bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contractile properties of developing human fetal cardiac muscle
Authors: Racca Alice W. , Klaiman Jordan M. , Pioner J. Manuel , Cheng Yuanhua , Beck Anita E. , Moussavi‐Harami Farid , Bamshad Michael J. , Regnier Michael 
Published: October 2015

Key points
The contractile properties of human fetal cardiac muscle have not been previously studied.
Small‐scale approaches such as isolated myofibril and isolated contractile protein biomechanical assays allow study of activation and relaxation kinetics of human fetal cardiac muscle under well‐controlled conditions.
We have examined the contractile properties of human fetal cardiac myofibrils and myosin across gestational age 59–134 days.
Human fetal cardiac myofibrils have low force and slow kinetics of activation and relaxation that increase during the time period studied, and kinetic changes may result from structural maturation and changes in protein isoform expression.
Understanding the time course of human fetal cardiac muscle structure and contractile maturation can provide a framework to study development of contractile dysfunction with disease and evaluate the maturation state of cultured stem cell‐derived cardiomyocytes.
AbstractLittle is known about the contractile properties of human fetal cardiac muscle during development. Understanding these contractile properties, and how they change throughout development, can provide valuable insight into human heart development, and provide a framework to study the early stages of cardiac diseases that develop in utero. We characterized the contractile properties of isolated human fetal cardiac myofibrils across 8–19 weeks of gestation. Mechanical measurements revealed that in early stages of gestation there is low specific force and slow rates of force development and relaxation, with increases in force and the rates of activation and relaxation as gestation progresses. The duration and slope of the initial, slow phase of relaxation, related to myosin detachment and thin filament deactivation rates, decreased with gestation age. F‐actin sliding on human fetal cardiac myosin‐coated surfaces slowed significantly from 108 to 130 days of gestation. Electron micrographs showed human fetal muscle myofibrils elongate and widen with age, but features such as the M‐line and Z‐band are apparent even as early as day 52. Protein isoform analysis revealed that β‐myosin is predominantly expressed even at the earliest time point studied, but there is a progressive increase in expression of cardiac troponin I (TnI), with a concurrent decrease in slow skeletal TnI. Together, our results suggest that cardiac myofibril force production and kinetics of activation and relaxation change significantly with gestation age and are influenced by the structural maturation of the sarcomere and changes in contractile filament protein isoforms.
High fat diet attenuates glucose‐dependent facilitation of 5‐HT3‐mediated responses in rat gastric vagal afferents
Authors: Troy Amanda E. , Simmonds Sarah S. , Stocker Sean D. , Browning Kirsteen N. 
Published: October 2015

Key points
Glucose regulates the density and function of 5‐HT3 receptors on gastric vagal afferent neurones.
Diet‐induced obesity compromises the excitability and responsiveness of vagal afferents.
In this study, we assessed whether exposure to a high fat diet (HFD) compromises the glucose‐dependent modulation of 5‐HT responses in gastric vagal afferents prior to the development of obesity.
We show that HFD does not alter the response of gastric vagal afferent nerves and neurones to 5‐HT but attenuates the ability of glucose to amplify 5‐HT3‐induced responses.
These results suggest that glucose‐dependent vagal afferent signalling is compromised by relatively short periods of exposure to HFD well in advance of the development of obesity or glycaemic dysregulation.
AbstractGlucose regulates the density and function of 5‐HT3 receptors on gastric vagal afferent neurones. Since diet‐induced obesity attenuates the responsiveness of gastric vagal afferents to several neurohormones, the aim of the present study was to determine whether high fat diet (HFD) compromises the glucose‐dependent modulation of 5‐HT responses in gastric vagal afferents prior to the development of obesity. Rats were fed control or HFD (14% or 60% kilocalories from fat, respectively) for up to 8 weeks. Neurophysiological recordings assessed the ability of 5‐HT to increase anterior gastric vagal afferent nerve (VAN) activity in vivo before and after acute hyperglycaemia, while electrophysiological recordings from gastric‐projecting nodose neurones assessed the ability of glucose to modulate the 5‐HT response in vitro. Immunocytochemical studies determined alterations in the neuronal distribution of 5‐HT3 receptors. 5‐HT and cholecystokinin (CCK) induced dose‐dependent increases in VAN activity in all rats; HFD attenuated the response to CCK, but not 5‐HT. The 5‐HT‐induced response was amplified by acute hyperglycaemia in control, but not HFD, rats. Similarly, although 5‐HT induced an inward current in both control and HFD gastric nodose neurones in vitro, the 5‐HT response and receptor distribution was amplified by acute hyperglycaemia only in control rats. These data suggest that, while HFD does not affect the response of gastric‐projecting vagal afferents to 5‐HT, it attenuates the ability of glucose to amplify 5‐HT effects. This suggests that glucose‐dependent vagal afferent signalling is compromised by short periods of exposure to HFD well in advance of obesity or glycaemic dysregulation.
Cooccurrence of Multiple AmpC β-Lactamases in Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis in Tunisia
Authors: Chérif Thouraya , Saidani Mabrouka , Decré Dominique , Boutiba-Ben Boubaker Ilhem , Arlet Guillaume 
Published: October 2015

