bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic association studies in osteoarthritis: is it fairytale?
Authors: Warner Sophie C. , Valdes Ana M. 
Published: October 2016

Purpose of reviewOsteoarthritis is a common complex disorder with a strong genetic component. Other identified risk factors such as increasing age and overweight do not fully explain the risk of osteoarthritis. Here, we highlight the main findings from genetic association studies on osteoarthritis to date.Recent findingsCurrently, genetic association studies have identified 21 independent susceptibility loci for osteoarthritis. Studies have focused on hip, knee and hand osteoarthritis, as well as posttotal joint replacement and minimum joint space width, a proxy for cartilage thickness. Four distinct loci have recently been identified in a genome-wide association scan on minimum joint space width. The role of mitochondrial DNA variants has been the focus of a recent meta-analysis. Findings have previously been mixed, however, this study suggests a plausible involvement of mitochondrial DNA in the progression of radiographic knee osteoarthritis.SummaryIdentifying genetic locations of interest provides a framework upon which to base future studies, for example replication analysis and functional work. Genetic association studies have shaped and will continue to shape research in this field. Improving the understanding of osteoarthritis could improve the diagnosis and treatment of the disease and improve quality of life for many individuals.
Dysfunction of Nucleus Accumbens Is Associated With Psychiatric Problems in Patients With Chronic Low Back Pain
Authors: Kaneko Hideaki , Zhang Shuo , Sekiguchi Miho , Nikaido Takuya , Makita Koshi , Kurata Jiro , Konno Shin-ichi 
Published: October 2016

Study Design.
A cross-sectional study.

Objective.
The aim of this study was to evaluate activity of the nucleus accumbens (NAc) in response to lumbar mechanical stimulation in patients with chronic low back pain (cLBP) using functional magnetic resonance imaging (fMRI).

Summary of Background Data.
Although a modified activity of the NAc was characterized in cLBP patients, its pathological significance has yet to be determined. We hypothesized that NAc activation in response to pain might differ depending on the extent of psychiatric problems, which might be associated with the affective/motivational background of chronic pain.

Methods.
Twenty-one patients with cLBP (four men, 17 women) were recruited. Subjects were divided into two groups on the basis of scores on the patient version of the Brief Scale for Psychiatric problems in Orthopaedic Patients (BS-POP) scores: ≥17 (High Score, HiS group) and <17 (non-High Score, non-HiS group). Each subject was placed in the prone position on a 3-Tesla magnetic resonance imaging (MRI) scanner and stimulated by mechanical stimulation on the left lower back. Three blocks of 30-second pain stimulus calibrated at either 3 or 5 on an 11-grade numerical rating scale (NRS) were applied with intervening 30-second rest conditions during whole-brain echo-planar imaging. Functional images were analyzed using a multisubject general linear model with Bonferroni multiple comparisons.

Results.
Subjects in the HiS group had more intense daily pain and lower quality of life than those in the non-HiS group (P < 0.05). Catastrophic thinking in relation to pain experience did not differ between the groups. Activation at the NAc was smaller in the HiS group than in the non-HiS group (P < 0.001).

Conclusion.
The presence of psychiatric problems was associated with attenuated activity of the NAc in cLBP patients. Dysfunction of the NAc might potentially be involved in the affective/motivational factors in the chronification of LBP.

Level of Evidence. N/A
Painful Cervical Facet Joint Injury Is Accompanied by Changes in the Number of Excitatory and Inhibitory Synapses in the Superficial Dorsal Horn That Differentially Relate to Local Tissue Injury Severity
Authors: Ita Meagan E. , Crosby Nathan D. , Bulka Ben A. , Winkelstein Beth A. 
Published: October 2016

Study Design.
Immunohistochemistry labeled pre- and postsynaptic structural markers to quantify excitatory and inhibitory synapses in the spinal superficial dorsal horn at 14 days after painful facet joint injury in the rat.

Objective.
The objective of this study was to investigate the relationship between pain and synapse density in the spinal cord after facet injury.

Summary of Background Data.
Neck pain is a major contributor to disability and often becomes chronic. The cervical facet joints are susceptible to loading-induced painful injury, initiating spinal central sensitization responses. Although excitatory synapse plasticity has been reported in the superficial dorsal horn early after painful facet injury, whether excitatory and/or inhibitory synapse density is altered at a time when pain is maintained is unknown.

