bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zolpidem and eszopiclone prime α1β2γ2 GABAA receptors for longer duration of activity
Authors: Dixon Christine L , Harrison Neil L , Lynch Joseph W , Keramidas Angelo 
Published: March 2015

Background and PurposeGABAA receptors mediate neuronal inhibition in the brain. They are the primary targets for benzodiazepines, which are widely used to treat neurological disorders including anxiety, epilepsy and insomnia. The mechanism by which benzodiazepines enhance GABAA receptor activity has been extensively studied, but there is little mechanistic information on how non‐benzodiazepine drugs that bind to the same site exert their effects. Eszopiclone and zolpidem are two non‐benzodiazepine drugs for which no mechanism of action has yet been proposed, despite their clinical importance as sleeping aids. Here we investigate how both drugs enhance the activity of α1β2γ2 GABAA receptors.Experimental ApproachWe used rapid ligand application onto macropatches and single‐channel kinetic analysis to assess rates of current deactivation. We also studied synaptic currents in primary neuronal cultures and in heterosynapses, whereby native GABAergic nerve terminals form synapses with HEK293 cells expressing α1β2γ2 GABAA receptors. Drug binding and modulation was quantified with the aid of an activation mechanism.Key ResultsAt the single‐channel level, the drugs prolonged the duration of receptor activation, with similar KD values of ∼80 nM. Channel activation was prolonged primarily by increasing the equilibrium constant between two connected shut states that precede channel opening.Conclusions and ImplicationsAs the derived mechanism successfully simulated the effects of eszopiclone and zolpidem on ensemble currents, we propose it as the definitive mechanism accounting for the effects of both drugs. Importantly, eszopiclone and zolpidem enhanced GABAA receptor currents via a mechanism that differs from that proposed for benzodiazepines.
Review: Comprehensive treatments for youth comorbidity – evidence‐guided approaches to a complicated problem
Authors: Bearman Sarah Kate , Weisz John R. 
Published: March 2015

BackgroundEvidence‐based treatments (EBTs) with a single‐disorder focus have improved the potential for youth mental health care, yet may be an imperfect fit to clinical care settings where diagnostic comorbidity and co‐occurring problems are commonplace. Most EBTs were developed to treat one diagnosis or problem (or a small homogenous cluster), but most clinically referred youths present with multiple disorders and problems.FindingsThree emerging approaches may help address the comorbidity that is so common in treated youths. Conceptually unified treatments target presumed causal and maintaining factors that are shared among more than one disorder or problem area; preliminary open trials and case studies show promising results. Modular protocols combine the ‘practice elements’ that commonly appear in separate single‐disorder EBTs and repackage them into coordinated delivery systems; one modular protocol, MATCH, has produced positive findings in a randomized effectiveness trial. Monitoring and Feedback Systems (MFSs) provide real‐time data on client progress to inform clinical decision‐making, encompassing comorbid and co‐occurring problems; one study shows beneficial effects in everyday practice with diverse youth problems.ConclusionsAll three approaches – conceptually unified, modular, and MFS – can be strengthened by increased research attention to treatment integrity, clinician user‐appeal, design simplicity, and the infrastructure necessary for successful implementation.
Clinical presentation in insulinoma predicts histopathological tumour characteristics
Authors: Wolf Peter , Winhofer Yvonne , Smajis Sabina , Anderwald Christian‐Heinz , Scheuba Christian , Niederle Bruno , Gessl Alois , Luger Anton , Krebs Michael , Koperek Oskar 
Published: March 2015