ABSTRACT

Over a period of 40 months, plasmid-mediated AmpC β-lactamases were detected in Tunis, Tunisia, in 78 isolates (0.59%) of
Escherichia coli
,
Klebsiella pneumoniae
, and
Proteus mirabilis
. In 67 isolates, only one
ampC
gene was detected, i.e.,
bla
CMY-2-type
(
n
= 33),
bla
ACC
(
n
= 23),
bla
DHA
(
n
= 6) or
bla
EBC
(
n
= 5). Multiple
ampC
genes were detected in 11 isolates, with the following distribution:
bla
MOX-2
,
bla
FOX-3
, and
bla
CMY-4/16
(
n
= 6),
bla
FOX-3
and
bla
MOX-2
(
n
= 3), and
bla
CMY-4
and
bla
MOX-2
(
n
= 2). A great variety of plasmids carrying these genes was found, independently of the species and the
bla
gene. If the genetic context of
bla
CMY-2-type
is variable, that of
bla
MOX-2
, reported in part previously, is unique and that of
bla
FOX-3
is unique and new.
In Vitro
and
In Vivo
Antimicrobial Activities of Minocycline in Combination with Azithromycin, Clarithromycin, or Tigecycline against Pythium insidiosum
Authors: Jesus Francielli P. K. , Loreto Érico S. , Ferreiro Laerte , Alves Sydney H. , Driemeier David , Souza Suyene O. , França Raqueli T. , Lopes Sonia T. A. , Pilotto Maiara B. , Ludwig Aline , Azevedo Maria I. , Ribeiro Tatiana C. , Tondolo Juliana S. M. , Santurio Janio M. 
Published: October 2015

ABSTRACT

The present study investigated the
in vitro
and the
in vivo
interactions among azithromycin, clarithromycin, minocycline, and tigecycline against
Pythium insidiosum
.
In vitro
antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format.
In vivo
efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against
P. insidiosum
were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in
in vitro
synergistic interactions (>60%). Antagonism was not observed. The
in vivo
studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model.
Brucella abortus Invasion of Osteocytes Modulates Connexin 43 and Integrin Expression and Induces Osteoclastogenesis via Receptor Activator of NF-κB Ligand and Tumor Necrosis Factor Alpha Secretion
Authors: Pesce Viglietti Ayelén Ivana , Arriola Benitez Paula Constanza , Gentilini María Virginia , Velásquez Lis Noelia , Fossati Carlos Alberto , Giambartolomei Guillermo Hernán , Delpino María Victoria 
Published: October 2015

ABSTRACTOsteoarticular brucellosis is the most common localization of human active disease. Osteocytes are the most abundant cells of bone. They secrete factors that regulate the differentiation of both osteoblasts and osteoclasts during bone remodeling. The aim of this study is to determine ifBrucella abortusinfection modifies osteocyte function. Our results indicate thatB. abortusinfection induced matrix metalloproteinase 2 (MMP-2), receptor activator for NF-κB ligand (RANKL), proinflammatory cytokines, and keratinocyte chemoattractant (KC) secretion by osteocytes. In addition, supernatants fromB. abortus-infected osteocytes induced bone marrow-derived monocytes (BMM) to undergo osteoclastogenesis. Using neutralizing antibodies against tumor necrosis factor alpha (TNF-α) or osteoprotegerin (OPG), RANKL's decoy receptor, we determined that TNF-α and RANKL are involved in osteoclastogenesis induced by supernatants fromB. abortus-infected osteocytes. Connexin 43 (Cx43) and the integrins E11/gp38, integrin-α, integrin-β, and CD44 are involved in cell-cell interactions necessary for osteocyte survival.B. abortusinfection inhibited the expression of Cx43 but did not modify the expression of integrins. Yet the expression of both Cx43 and integrins was inhibited by supernatants fromB. abortus-infected macrophages.B. abortusinfection was not capable of inducing osteocyte apoptosis. However, supernatants fromB. abortus-infected macrophages induced osteocyte apoptosis in a dose-dependent manner. Taken together, our results indicate thatB. abortusinfection could alter osteocyte function, contributing to bone damage.
A qualitative evidence synthesis on the management of male obesity
Authors: Archibald Daryll , Douglas Flora , Hoddinott Pat , van Teijlingen Edwin , Stewart Fiona , Robertson Clare , Boyers Dwayne , Avenell Alison 
Published: October 2015

