bluuebunny/crossref_metadata_2025 huggingface dataset:
Biopersistence of silver nanoparticles in tissues from Sprague–Dawley rats
Authors: Lee Ji Hyun , Kim Yong Soon , Song Kyung Seuk , Ryu Hyun Ryol , Sung Jae Hyuck , Park Jung Duck , Park Hyun Min , Song Nam Woong , Shin Beom Soo , Marshak Daniel , Ahn Kangho , Lee Ji Eun , Yu Il Je
Published: August 2013

Silver nanoparticles are known to be distributed in many tissues after oral or inhalation exposure. Thus, understanding the tissue clearance of such distributed nanoparticles is very important to understand the behavior of silver nanoparticles in vivo. For risk assessment purposes, easy clearance indicates a lower overall cumulative toxicity. Accordingly, to investigate the clearance of tissue silver concentrations following oral silver nanoparticle exposure, Sprague–Dawley rats were assigned to 3 groups: control, low dose (100 mg/kg body weight), and high dose (500 mg/kg body weight), and exposed to two different sizes of silver nanoparticles (average diameter 10 and 25 nm) over 28 days. Thereafter, the rats were allowed to recover for 4 months. Regardless of the silver nanoparticle size, the silver content in most tissues gradually decreased during the 4-month recovery period, indicating tissue clearance of the accumulated silver. The exceptions were the silver concentrations in the brain and testes, which did not clear well, even after the 4-month recovery period, indicating an obstruction in transporting the accumulated silver out of these tissues. Therefore, the results showed that the size of the silver nanoparticles did not affect their tissue distribution. Furthermore, biological barriers, such as the blood–brain barrier and blood-testis barrier, seemed to play an important role in the silver clearance from these tissues.
Developing a reporting guideline for social and psychological intervention trials
Authors: Mayo-Wilson Evan , Grant Sean , Hopewell Sally , Macdonald Geraldine , Moher David , Montgomery Paul
Published: August 2013

Social and psychological interventions are often complex. Understanding randomised controlled trials (RCTs) of these complex interventions requires a detailed description of the interventions tested and the methods used to evaluate them; however, RCT reports often omit, or inadequately report, this information. Incomplete and inaccurate reporting hinders the optimal use of research, wastes resources, and fails to meet ethical obligations to research participants and consumers. In this paper, we explain how reporting guidelines have improved the quality of reports in medicine, and describe the ongoing development of a new reporting guideline for RCTs: CONSORT-SPI (an Extension for social and psychological interventions). We invite readers to participate in the project by visiting our website, in order to help us reach the best-informed consensus on these guidelines (http://tinyurl.com/CONSORT-study).
A randomized controlled dismantling trial of post-workshop consultation strategies to increase effectiveness and fidelity to an evidence-based psychotherapy for Posttraumatic stress disorder
Authors: Wiltsey Stirman Shannon , Shields Norman , Deloriea Josh , Landy Meredith SH , Belus Jennifer M , Maslej Marta M , Monson Candice M
Published: August 2013

Background

Posttraumatic Stress Disorder (PTSD) is a serious mental health condition with substantial costs to individuals and society. Among military veterans, the lifetime prevalence of PTSD has been estimated to be as high as 20%. Numerous research studies have demonstrated that short-term cognitive-behavioral psychotherapies, such as Cognitive Processing Therapy (CPT), lead to substantial and sustained improvements in PTSD symptoms. Despite known benefits, only a minority of clinicians provide these therapies. Transferring this research knowledge into clinical settings remains one of the largest hurdles to improving the health of veterans with PTSD. Attending a workshop alone is insufficient to promote adequate knowledge transfer and sustained skill; however, relatively little research has been conducted to identify effective post-training support strategies.

Methods

The current study investigates whether clinicians receiving post-workshop support (six-month duration) will deliver CPT with greater fidelity (i.e., psychotherapy adherence and competence) and have improved patient outcomes compared with clinicians receiving no formal post-workshop support. The study conditions are: technology-enhanced group tele-consultation; standard group tele-consultation; and fidelity assessment with no consultation. The primary outcome is independent assessment (via audio-recordings) of the clinicians’ adherence and competence in delivering CPT. The secondary outcome is observed changes in patient symptoms during and following treatment as a function of clinician fidelity. Post-consultation interviews with clinicians will help identify facilitators and barriers to psychotherapy skill acquisition. The study results will inform how best to implement and transfer evidence-based psychotherapy (e.g., CPT) to clinical settings to attain comparable outcomes to those observed in research settings.