SummaryBackgroundInsulinomas are rare neuroendocrine tumours (NETs) of the pancreas, characterized clinically by neuroglycopenic symptoms during periods of substrate deficiency. The gold standard test for diagnosing an insulinoma is a 72‐h fast. However, the prognostic value of parameters in the standardized 72‐h fast on histopathological tumour criteria and clinical presentation has not been examined.MethodsIn thirty‐three patients diagnosed with an insulinoma records, and data were investigated retrospectively. Histopathological tumour characteristics, including staging, grading and size, were reviewed. Grading was performed using Ki‐67 index. Cut‐off values for classical grading (Gclas) were set at G1clas≤2%, G2clas3–20% & G3clas>20% and for modified grading (Gmod) at G1mod<5%, G2mod5–20% & G3mod>20%.ResultsWhen Gmod criteria were applied, the initial blood glucose was lower in GII/IIImod patients compared to GImod (2·8 ± 0·8 vs 3·8 ± 1·3 mmol/l; P = 0·046). Basal and end of fast levels of insulin (basal insulin 71 ± 61 vs 20 ± 16 mU/l; P < 0·001; end of fast insulin 77 ± 51 vs 21 ± 20 mU/l; P < 0·001) and c‐peptide (basal c‐peptide 5·4 ± 2·4 vs 2·7 ± 1·6 μg/l; P = 0·004; end of fast c‐peptide 5·3 ± 2·4 vs 2·5 ± 1·4 μg/l; P = 0·001) were significantly higher in GII/IIImod than in GImod. No differences between the groups were observed when Gclas criteria were applied. Additionally, close correlations were observed between insulin concentration, Ki‐67 index and tumour size.ConclusionThis study shows an impact of histopathological tumour characteristics in patients suffering from an insulinoma on clinical presentation during a standardized 72‐h fast. Lower initial blood glucose levels and higher concentrations of insulin and c‐peptide are associated with worse tumour grading and larger tumour size.
The risk of osteoporosis in patients with liver cirrhosis: a meta‐analysis of literature studies
Authors: Lupoli Roberta , Di Minno Alessandro , Spadarella Gaia , Ambrosino Pasquale , Panico Annalisa , Tarantino Luciano , Lupoli Gelsy , Lupoli Giovanni , Di Minno Matteo Nicola Dario 
Published: March 2015

SummaryObjectiveData about the association between cirrhosis and osteoporosis are contrasting. Thus, we have performed a meta‐analysis of literature studies on this topic.DesignMEDLINE, Cochrane library, EMBASE, Scopus and Web of Science databases have been searched to retrieve all articles of interest. Data on prevalence of osteoporosis, bone mineral density (BMD) and bone turnover laboratory parameters were compared among cirrhotic patients and control subjects without cirrhosis.PatientsStudies on patients with liver cirrhosis screened for the presence of osteoporosis were included.ResultsSix case–control studies (372 cirrhotic patients and 1579 controls) were included. The prevalence of osteoporosis was higher in cirrhotic patients than in controls (34·7% vs 12·8%, OR: 2·52, 95%CI: 1·11, 5·69; P = 0·03, I2 = 81%; P = 0·005). Accordingly, a reduced lumbar spine BMD (MD: −0·13, 95%CI: −0·24, −0·02; P = 0·02, I2 = 93%; P < 0·00001) and z‐score (MD: −1·06, 95%CI: −1·79, −0·34; P = 0·004, I2 = 95%; P < 0·00001) were found in cirrhotic patients as compared with controls. In contrast, no significant differences were reported in femoral neck BMD and z‐score.Interestingly, bone turnover laboratory parameters widely confirmed these results showing higher levels of ALP and D‐Pyr, accompanied by reduced levels of IGF‐1, PTH and 25‐OH‐D in cirrhotic patients as compared with controls.ConclusionsDespite the high heterogeneity among studies, data showed an increased prevalence of osteoporosis in patients with cirrhosis. This information suggests the need of an accurate screening of bone mineral density in patients with liver cirrhosis to plan an adequate osteoporosis management.
Professionals' perceptions of the rocky routes to successful outcomes for young people in a children's residential school
Authors: Syme Audrey , Hill Malcolm 
Published: March 2015

AbstractPoor outcomes for young people in and leaving care have been well documented and research has indicated that the expectations of professionals working with children and young people looked after is a significant influence, particularly in relation to education. An evaluation of an independent children's residential school in Scotland provided a rare opportunity to analyse and compare the views of different kinds of staff about desirable outcomes and how successful outcomes could be achieved. Care workers, teachers and specialist support staff shared some views, but also held contrasting expectations, which appeared to be linked to differing emphases in their models for working with young people. This paper offers tentative explanations for such differences and concludes with suggestions on how to help align service staffs' expectations of young people leaving their care.
Sequential healing events of osseointegration at UnicCa® and SLActive® implant surfaces: an experimental study in the dog
Authors: Favero Riccardo , Lang Niklaus P. , Salata Luiz A. , Neto Evandro Carneiro Martins , Caroprese Marino , Botticelli Daniele 
Published: March 2015