Methods.
Rats underwent either a painful C6/C7 facet joint distraction or sham surgery. Mechanical hyperalgesia was measured and immunohistochemistry techniques for synapse quantification were used to quantify excitatory and inhibitory synapse densities in the superficial dorsal horn at day 14. Logarithmic correlation analyses evaluated whether the severity of facet injury correlated with either behavioral or synaptic outcomes.

Results.
Facet joint injury induces pain that is sustained until day 14 (P <0.001) and both significantly greater excitatory synapse density (P = 0.042) and lower inhibitory synapse density (P = 0.0029) in the superficial dorsal horn at day 14. Injury severity is significantly correlated with pain at days 1 (P = 0.0011) and 14 (P = 0.0002), but only with inhibitory, not excitatory, synapse density (P = 0.0025) at day 14.

Conclusion.
This study demonstrates a role for structural plasticity in both excitatory and inhibitory synapses in the maintenance of facet-mediated joint pain, and that altered inhibitory, but not excitatory, synapse density correlates to the severity of painful joint injury. Understanding the functional consequences of this spinal structural plasticity is critical to elucidate mechanisms of chronic joint pain.

Level of Evidence: N /A
ULTRASOUND MEASUREMENTS OF THE DISTANCE BETWEEN LIMBUS AND RETINAL BREAK IN EYES WITH MEDIA OPACITIES
Authors: Vaiano Agostino S. , Coronado Quitllet Elisabet , Zinzanella Gaetano , De Benedetti Giacomo , Caramello Guido 
Published: October 2016

Purpose:
To assess the reproducibility and accuracy of ultrasound (US) measurements in determining the distance between corneoscleral limbus and retinal break and its relation with the distance measured by indirect ophthalmoscopy, in patients undergoing a laser retinopexy procedure.

Methods:
Forty-four patients with a single retinal break, scheduled for laser a retinopexy procedure (26 phakic patients and 18 pseudophakic patients), underwent 5 repeated measurements by high-resolution US and 3 measurements (at the time of the laser procedure, 1 and 3 months) by indirect ophthalmoscopy with scleral indentation of the corneoscleral limbus-retinal break distance with a caliper.

Results:
In the phakic patients group, measurements ranged from 8.75 mm to 14.45 mm (12.56 ± 1.24, mean ± SD) and from 9.5 mm to 15 mm (12.35 ± 1.32) with US and indirect ophthalmoscopy, respectively. In the pseudophakic patients group, measurements ranged from 9.04 mm to 13.95 mm (11.88 ± 1.33) and from 8.5 mm to 13.2 mm (11.93 ± 0.99) with US and indirect ophthalmoscopy, respectively. The correlation coefficient was greater than 0.97. Measurement variability was very small. In phakic eyes, it was 0.13 ± 0.08 mm and 0.13 ± 0.07 mm with US and indirect ophthalmoscopy, respectively. In pseudophakic eyes, it was 0.12 ± 0.05 mm and 0.14 ± 0.05 mm with US and indirect ophthalmoscopy, respectively. US and indirect ophthalmoscopy measurements were not statistically different (Student's t-test, P = 1.71). The analysis of the variance among phakic and pseudophakic patients confirmed that measurements of the two groups do not differ significantly (Fisher's exact test, P = 0.16). The univariate analysis showed no significant difference in both US and indirect ophthalmoscopy measurements (ANOVA, P = 0.09) and between the two types of measurements and patient groups (ANOVA, P = 0.38).

Conclusion:
This study suggests relevant accuracy and reliability of US readings and provides the possibility of using this technique for localizing tears in eyes with media opacities by identifying the meridian and corneoscleral limbus-retinal break distance.
Efficacy and Safety of Adjunctive Aripiprazole in Schizophrenia
Authors: Zheng Wei , Zheng Ying-Jun , Li Xian-Bin , Tang Yi-Lang , Wang Chuan-Yue , Xiang Ying-Qiang , de Leon Jose 
Published: October 2016