ObjectivesTo investigate what weight management interventions work for men, with which men, and under what circumstances.DesignRealist synthesis of qualitative studies.Data sourcesSensitive searches of 11 electronic databases from 1990 to 2012 supplemented by grey literature searches.Study selectionStudies published between 1990 and 2012 reporting qualitative research with obese men, or obese men in contrast to obese women and lifestyle or drug weight management were included. The studies included men aged 16 years or over, with no upper age limit, with a mean or median body mass index of 30 kg/m2in all settings.Results22 studies were identified, including 5 qualitative studies linked to randomised controlled trials of weight maintenance interventions and 8 qualitative studies linked to non-randomised intervention studies, and 9 relevant UK-based qualitative studies not linked to any intervention. Health concerns and the perception that certain programmes had ‘worked’ for other men were the key factors that motivated men to engage with weight management programmes. Barriers to engagement and adherence with programmes included: men not problematising their weight until labelled ‘obese’; a lack of support for new food choices by friends and family, and reluctance to undertake extreme dieting. Retaining some autonomy over what is eaten; flexibility about treats and alcohol, and a focus on physical activity were attractive features of programmes. Group interventions, humour and social support facilitated attendance and adherence. Men were motivated to attend programmes in settings that were convenient, non-threatening and congruent with their masculine identities, but men were seldom involved in programme design.ConclusionsMen's perspectives and preferences within the wider context of family, work and pleasure should be sought when designing weight management services. Qualitative research is needed with men to inform all aspects of intervention design, including the setting, optimal recruitment processes and strategies to minimise attrition.
Geographic location, network patterns and population distribution of rural settlements in Greece
Authors: Asimakopoulos Avraam , Mogios Emmanuel , Xenikos Dimitrios G. 
Published: October 2015

Our work addresses the problem of how social networks are embedded in space, by studying the spread of human population over complex geomorphological terrain. We focus on villages or small cities up to a few thousand inhabitants located in mountainous areas in Greece. This terrain presents a familiar tree-like structure of valleys and land plateaus. Cities are found more often at lower altitudes and exhibit preference on south orientation. Furthermore, the population generally avoids flat land plateaus and river beds, preferring locations slightly uphill, away from the plateau edge. Despite the location diversity regarding geomorphological parameters, we find certain quantitative norms when we examine location and population distributions relative to the (man-made) transportation network. In particular, settlements at radial distance [Formula: see text] away from road network junctions have the same mean altitude, practically independent of [Formula: see text] ranging from a few meters to 10 km. Similarly, the distribution of the settlement population at any given [Formula: see text] is the same for all [Formula: see text]. Finally, the cumulative distribution of the number of rural cities [Formula: see text] is fitted to the Weibull distribution, suggesting that human decisions for creating settlements could be paralleled to mechanisms typically attributed to this particular statistical distribution.
Effect of nano-sized cerium–zirconium oxide solid solution on far-infrared emission properties of tourmaline powders
Authors: Guo Bin , Yang Liqing , Hu Weijie , Li Wenlong , Wang Haojing 
Published: October 2015