AbstractAimTo study the sequential events in osseointegration at implants with highly hydrophilic surfaces.Material and methodsAll premolars and the first molars were bilaterally extracted in 12 Beagle dogs. After 3 months, full‐thickness flaps were elevated and two different implants systems with various surfaces were randomly installed in the edentulous premolar region in one side of the mandible. One surface was acid etched and further modified with calcium ions (UnicCa®), while the other was sandblasted with large grits and acid etched (SLActive®). The flaps were sutured to allow a fully submerged healing. The surgery on the other side of the mandible and the sacrifices were planned in such a way to obtain biopsies representing the healing after 1, 2, 4, and 8 weeks (n = 6 per period).ResultsAfter one week of healing, new bone apposition was found at both surfaces with percentages of 6.9 ± 3.3% and 6.1 ± 4.6% at UnicCa® and SLActive®, respectively. After 2 weeks, the percentages had increased to 29.1 ± 11.9% and 21.6 ± 14.3%, respectively. After 4 and 8 weeks of healing, mean values of 46.3 ± 7.3% and 58.7 ± 15.1% at UnicCa® and 51.2 ± 16.1% and 68.9 ± 15.4% at SLActive® surfaces were found, respectively. None of the differences in percentages were statistically significant. Concomitantly, the old bone was resorbed at both surfaces from about 21–22% after 1 week to about 4–6% after 8 weeks of healing.ConclusionsThe osseointegration process onto moderately rough titanium implant surfaces of high hydrophilicity was very similar for two implant systems that were both nanotechnologically modified.
Glove use among hairdressers: difficulties in the correct use of gloves among hairdressers and the effect of education
Authors: Oreskov Katia W. , Søsted Heidi , Johansen Jeanne D. 
Published: March 2015

SummaryBackgroundHand eczema is frequent among Danish hairdressers, and they are advised to use gloves as protection. However, studies indicate that a significant proportion use gloves inappropriately.ObjectivesTo determine whether hairdressers and apprentices use protective gloves in the correct way, and to determine whether a demonstration of correct use could cause an improvement.MethodsForty‐three hairdressers and apprentices were asked to perform a hair wash while wearing gloves. The shampoo used was contaminated with an ultraviolet (UV) trace material. Two rounds of hair washing were carried out by each person, interrupted by a demonstration of how to use gloves correctly. Photographs were taken to compare UV contamination before and after the demonstration.ResultsAll of the participants (100%) had their hands contaminated during the first round; the area ranged between 0.02 and 101.37 cm2 (median 3.62 cm2). In the second round, 55.8% were contaminated (range 0.00–3.08 cm2; median 0.01 cm2). The reduction in contaminated skin areas was statistically significant (p < 0.001), proving an effect of the glove demonstration. There were no significant differences between hairdressers and apprentices.ConclusionsHairdressers and apprentices lack knowledge on how to handle gloves correctly. A short demonstration of correct glove use made a significant difference in the skin protection provided by gloves.
MicroRNA‐93 regulates collagen loss by targeting MMP3 in human nucleus pulposus cells
Authors: Jing Wanli , Jiang Wenxue 
Published: March 2015

AbstractObjectivesDegenerated disc disease is one of the most common medical conditions in patients suffering from low back pain. Recent studies have shown that microRNAs can regulate cell function in many pathological conditions. The aim of this study was to investigate expression and role of miR‐93 in disc degeneration.Materials and methodsQuantitative RT‐PCR was employed to investigate level of miR‐93 in degenerative nucleus pulposus (NP) tissues. Then, functional analysis of miR‐93 in regulating collagen II expression was performed. Subsequently, western blotting and luciferase reporter assay were used to detect the target gene.ResultsWe showed that miR‐93 was significantly down‐regulated in degenerative NP tissues and its levels were associated with grade of disc degeneration. Overexpression of miR‐93 stimulated type II collagen expression in NP cells. Moreover, MMP3 was identified as a putative target of miR‐93. MiR‐93 inhibited MMP3 expression by directly targeting its 3′UTR, and this was abolished by miR‐93 binding site mutations. Additionally, restoration of MMP3 in miR‐93‐overexpressed NP cells reversed effects of type II collagen expression. Expression of MMP3 inversely correlated with miR‐93 expression in degenerative NP tissues.ConclusionsTaken together, we demonstrated that miR‐93 contributed to abnormal NP cell type II collagen expression by targeting MMP3, involved in intervertebral disc degeneration.
miR‐709 up‐regulated in hepatocellular carcinoma, promotes proliferation and invasion by targeting GPC5
Authors: Liu Tonggang , Zhang Xuezhong , Sha Kaihui , Liu Xianxian , Zhang Liguo , Wang Bangmao 
Published: March 2015