Abstract
This meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of adding aripiprazole to other antipsychotics in schizophrenia. A systematic computer search identified 55 RCTs including 4457 patients who were randomized to aripiprazole (14.0 ± 7.0 mg/d) versus placebo (18 RCTs) or open antipsychotic treatment (37 RCTs). Aripiprazole significantly outperformed the comparison interventions based on psychiatric scales: (1) total score in 43 RCTs (N = 3351) with a standardized mean difference (SMD) of −0.48 (95% confidence interval [CI], −0.68 to −0.28; P < 0.00001; I
2 = 88%), (2) negative symptom score in 30 RCTs (N = 2294) with an SMD of −0.61(95% CI, −0.91 to −0.31; P < 0.00001; I
2 = 91%), and (3) general psychopathology score in 13 RCTs (N = 1138) with a weighted mean difference (WMD) of −4.02 (95% CI, −7.23 to −0.81; P = 0.01; I
2 = 99%), but not in positive symptoms in 29 RCTs (N = 2223) with a SMD of −0.01 (95% CI, 0.26 to 0.25; P = 0.95; I
2 = 88%). Differences in total score based on psychiatric scales may be explained by the use of an antipsychotic for comparison rather than placebo in 31 RCTs with a nonblind design. Aripiprazole outperformed the comparison interventions for body weight in 9 RCTs (N = 505) with a WMD of −5.08 kg (95% CI, −7.14 to −3.02; P < 0.00001; I
2 = 35%) and for body mass index (BMI) in 14 RCTs (N = 809) with a WMD of −1.78 (CI: −2.25 to −1.31; P < 0.00001; I
2 = 54%). The BMI meta-regression analysis indicated aripiprazole's association with lower BMI was stronger in females. Adjunctive aripiprazole appears safe but better RCTs are needed to demonstrate efficacy. Chinese journals and scientific societies should encourage the publication of high-quality RCTs and require registration in a centralized Chinese database.
An Open-Label Pilot Study of Duloxetine in Patients With Irritable Bowel Syndrome and Comorbid Major Depressive Disorder
Authors: Lewis-Fernández Roberto , Lam Peter , Lucak Susan , Galfalvy Hanga , Jackson Elizabeth , Fried Jane , Rosario Melissa , de la Cruz Ana Alicia , Sánchez-Lacay Arturo , Díaz Samantha , Schneier Franklin 
Published: October 2016

Abstract
Major depressive disorder (MDD) and irritable bowel syndrome (IBS) frequently co-occur, yet treating their comorbid presentation is challenging. Low-dose tricyclic antidepressants are efficacious for IBS, but higher doses to treat depressive symptoms present tolerability problems, whereas selective serotonin reuptake inhibitors are more tolerable but show inconsistent efficacy for IBS. If efficacious, serotonin-norepinephrine reuptake inhibitors like duloxetine would provide a useful alternative. We explored efficacy, tolerability, and time to onset of action of duloxetine in comorbid IBS-MDD in an open-label, 12-week trial. Repeated-measures mixed-effects regression analysis with the intent-to-treat sample assessed rate of change of the clinician-administered Gastrointestinal Symptoms Rating Scale, Montgomery-Åsberg Depression Rating Scale, and other clinician-administered and self-report scales. Seventeen Hispanic adults with current MDD and comorbid IBS meeting Rome III criteria entered the study. Medical and laboratory assessment ruled out alarm symptoms and signs inconsistent with IBS. Duloxetine led to significant improvement in Gastrointestinal Symptoms Rating Scale and Montgomery-Åsberg Depression Rating Scale scores and 71.4% and 64.3% intent-to-treat response rates for IBS and MDD, respectively. Abdominal pain severity decreased by 56%. Contrary to expectation of rapid analgesic effects, based on duloxetine studies for neuropathic pain, both IBS and MDD symptoms improved gradually; differences in slopes of improvement were nonsignificant. Duloxetine was moderately well tolerated at a mean endpoint dose of 60 mg/d. Study limitations include the lack of placebo control, modest sample size, single ethnic group, and high attrition rate. Duloxetine efficacy for comorbid IBS-MDD should be studied under placebo-controlled conditions with larger and more diverse samples.
Dihydroxyphenylglycol as a Biomarker of Norepinephrine Transporter Inhibition by Atomoxetine
Authors: Bieck Peter R. , Leibowitz Mark , Lachno D. Richard , Ledent Edouard , Padich Robert , Jhee Stan 
Published: October 2016