Discussion

Findings will deepen our understanding of how much and what type of support is needed following a workshop to help clinicians become proficient in delivering a new protocol. Several influences on clinician learning and patient outcomes will be discussed. An evidence-based model of clinical consultation will be developed, with the ultimate goal of informing policy and influencing best practice in clinical consultation.

Trial registration

ClinicalTrials.gov:NCT01861769
Electrons for intraoperative radiotherapy in selected breast-cancer patients: late results of the Montpellier phase II trial
Authors: Lemanski Claire , Azria David , Gourgou-Bourgade Sophie , Ailleres Norbert , Pastant Aurelie , Rouanet Philippe , Fenoglietto Pascal , Dubois Jean-Bernard , Gutowski Marian
Published: August 2013

Background

The Montpellier cancer institute phase II trial started in 2004 and evaluated the feasibility of intraoperative radiotherapy (IORT) technique given as a sole radiation treatment for patients with an excellent prognostic and very low recurrence risk.

Methods

Forty-two patients were included between 2004 and 2007. Inclusion criteria were patients ≥ 65 years old, T0-T1, N0, ductal invasive unifocal carcinoma, free-margin > 2 mm. IORT was delivered using dedicated linear accelerator. One fraction of 21 Gy was prescribed and specified at the 90% isodose using electrons. In vivo dosimetry was performed for all patients. Primary end-point was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, specific and overall survival.

Results

At inclusion, median age was 72 years (range, 66–80). Median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Late cosmetic results were good at 5 years despite the poor agreement of accuracy assessment between patients and physicians. Four patients (9.5%) experienced a local failure and underwent salvage mastectomy. The 5 year-disease free survival is 92.7% (range 79.1−97.6). All patients are still alive with a median follow-up of 72 months (range 66–74).

Conclusion

Our results confirm with a long-term follow-up that exclusive partial breast IORT is feasible for early-breast cancer in selected patients. IORT provides good late cosmetics results and should be considered as a safe and very comfortable “one-step” treatment procedure. Nevertheless, patient assessments are essential for long-term quality results.
Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map
Authors: Hiramatsu Ryo , Kawabata Shinji , Furuse Motomasa , Miyatake Shin-Ichi , Kuroiwa Toshihiko
Published: August 2013

Background

Radiologic response of brain tumors is traditionally assessed according to the Macdonald criteria 10 weeks from the start of therapy. Because glioblastoma (GB) responds in days rather than weeks after boron neutron capture therapy (BNCT) that is a form of tumor-selective particle radiation, it is inconvenient to use the Macdonald criteria to assess the therapeutic efficacy of BNCT by gadolinium-magnetic resonance imaging (Gd-MRI). Our study assessed the utility of functional diffusion map (fDM) for evaluating response patterns in GB treated by BNCT.

Methods

The fDM is an image assessment using time-dependent changes of apparent diffusion coefficient (ADC) in tumors on a voxel-by-voxel approach. Other than time-dependent changes of ADC, fDM can automatically assess minimum/maximum ADC, Response Evaluation Criteria In Solid Tumors (RECIST), and the volume of enhanced lesions on Gd-MRI over time. We assessed 17 GB patients treated by BNCT using fDM. Additionally, in order to verify our results, we performed a histopathological examination using F98 rat glioma models.

Results

Only the volume of tumor with decreased ADC by fDM at 2 days after BNCT was a good predictor for GB patients treated by BNCT (P value = 0.022 by log-rank test and 0.033 by wilcoxon test). In a histopathological examination, brain sections of F98 rat glioma models treated by BNCT showed cell swelling of both the nuclei and the cytoplasm compared with untreated rat glioma models.

Conclusions

The fDM could identify response patterns in BNCT-treated GB earlier than a standard radiographic assessment. Early detection of treatment failure can allow a change or supplementation before tumor progression and might lead to an improvement of GB patients’ prognosis.
Pure 16q21q22.1 deletion in a complex rearrangement possibly caused by a chromothripsis event
Authors: Genesio Rita , Ronga Valentina , Castelluccio Pia , Fioretti Gennaro , Mormile Angela , Leone Graziella , Conti Anna , Cavaliere Maria Luigia , Nitsch Lucio
Published: August 2013

Background

Partial monosomies of chromosome 16q are rare and overlapping effects from complex chromosomal rearrangements often hamper genotype-phenotype correlations for such imbalances. Here, we report the clinical features of an isolated partial monosomy 16q21q22.1 in a boy with a complex de novo rearrangement possibly resulting from a chromothripsis event.

