Naoko , Mori Takahiro , Mori Hiroko , Uchiyama Naoki , Kamei Yuichirou , Tanaka Masashi , Hamaya Hironobu , Funatsuki Shingo , Usui Satoko , Ito Ikuno , Hamada Kohei , Shindo Akihito , Tokumaru Yutaka , Morita Yoko , Ueha Rumi , Nito Takaharu , Kikuta Shu , Sekimoto Sotaro , Kondo Kenji , Sakamoto Takashi , Itoh Kenji , Yamasoba Tatsuya , Matsumoto Sumio ,   Research Group for Aspiration Pneumonia, National Hospital Organization, Japan
Published: October 2016

Objectives: To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. Design: Parallel-arm, individual randomized controlled trial. Methods: Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. Results: Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). Conclusion: The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. Clinical Trial.gov Identifier-UMIN000015567
In vivo variation in same-day estimates of metabotropic glutamate receptor subtype 5 binding using [11C]ABP688 and [18F]FPEB
Authors: DeLorenzo Christine , Gallezot Jean-Dominique , Gardus John , Yang Jie , Planeta Beata , Nabulsi Nabeel , Ogden R Todd , Labaree David C , Huang Yiyun H , Mann J John , Gasparini Fabrizio , Lin Xin , Javitch Jonathan A , Parsey Ramin V , Carson Richard E , Esterlis Irina 
Published: October 2016

Positron emission tomography tracers [11C]ABP688 and [18F]FPEB target the metabotropic glutamate receptor subtype 5 providing quantification of the brain glutamatergic system in vivo. Previous [11C]ABP688 positron emission tomography human test–retest studies indicate that, when performed on the same day, significant binding increases are observed; however, little deviation is reported when scans are >7 days apart. Due to the small cohorts examined previously (eight and five males, respectively), we aimed to replicate the same-day test–retest studies in a larger cohort including both males and females. Results confirmed large within-subject binding differences (ranging from −23% to 108%), suggesting that measurements are greatly affected by study design. We further investigated whether this phenomenon was specific to [11C]ABP688. Using [18F]FPEB and methodology that accounts for residual radioactivity from the test scan, four subjects were scanned twice on the same day. In these subjects, binding estimates increased between 5% and 39% between scans. Consistent with [11C]ABP688, mean absolute test–retest variability was previously reported as <12% when scans were >21 days apart. This replication study and pilot extension to [18F]FPEB suggest that observed within-day binding variation may be due to characteristics of mGluR5; for example, diurnal variation in mGluR5 may affect measurement of this receptor.
Reappraisal of the reference levels for energy metabolites in the extracellular fluid of the human brain
Authors: Sánchez-Guerrero Angela , Mur-Bonet Gemma , Vidal-Jorge Marian , Gándara-Sabatini Darío , Chocrón Ivette , Cordero Esteban , Poca Maria-Antonia , Mullen Katharine , Sahuquillo Juan 
Published: October 2016

Cerebral microdialysis is widely used in neurocritical care units. The goal of this study was to establish the reference interval for the interstitial fluid concentrations of energy metabolites and glycerol by using the extrapolation to zero-flow methodology in anesthetized patients and by constant perfusion at 0.3 µL/min in awake patients. A CMA-71 probe was implanted during surgery in normal white matter of patients with posterior fossa or supratentorial lesions, and the perfusion flow rate was randomized to 0.1, 0.3, 0.6, 1.2, and 2.4 µL/min. Within 24 h of surgery, perfusion was restarted at a constant 0.3 µL/min in fully awake patients. The actual interstitial fluid metabolite concentrations were calculated using the zero-flow methodology. In vitro experiments were also conducted to evaluate the reproducibility of the in vivo methodology. Nineteen patients (seven males) with a median age of 44 years (range: 21–69) were included in the in vivo study. The median (lower–upper) reference interval values were 1.57 (1.15–4.13 mmol/L) for glucose, 2.01 (1.30–5.31 mmol/L) for lactate, 80.0 (54.4–197.0 µmol/L) for pyruvate, and 49.9 (23.6–227.3 µmol/L) for glycerol. The reference intervals reported raises the need to reconsider traditional definitions of brain metabolic disturbances and emphasize the importance of using different thresholds for awake patients and patients under anesthesia.
Oral delivery of human growth hormone: Preparation, characterization, and pharmacokinetics
Authors: Shi Yanan , Li Keke , Tian Baocheng , Xu Maolei , Lv Qingzhi , Zhao Juanjuan , Han Jingtian , Feng Dongxiao 
Published: October 2016

Daily subcutaneous injection of human growth hormone has been used for the treatment of growth hormone deficiency and growth failure but has led to poor patient compliance and renal toxicity. Thus, it is crucial to develop favorable growth hormone delivery systems to improve patient compliance. In the present study, to increase the oral bioavailability of growth hormone and improve patient compliance, enteric-coated capsules filled with monomethoxyl poly(ethylene glycol)-b-poly(L-lactide-co-glycolide) nanoparticles were prepared to facilitate oral growth hormone delivery. The nanoparticles were less than 100 nm in size, exhibited narrow polydispersity indices < 0.3, and showed a zeta potential of −4.87 mV. The highest efficiency of growth hormone encapsulation achieved in this study was nearly 70%. An in vitro release experiment showed that adequate amounts of growth hormone were retained under simulated gastric conditions and significant amounts of growth hormone were released under simulated intestinal conditions. The bioavailability of encapsulated growth hormone relative to subcutaneously injected growth hormone in Sprague-Dawley rats was 11.06%. Thus, the use of poly(ethylene glycol)-b-poly(L-lactide-co-glycolide) nanoparticles yielded promising results, and these agents should be investigated further regarding their potential as an oral growth hormone delivery system in the future.
Statistical analysis plan of the head position in acute ischemic stroke trial pilot (HEADPOST pilot)
Authors: Olavarría Verónica V , Arima Hisatomi , Anderson Craig S , Brunser Alejandro , Muñoz-Venturelli Paula , Billot Laurent , Lavados Pablo M ,   for the HEADPOST Pilot Investigators
Published: October 2016

Background The HEADPOST Pilot is a proof-of-concept, open, prospective, multicenter, international, cluster randomized, phase IIb controlled trial, with masked outcome assessment. The trial will test if lying flat head position initiated in patients within 12 h of onset of acute ischemic stroke involving the anterior circulation increases cerebral blood flow in the middle cerebral arteries, as measured by transcranial Doppler. The study will also assess the safety and feasibility of patients lying flat for ≥24 h. The trial was conducted in centers in three countries, with ability to perform early transcranial Doppler. A feature of this trial was that patients were randomized to a certain position according to the month of admission to hospital. Objective To outline in detail the predetermined statistical analysis plan for HEADPOST Pilot study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with comparisons made between randomized groups. For the outcomes, statistical comparisons to be made between groups are planned and described. Results This statistical analysis plan was developed for the analysis of the results of the HEADPOST Pilot study to be transparent, available, verifiable, and predetermined before data lock. Conclusions We have developed a statistical analysis plan for the HEADPOST Pilot study which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. Trial registration The study is registered under HEADPOST-Pilot, ClinicalTrials.gov Identifier NCT01706094.