Abstract
To assess the primary metabolite of norepinephrine, 3,4-dihydroxyphenylglycol (DHPG), as a sensitive biomarker for norepinephrine transporter (NET) function and the relationship of DHPG measured peripherally and centrally, NET was antagonized with 80 mg/d atomoxetine for 18 days. Twelve healthy subjects were treated with atomoxetine in an open-label, multiple-dose exploratory study. Plasma atomoxetine reached steady state by day 6, and the pharmacokinetic results demonstrated availability of atomoxetine to the central nervous system. The cerebrospinal fluid (CSF)/plasma ratios of atomoxetine based on area under concentration-time curve from 0 to 12 hours postdose (AUC0–12), maximum concentration (Cmax), and predose were 0.3%, 0.2%, and 11%, respectively. Plasma from atomoxetine-treated subjects (ex vivo) significantly inhibited radioligand binding to human NET (P < 0.001) only 1 hour after dosing. Plasma DHPG and DHPG/norepinephrine (ratio) during repeated posture tests were reduced significantly (P < 0.001) on day 5 and stayed significantly reduced up to 1 day after treatment. In CSF, both DHPG and the ratio were significantly reduced (P < 0.001) on day 18. Urine results showed significant decreases for both DHPG and the ratio (P = 0.010 to P < 0.001). Brain-derived neurotrophic factor in CSF was lesser than the limits of detection. The findings suggest that NET blockade can be assessed with DHPG concentration or with the ratio in plasma, CSF, and urine. The data suggest that DHPG is a useful biomarker to proactively assess the pharmacological activity of compounds intended to inhibit NET activity within the brain. The study shows that CSF is a medium for early identification and quantification of biomarkers useful in assessing novel neuroscience targets.
MRI Evidence of Neuropathic Changes in Former College Football Players
Authors: Adler Caleb M. , DelBello Melissa P. , Weber Wade , Williams Miranda , Duran Luis Rodrigo Patino , Fleck David , Boespflug Erin , Eliassen James , Strakowski Stephen M. , Divine Jon 
Published: October 2016

Objective:
To examine effects of participating in collegiate football on neural health several years after retirement. We hypothesized that relative cortical thinning and loss of white matter integrity would be observed in former players.

Design:
Former NCAA Division I football players were compared with demographically similar track-and-field athletes with regard to cortical thickness and white matter integrity.

Setting:
Participants participated in MRI scans at the Center for Imaging Research at the University of Cincinnati.

Participants:
Eleven former football players and 10 demographically similar track-and-field athletes.

Main Outcome Measures:
Normalized cortical thickness was compared between groups using 2-tailed Student t test. As a secondary analysis, Spearman correlation coefficient was calculated between cortical thickness and number of concussions. Fractional anisotropy for regions-of-interest placed in frontal white matter tracts and internal capsule were compared between groups using 2-tailed Student t test.

Results:
Football players showed significantly lower cortical thickness within portions of both the frontal and temporal cortex. Affected frontal regions included left frontal pole and right superior frontal gyrus. Affected temporal regions included portions of the superior temporal gyrus, left inferior temporal gyrus, and right middle and superior temporal gyri. Cortical thickness inversely correlated with number of reported concussions over most of these regions. In addition, fractional anisotropy was lower in the right internal capsule of former football players, relative to controls.

Conclusions:
These findings suggest that at least some consequences of high-level collegiate football play persist even after the cessation of regular head blows. Longer-term studies are warranted to examine potential cognitive and functional implications of sustained cortical atrophy.
Cochlear Implantation in the Elderly: Does Age Matter?
Authors: Rohloff Katharina , Koopmann Mario , Weiß Daniel , Rudack Claudia , Savvas Eleftherios 
Published: October 2016

Objective:
To compare the outcome of hearing rehabilitation in younger versus older adult cochlear implant recipients. Analysis of surgical and postoperative complications, as well as the number of auditory therapy sessions in the two age groups.

Study Design:
Individual retrospective cohort study.

Methods:
A cohort of 145 postlingually deafened adults was evaluated in this study. The patients were divided into two age groups based on the age at implantation: Group I, 18 to 69 years; and Group II, 70 and older. Postoperative hearing performance was measured based on the German Freiburg monosyllabic word test (FM) and the Oldenburg sentence test (OLSA).