Results

The patient presented with low birth weight, microcephaly, developmental delay, facial dysmorphisms, short stature, dysmorphic ears and cardiopathy. Standard and molecular cytogenetics showed a complex rearrangement characterised by a pericentromeric inversion in one of chromosomes 12 and an inverted insertional translocation of the 12q14q21.1 region, from the rearranged chromosome 12, into the q21q22.1 tract of a chromosome 16. Array-CGH analysis unravelled a partial 16q21q22.1 monosomy, localised in the rearranged chromosome 16.

Conclusions

The comparison of the present case to other 16q21q22 monosomies contributed to narrow down the critical region for cardiac anomalies in the 16q22 deletion syndrome. However, more cases, well characterised both for phenotypic signs and genomic details, are needed to further restrict candidate regions for phenotypic signs in 16q deletions. The present case also provided evidence that a very complex rearrangement, possibly caused by a chromothripsis event, might be hidden behind a classical phenotype that is specific for a syndrome.
A novel angiomatoid epithelioid sarcoma cell line, Asra-EPS, forming tumors with large cysts containing hemorrhagic fluid in vivo
Authors: Imura Yoshinori , Naka Norifumi , Outani Hidetatsu , Yasui Hirohiko , Takenaka Satoshi , Hamada Ken-ichiro , Ozaki Ritsuro , Kaya Mitsunori , Yoshida Ken-ichi , Morii Eiichi , Myoui Akira , Yoshikawa Hideki
Published: August 2013

Background

Whereas we can use several human epithelioid sarcoma (ES) cell lines for basic and preclinical research, an angiomatoid ES cell line has not been reported to date. We have treated a case of an angiomatoid ES developing in the right upper extremity of a 67-year-old man.

Methods

An angiomatoid ES cell line, Asra-EPS was newly established and characterized for its morphology, growth rate and chromosomal analysis. Tumorigenicity of Asra-EPS cells was also analyzed in athymic nude mice.

Results

Asra-EPS cells were round, polygonal or spindle-shaped with an abundant cytoplasm and have been maintained continuouslyin vitrofor over 150 passages during more than 15 months. These cells secreted cancer antigen 125 (CA 125), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) into the culture medium. Asra-EPS cells were tumorigenic when implanted in nude mice with tumors reaching a volume of 1000 mm3at around 50 days. Histological features of tumors formed in mice were essentially the same as those of the original tumor, exhibiting a multinodular proliferation of eosinophilic epithelioid and spindle-shaped cells with prominent areas of hemorrhage and blood-filled cystic spaces strikingly corresponding to the potential of hemorrhagic cyst formation in the original tumor. They showed immunopositive staining for cytokeratins (AE1/AE3 and CAM5.2), epithelial membrane antigen (EMA), vimentin, CD31, CD34 and CA 125, but negative for integrase interactor 1 (INI-1) and factor VIII-related antigen.

Conclusions

The established cell line represents a biologically relevant new tool to investigate the molecular pathology of human angiomatoid ES and to evaluate the efficacy of novel therapeutics bothin vitroandin vivo.
Development of children's hymenoptera venom allergy quality of life scale (CHVAQoLS)
Authors: Cichocka‐Jarosz Ewa , Brzyski Piotr , Tobiasz‐Adamczyk Beata , Lis Grzegorz , Pietrzyk Jacek J
Published: August 2013

Background

Venom allergy is a rare but life‐threatening disease and may have a considerable impact on the health‐related quality of life (HRQoL) of patients, especially children. This paper presents development of the HRQoL scale for children and adolescents with Hymenoptera venom allergy (HVA).

Methods

The study sample consisted of 71 children, born between 1992 and 2000, who presented with a history of insect sting reaction when referred for consultation in the allergy center of Polish‐American Children's Hospital, Krakow, Poland, during the period from 2000 to 2010. The initial pool of 60 items ‐ divided into 6 domains ‐ was prepared. The items with intercorrelations higher than 0.7 were removed from each domain and then principal component analysis was conducted for each domain separately, to provide a one‐dimensional subscale for each domain. Reliability of the subscales was assessed using Cronbach alpha coefficient in terms of Classical Test Theory and with rho coefficient in terms of Item Response Theory. The multidimensionality of the scale was tested using multi‐trait scaling.

Results

Three to four items from each domain were subsequently selected to constitute six subscales. Rho coefficients for all the subscales reached 0.8, similar results were achieved with the Cronbach alpha coefficients. Multi‐trait method showed that the majority of the items indicated stronger correlations with their own subscales than with other subscales, which proves that our constructed subscales measure different dimensions of HRQoL.