Far-infrared functional nanocomposites were prepared by the co-precipitation method using natural tourmaline [Formula: see text], where [Formula: see text] is [Formula: see text], [Formula: see text], [Formula: see text], or vacancy; [Formula: see text] is [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], or [Formula: see text]; [Formula: see text] is [Formula: see text], [Formula: see text], [Formula: see text], or [Formula: see text]; [Formula: see text] is [Formula: see text], [Formula: see text]; and [Formula: see text] is [Formula: see text], [Formula: see text], or [Formula: see text] powders, ammonium cerium(IV) nitrate and zirconium(IV) nitrate pentahydrate as raw materials. The reference sample, tourmaline modified with ammonium cerium(IV) nitrate alone was also prepared by a similar precipitation route. The results of Fourier transform infrared spectroscopy show that tourmaline modified with Ce and Zr has a better far-infrared emission property than tourmaline modified with Ce alone. Through characterization by transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), the mechanism for oxygen evolution during the heat process in the two composite materials was systematically studied. The XPS spectra show that [Formula: see text] ratio inside tourmaline modified with Ce alone can be raised by doping Zr. Moreover, it is showed that there is a higher [Formula: see text] ratio inside the tourmaline modified with Ce and Zr than tourmaline modified with Ce alone. In addition, XRD results indicate the formation of [Formula: see text] and [Formula: see text] crystallites during the heat treatment and further TEM observations show they exist as nanoparticles on the surface of tourmaline powders. Based on these results, we attribute the improved far-infrared emission properties of Ce–Zr doped tourmaline to the enhanced unit cell shrinkage of the tourmaline arisen from much more oxidation of [Formula: see text] to [Formula: see text] inside the tourmaline caused by the change in the catalyst redox properties of [Formula: see text] brought about by doping with [Formula: see text]. In all samples, tourmaline modified with 7.14 wt.% Ce and 1.86 wt.% Zr calcined at 800[Formula: see text]C for 5 h has the best far-infrared emission property with the maximum emissivity value of 98%.
Sorafenib Inhibition of Mcl-1 Accelerates ATRA-Induced Apoptosis in Differentiation-Responsive AML Cells
Authors: Wang Rui , Xia Lijuan , Gabrilove Janice , Waxman Samuel , Jing Yongkui 
Published: October 2015

Abstract
Purpose: All trans-retinoic acid (ATRA) is successful in treating acute promyelocytic leukemia (APL) by inducing terminal differentiation-mediated cell death, but it has limited activity in non-APL acute myeloid leukemia (AML). We aim to improve ATRA therapy of AML by enhancing apoptosis through repression of the antiapoptotic proteins Bcl-2 and Mcl-1.
Experimental Design: APL and AML cell lines, as well as primary AML samples, were used to explore the mechanisms regulating differentiation and apoptosis during ATRA treatment. Stable transfection and gene silencing with siRNA were used to identify the key factors that inhibit apoptosis during induction of differentiation and drugs that accelerate apoptosis.
Results: In differentiation-responsive AML cells, ATRA treatment induces long-lasting repression of Bcl-2 while first upmodulating and then reducing the Mcl-1 level. The Mcl-1 level appears to serve as a gatekeeper between differentiation and apoptosis. During differentiation induction, activation of MEK/ERK and PI3K/Akt pathways by ATRA leads to activation of p90RSK and inactivation of glycogen synthase kinase 3β (GSK3β), which increase Mcl-1 levels by increasing its translation and stability. Sorafenib blocks ATRA-induced Mcl-1 increase by reversing p90RSK activation and GSK3β inactivation, maintains the repressed Bcl-2 level, and enhances ATRA induced apoptosis in non-APL AML cell lines and in primary AML cells.
Conclusions: Inhibition of Mcl-1 is required for apoptosis induction in ATRA differentiation-responsive AML cells. ATRA and sorafenib can be developed as a novel drug combination therapy for AML patients because this drug combination augments apoptosis by inhibiting Bcl-2 and Mcl-1. Clin Cancer Res; 22(5); 1211–21. ©2015 AACR.
Self-reported neck and shoulder pain in adolescents is associated with episodic and chronic migraine
Authors: Landgraf Mirjam N , von Kries Rüdiger , Heinen Florian , Langhagen Thyra , Straube Andreas , Albers Lucia 
Published: October 2015