AbstractObjectivesHepatocellular carcinoma (HCC) is one of the most common cancers and is a significant leading cause of cancer‐related deaths worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with cancer development and progression. However, up to now little has been known concerning the role of miR‐709 in HCC.Materials and methodsReal‐time RT‐PCR was performed to detect expression of miR‐709 in HCC cell lines and tissues. To further understand its role in HCC, we restored its expression in HepG2 cell line through transfection with miR‐709 mimics or inhibitors. CCK‐8 proliferation assay, migration assay and invasion assay were used to detect functional roles of miR‐709. Luciferase assay and western blotting were performed to detect the target gene of miR‐709.ResultsWe found that miR‐709 was highly expressed in HCC tissues and in HCC cell lines by qRT‐PCR. Re‐expression of miR‐709 in HCC cells remarkably promoted cell migration and invasiveness in vitro. Subsequent investigation revealed that glypican‐5 (GPC5) was a direct and functional target of miR‐709 in HCC cells where overexpression of miR‐709 impaired GPC5‐induced inhibition of proliferation and invasion. Finally, analysis of miR‐709 and GPC5 levels in human HCC tissues revealed that miR‐709 inversely correlated with GPC5 expression.ConclusionsThese results suggest that miR‐709 may positively regulate invasion and metastasis of HCC through targeting GPC5.
The Effect of Habitual Physical Training on Left Ventricular Function During Exercise Assessed by Three‐Dimensional Echocardiography
Authors: Sugiura Kojima Mari , Noda Akiko , Miyata Seiko , Kojima Jun , Hara Yuki , Minoshima Makoto , Murohara Toyoaki 
Published: March 2015

BackgroundStroke volume (SV) in trained athletes continuously increases with progressive exercise intensity. We studied whether physical training affected left ventricle (LV) function response to exercise using 3D echocardiography and tissue Doppler imaging (TDI).MethodsEleven male university athletes and 12 male university nonathletes were enrolled in this study. After baseline data were collected, subjects performed a symptom‐limited supine bicycle ergometer exercise test. Initial workload was 25 Watts (W) and increased 25 W every 3 minutes. At rest and every exercise stage, LV end‐systolic and diastolic volume index (LVEDVI and LVESVI), SV index (SVI), cardiac index (CI), LV ejection fraction (LVEF), and early lateral mitral flow velocity (Ea) were evaluated. Heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) were continuously recorded.ResultsNonathletes showed a slow increase in CI, and SVI reached a plateau value at a HR of 90 beats per minute (bpm). In contrast, CI and SVI increased progressively and continuously in athletes. Both CI and SVI were significantly higher in athletes than in nonathletes at HRs of 100, 110, and 120 bpm. LVEDVI kept increasing in athletes while it plateaued in nonathletes. In contrast, LVESV decreased continuously during exercise in both groups. There was no significant difference in LVEF, Ea, SBP, or DBP at rest and during exercise between the two groups.ConclusionLV responses to exercise in athletes were different from those of in nonathletes; thus, habitual physical training may play an important role in the increase in both SVI and CI in young individuals.
Metabolic characteristics of microbial communities of Aeolian sandy soils induced by saline water drip irrigation in shelter forests
Authors: Jin Z. , Lei J. , Li S. , Xu X. 
Published: March 2015