Conclusions

The presented scale comprises high validity and reliability subscales measuring six dimensions of HRQoL related to Hymenoptera venom allergy in children and adolescents. Such information may be useful in everyday clinical practice.
Molecular basis of HHQ biosynthesis: molecular dynamics simulations, enzyme kinetic and surface plasmon resonance studies
Authors: Steinbach Anke , Maurer Christine K , Weidel Elisabeth , Henn Claudia , Brengel Christian , Hartmann Rolf W , Negri Matthias
Published: August 2013

Background

PQS (Pseudomonas Quinolone Signal) and its precursor HHQ are signal molecules of the P. aeruginosa quorum sensing system. They explicate their role in mammalian pathogenicity by binding to the receptor PqsR that induces virulence factor production and biofilm formation. The enzyme PqsD catalyses the biosynthesis of HHQ.

Results

Enzyme kinetic analysis and surface plasmon resonance (SPR) biosensor experiments were used to determine mechanism and substrate order of the biosynthesis. Comparative analysis led to the identification of domains involved in functionality of PqsD. A kinetic cycle was set up and molecular dynamics (MD) simulations were used to study the molecular bases of the kinetics of PqsD. Trajectory analysis, pocket volume measurements, binding energy estimations and decompositions ensured insights into the binding mode of the substrates anthraniloyl-CoA and β-ketodecanoic acid.

Conclusions

Enzyme kinetics and SPR experiments hint at a ping-pong mechanism for PqsD with ACoA as first substrate. Trajectory analysis of different PqsD complexes evidenced ligand-dependent induced-fit motions affecting the modified ACoA funnel access to the exposure of a secondary channel. A tunnel-network is formed in which Ser317 plays an important role by binding to both substrates. Mutagenesis experiments resulting in the inactive S317F mutant confirmed the importance of this residue. Two binding modes for β-ketodecanoic acid were identified with distinct catalytic mechanism preferences.
Role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in denervation-induced atrophy in aged muscle: facts and hypotheses
Authors: Gouspillou Gilles , Picard Martin , Godin Richard , Burelle Yan , Hepple Russell T
Published: August 2013

Aging-related loss of muscle mass, a biological process named sarcopenia, contributes to mobility impairment, falls, and physical frailty, resulting in an impaired quality of life in older people. In view of the aging of our society, understanding the underlying mechanisms of sarcopenia is a major health-care imperative. Evidence obtained from human and rodent studies demonstrates that skeletal muscle denervation/reinnervation cycles occur with aging, and that progressive failure of myofiber reinnervation is a major cause of the accelerating phase of sarcopenia in advanced age. However, the mechanisms responsible for the loss of myofiber innervation with aging remain unknown. The two major strategies that counteract sarcopenia, that is, caloric restriction and endurance training, are well known to protect neuromuscular junction (NMJ) integrity, albeit through undefined mechanisms. Interestingly, both of these interventions better preserve PGC-1α expression with aging, a transcriptional coactivator which has recently been shown to regulate key proteins involved in maintaining NMJ integrity. We therefore propose that the aging-related decline in PGC-1α may be a central mechanism promoting instability of the NMJ and consequently, aging-related alterations of myofiber innervation in sarcopenia. Similarly, the promotion of PGC-1α expression by both caloric restriction and exercise training may be fundamental to their protective benefits for aging muscle by better preserving NMJ integrity.
Participation and performance trends in ‘Ultraman Hawaii’ from 1983 to 2012
Authors: Meili Dimirela , Knechtle Beat , Rüst Christoph Alexander , Rosemann Thomas , Lepers Romuald
Published: August 2013

Background

Participation and performance trends have been investigated in a single stage Ironman triathlon such as the ‘Ironman Hawaii,’ but not for a multi-stage ultra-triathlon such as the ‘Ultraman Hawaii’ covering a total distance of 515 km. The aims of this study were to analyze (1) changes in participation and performance, (2) sex-related differences in overall and split time performances, and (3) the age of peak performance in Ultraman Hawaii.

Methods

Age and race times including split times for 98 women and 570 men who successfully finished Ultraman Hawaii (day 1 with 10-km swimming and 145-km cycling, day 2 with 276-km cycling, and day 3 with 84-km running) between 1983 and 2012 were analyzed. Changes in variables over time of annual winners and annual top three women and men were investigated using simple linear regression analyses.