Aim The aim of this study was to verify the association between self-reported neck/shoulder pain and migraine and to compare findings of chronic and episodic migraine in adolescents. Methods In this cross-sectional study, 601 secondary-school students filled in questionnaires about headache appearance, type and frequency, neck and shoulder pain and lifestyle factors. Results The adjusted strength of the association between reported neck and shoulder pain and migraine (assessed in multinomial regression models) increased with the frequency of migraine: less than once a week (OR = 1.40; 95% CI = (0.85–2.30)), weekly (OR = 2.14; 95% CI = (1.42–3.24)), and at least 15 days/month (OR = 7.27; 95% CI = (3.42–15.44)). Conclusion In adolescents the association between self-reported neck and shoulder pain and migraine is most pronounced in migraine with a high attack frequency.
Leukocyte-Reduced Platelet-Rich Plasma Normalizes Matrix Metabolism in Torn Human Rotator Cuff Tendons
Authors: Cross Jessica A. , Cole Brian J. , Spatny Kaylan P. , Sundman Emily , Romeo Anthony A. , Nicholson Greg P. , Wagner Bettina , Fortier Lisa A. 
Published: October 2015

Background: The optimal platelet-rich plasma (PRP) for treatment of supraspinatus tendinopathy has not been determined. Purpose: To evaluate the effect of low- versus high-leukocyte concentrated PRP products on catabolic and anabolic mediators of matrix metabolism in diseased rotator cuff tendons. Study Design: Controlled laboratory study. Methods: Diseased supraspinatus tendons were treated with PRP made by use of 2 commercial systems: Arthrex Autologous Conditioned Plasma Double Syringe System (Llo PRP) and Biomet GPS III Mini Platelet Concentrate System (Lhi PRP). Tendon explants were placed in 6-well plates and cultured in Llo PRP, Lhi PRP, or control media (Dulbecco’s Modified Eagle Medium + 10% fetal bovine serum) for 96 hours. Tendons were processed for hematoxylin-eosin histologic results and were scored with the modified Bonar scale. Group 1 tendons were defined as moderate tendinopathy (Bonar score <3); group 2 tendons were assessed as severely affected (Bonar score = 3). Transforming growth factor β–1 (TGFβ-1), interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8), and matrix metalloproteinase–9 (MMP-9) concentrations in PRP media were measured by use of enzyme-linked immunosorbent assay after 96 hours of culture with diseased tendon. Tendon messenger RNA expression of collagen type I ( COL1A1), collagen type III ( COL3A1), cartilage oligomeric matrix protein ( COMP), MMP-9, MMP-13, and IL-1β was measured with real-time quantitative polymerase chain reaction. Results: Leukocytes and platelets were significantly more concentrated in Lhi PRP compared with Llo PRP. Increased IL-1β was present in Lhi PRP after culture with group 1 tendons. IL-6 was increased in Lhi PRP after culture with group 2 tendons. Both TGFβ-1 and MMP-9 were increased in Lhi PRP after culture with either tendon group. In Llo PRP cultures, IL-1Ra:IL-1β in PRP used as media and COL1A1:COL3A1 gene expression were increased for group 1 tendon cultures. Gene expression of MMP-9 and IL-1β was increased in group 2 tendons cultured in Llo PRP. There was no significant difference in the expression of MMP-13 or COMP in either group of tendons cultured in Llo PRP or Lhi PRP. Conclusion: Llo PRP promotes normal collagen matrix synthesis and decreases cytokines associated with matrix degradation and inflammation to a greater extent than does Lhi PRP in moderately degenerative tendons. In severely degenerative tendons, neither PRP preparation enhanced matrix synthesis. Clinical Relevance: Llo PRP may promote healing in moderately degenerative rotator cuff tendons.
A theory of expert leadership (TEL) in psychiatry
Authors: Goodall Amanda H 
Published: October 2015

Objective: Leaders’ technical competence – ‘expert knowledge’ – has been shown in many settings to be associated with better organizational performance. In universities, for example, there is longitudinal evidence that research-focused scholars make the best leaders; results from a hospital study show that doctors instead of professional managers are most closely associated with the best performing institutions. To explain these patterns, and raise hypotheses, a theory of expert leadership (TEL) has been developed that might explain these patterns. In this paper the framework for expert leadership is applied to psychiatry. Conclusions: The TEL proposes that psychiatric leaders, as opposed to non-expert managers, improve organizational performance through several channels. First, experts’ knowledge influences organizational strategy. Second, having been ‘one of them’, a psychiatrist understands how to create the optimal work environment for psychiatric teams, through appropriate goal-setting, evaluation and support. These factors are positively associated with workers’ wellbeing and performance. Third, exceptional psychiatrist-leaders are likely to set high standards for hiring. Fourth, leaders’ credibility extends their influence among core workers, and also signals organizational priorities to stakeholders. Finally, a necessary prerequisite of TEL is that expert leaders have direct executive power inclusive of budgetary and strategic oversight.