SummaryThe microbial metabolic activities of soils sampled at eight depths (0–5, 5–15, 15–30, 30–50, 50–70, 70–100, 100–150 and 150–200 cm) in shelter forests (comprising the tree species, Haloxylon sp.) along the Tarim Desert Highway under drip irrigation with different saline waters were investigated by using Biolog technology. Variance analysis and principal component analysis were conducted. The average well colour development (AWCD) values for single carbon source use by microorganisms increased with the incubation time. The microorganisms reached a lag phase within 24 hours of incubation and entered exponential and stationary phases after 48 and 216 hours of incubation, respectively; however, the death phase was not obvious. As the salinity of drip irrigation water increased, the AWCD values significantly decreased; the AWCD value in the land drip‐irrigated with lowest saline water (S8) was roughly 20% larger than that of the land drip‐irrigated with highest saline water (S1), which was mainly caused by the differences in the use of carboxylic acids, amino acids and phenolic compounds by soil microorganisms. The vertical differences in carbon source utilization by soil microbial communities were obvious: these may be caused by the vertical differences in soil organism abundance associated with distribution of roots in the shelter forest. The largest and smallest AWCD values were noted in the 70–100‐cm soil layer and 0–5‐cm topsoil layer, respectively. The correlation coefficients between the AWCD values and soil organic matter, total nitrogen, total phosphorus, total potassium, available potassium, available phosphorus, pH, cation exchange capacity and bulk density were > 0.85. Thus, the differences in carbon source metabolism activities of soil microorganisms were caused mainly by the soil chemical properties, with total nutrients being the main driving factor. Furthermore, the amounts of carboxylic acids, amino acids and polymers provided sensitive markers for distinguishing the ability of soil microorganisms to use carbon sources under drip irrigation with different saline waters. Saline water irrigation affected the soil microbial community in shelter forest and produced obvious differences among the shelter forests irrigated with different saline waters.
Observations on mineral transformations and potential environmental consequences during the oxidation of iron sulphide‐rich materials in incubation experiments
Authors: Shi X. Z. , Oldmeadow D. , Aspandiar M. 
Published: March 2015

SummaryThis paper attempts to acquire a good understanding of the formation and evolution of acid sulphate soils (ASS), as well as to assess the consequent environmental impacts. An incubation experiment to simulate the development of ASS under various weathering scenarios was set up. Fresh monosulphidic black ooze (MBO) material was divided into three parts and each was subjected to different drying and rewetting regimes by controlling an artificial water table in an incubation cell. The observations focused on the changes in mineralogy of the material and reflectance spectral changes during the oxidation process, and the ionic composition and chemical status of the solutions generated. Mineralogical investigations with hyperspectral and XRD analysis showed that frequent inundation produced extensive surface oxidation and a change from iron sulphide minerals to stable end members such as goethite. For the material experiencing moderate or occasional inundation, oxidation was less advanced and a different secondary mineral suite, with iron sulphate minerals such as jarosite, was present. Solutions generated from all the incubation cells were generally acidic with pH around 3.5, indicating that sulphide oxidation occurred rapidly in all cells. Sulphate concentrations in solutions from the different cells were calculated from the measurements of SO42− and other anions in solutions and may approximate the rates of sulphide oxidation. Potential environmental impacts were illustrated in terms of soil acidity, salinity and trace metal release, and the effects of the different wetting/drying regimes on the oxidative process also provided insight into potential weathering effects in a changing climate.
Spatial patterns, storages and sources of black carbon in soils from the catchment of Qinghai Lake, China
Authors: Zhan C. L. , Cao J. J. , Han Y. M. , Wang P. , Huang R. J. , Wei C. , Hu W. G. , Zhang J. Q. 
Published: March 2015

SummaryBlack carbon (BC), composed of char and soot, is an important component of soil organic carbon (SOC), and these materials are potentially important for the global carbon cycle and global climate. A thermal‐optical reflectance method was used to determine the spatial patterns of SOC, BC, char and soot in nine soil types collected from 152 sites in the Qinghai Lake catchment. All of the analytes showed large spatial variability: SOC, BC and char were most abundant in bog soils and least abundant in aeolian soils, while soot concentrations in alpine frost desert and in aeolian soils were about half of those in the other soils. The average BC concentration in the 0–20‐cm soil layers was 1.3 g kg−1, and BC amounted to 5.6% of the SOC. Char, SOC and BC all decreased with soil depth, but soot showed little variation. The proportions of BC to SOC and char to BC showed contrasting trends in four soil profiles; the former increased and the latter decreased with depth. The quantity of SOC sequestered in topsoils of the catchment area was estimated to be 191 Tg; BC accounted for approximately 4.8% of this, and char made up approximately 85% of the total BC stock. The burning of animal dung for domestic cooking apparently was an important source of soil BC: combustion of other biofuels and fossil fuels was the other main source.