Results:
Postoperative hearing evaluation results in both groups plateaued and remained constant after 12 months of implantation. The results remained constant at the 2 and 3-year time intervals. There was a significant difference in complications arising after cochlear implantation. Group II showed more cases of vertigo and dysgeusia. The number of auditory therapy sessions in both groups was similar.

Conclusion:
Cochlear implantation in the elderly is highly effective; the postoperative hearing performance is at the same level as younger adult recipients. Complex hearing tasks, such as hearing in background noise, requires an equally long time for comprehension. The recovery period of vestibular dysfunction after surgery may be longer in the elderly. Auditory therapy rehabilitation is not more time consuming in the elderly compared with the younger counterparts.
Clinical significance of the Scheuer histological staging system for primary biliary cholangitis in Japanese patients
Authors: Namisaki Tadashi , Moriya Kei , Kitade Mitsuteru , Kawaratani Hideto , Takeda Kosuke , Okura Yasushi , Takaya Hiroaki , Nishimura Norihisa , Seki Kenichiro , Kaji Kosuke , Sato Shinya , Sawada Yasuhiko , Yamao Junichi , Mitoro Akira , Uejima Masakazu , Mashitani Tsuyoshi , Shimozato Naotaka , Nakanishi Keisuke , Furukawa Masanori , Saikawa Soichiro , Kubo Takuya , Yoshiji Hitoshi 
Published: October 2016

Background
Inadequate response to ursodeoxycholic acid (UDCA) is associated with unfavorable outcomes in patients with primary biliary cholangitis (PBC). We aimed to identify surrogate markers for predicting long-term prognosis and biochemical response to UDCA in patients with PBC.

Patients and methods
In this single-center, retrospective study, 99 patients with PBC were classified into responders (n=53) and nonresponders (n=46) based on reductions in the γ-glutamyl transpeptidase levels at 1 year after initiating UDCA therapy (Nara criteria). We assessed whether the criteria for patentability by different countries are useful in predicting the prognosis of PBC. The accuracy of Scheuer and Nakanuma staging systems in predicting prognosis and treatment response was compared.

Results
Nara definition had comparable utility to the Paris-II definition for selecting patients in whom UDCA monotherapy can be safely continued. Patients at Scheuer stage 1 had a significantly better prognosis than those at Scheuer stages 3 or 4 (P<0.05 and 0.0001, respectively). Patients at Nakanuma stage 4 had decreased survival compared with those at stage 1 (P<0.05). The proportion of responders to nonresponders was significantly higher in stages 1–3 PBC than in stage 4 PBC, according to both staging systems (P<0.05 for both). All patients with Scheuer stage 4 PBC were nonresponders, whereas only 28.6% (2/7) of those with Nakanuma stage 4 PBC were responders.

Conclusion
The Scheuer staging system had greater utility in predicting long-term prognosis and UDCA response than the Nakanuma staging system.
Truths and controversies concerning the role of miRNAs in atherosclerosis and lipid metabolism
Authors: Baldán Ángel , Fernández-Hernando Carlos 
Published: October 2016

Purpose of review
Better tools are sorely needed for both the prevention and treatment of cardiovascular diseases, which account for more than one-third of the deaths in Western countries. MicroRNAs typically regulate the expression of several mRNAs involved in the same biological process. Therapeutic manipulation of miRNAs could restore the expression of multiple players within the same physiologic pathway, and ideally offer better curative outcomes than conventional approaches that target only one single player within the pathway. This review summarizes available studies on the prospective value of targeting miRNAs to prevent dyslipidemia and atherogenesis.

Recent findings
Silencing the expression of miRNAs that target key genes involved in lipoprotein metabolism in vivo with antisense oligonucleotides results in the expected de-repression of target mRNAs in liver and atherosclerotic plaques. However, the consequences of long-term antimiRNA treatment on both circulating lipoproteins and athero-protection are yet to be established.

Summary
A number of studies have demonstrated the efficacy of miRNA mimics and inhibitors as novel therapeutic tools for treating dyslipidemia and cardiovascular diseases. Nevertheless, concerns over unanticipated side-effects related to de-repression of additional targets should not be overlooked for miRNA-based therapies.