Results

The number of female finishers increased (r
2 = 0.26, p < 0.01), while the number of male finishers remained stable (r
2 = 0.03, p > 0.05). Overall race times decreased for both female (r
2 = 0.28, p < 0.01) and male (r2 = 0.14, p < 0.05) winners and for both the annual top three women (r
2 = 0.36, p < 0.01) and men (r2 = 0.14, p = 0.02). The sex difference in performance decreased over time from 24.3% to 11.5% (r
2 = 0.39, p < 0.01). For the split disciplines, the time performance in cycling on day 1 (r
2 = 0.20, p < 0.01) and day 2 decreased significantly for men (r
2 = 0.41, p < 0.01) but for women only on day 2 (r
2 = 0.45, p < 0.01). Split times showed no changes in swimming and running. The age of the annual winners increased from 28 to 47 years for men (r
2 = 0.35, p < 0.01) while it remained stable at 32 ± 6 years for women (r
2 < 0.01, p > 0.05). The age of the annual top three finishers increased from 33 ± 6 years to 48 ± 3 years for men (p < 0.01) and from 29 ± 7 years to 49 ± 2 years for women (p < 0.01).

Conclusions

Both the annual top three women and men improved performance in Ultraman Hawaii during the 1983–2012 period although the age of the annual top three women and men increased. The sex-related difference in performance decreased over time to reach approximately 12% similar to the reports of other endurance and ultra-endurance events. Further investigations are required to better understand the limiting factors of the multi-activities ultra-endurance events taking place over several days.
The effects of international migration on the well-being of native populations in Europe
Authors: Betz William , Simpson Nicole B
Published: August 2013

Very little is understood about how immigrants affect the happiness, or subjective well-being of natives. We use the European Social Survey to analyze the effects of aggregate immigration flows on the subjective well-being of native-born populations in a panel of 26 countries between 2002 and 2010. We find that recent immigrant flows have a nonlinear, yet overall positive impact on the well-being of natives, with the largest effects coming from immigrant flows arriving in the previous year. Our results are small in magnitude and in practical application; only large immigrant flows would affect native well-being significantly.

JEL codes

F22, I31, O15
Predicting mandibular growth increment on the basis of cervical vertebral dimensions in Iranian girls
Authors: Moshfeghi Mahkameh , Rahimi Hajir , Rahimi Hoda , Nouri Mahtab , Bagheban Alireza Akbarzadeh
Published: August 2013

Background

The purpose of this longitudinal study was to establish an equation to predict incremental mandibular length on the basis of the analysis of the cervical vertebrae on a single cephalometric radiograph and to compare the predictive accuracy with the method by Mito et al.

Methods

Data consist of a group of 33 Iranian girls, 9 to 11 years old with two lateral cephalometric radiographs taken at a 24-month interval. For each individual, on the lateral cephalometric radiographs, points and lines for the description of the morphologic characteristics of the third and fourth cervical vertebral bodies were traced and measured. The real mandibular length increment (MLI) in this period was determined by the difference between the second (24 months) and first (baseline) radiographs: MLI = Ar-Pog (second) − Ar-Pog (first). An equation was determined to calculate mandibular length increments on the basis of the measurements in the third and fourth cervical vertebral bodies. The predictive accuracy was assessed using multiple regression analysis.

Results

The adjusted R
2 for this equation was 54.9% which is a reliable value for evaluating prediction accuracy .The average error between the predicted increment and the actual increment was 0.149 mm for our method and 5.87 mm for the method by Mito et al.

Discussion

There are two items that contributed to easier and better prediction accuracy in our equation: (1) higher R
2 and (2) fewer independent variables. In our subjects, the prediction accuracy was lower when using Mito et al.'s method, which could be due to genetic and environmental factors and selected age range.

Conclusion

These results indicate that cervical vertebral measurements, obtained in lateral cephalograms, are able to predict properly the mandibular growth potential.
Frictional resistance in monocrystalline ceramic brackets with conventional and nonconventional elastomeric ligatures
Authors: Galvão Mariana Bulhoes , Camporesi Matteo , Tortamano André , Dominguez Gladys Cristina , Defraia Efisio
Published: August 2013

Background

The objective of this study was to compare the frictional forces generated by three types of monocrystalline ceramic brackets coupled with conventional elastomeric ligatures (CEL) and nonconventional elastomeric ligatures (NCEL) during the alignment of apically displaced teeth at the maxillary arch.

Methods

All tests (a total of 480 tests) were carried out in a dry state on a universal testing machine with a testing model consisting of three 0.022-in. monocrystalline ceramic preadjusted brackets (from the maxillary right second premolar through the right central incisor). The canine bracket was bonded to a sliding bar that allowed for different vertical positions. The frictional forces generated by a 0.012- and 0.014-in. superelastic nickel titanium wire (SENT) with conventional and nonconventional ligatures at various amounts of canine misalignment (1.5, 3.0, 4.5, and 6.0 mm) were recorded. Comparisons between the different types of bracket-wire-ligature systems were carried out by means of analysis of variance on ranks with Tukey's post hoc test (P < 0.05).

Results

No significant differences were assessed among the three types of monocrystalline brackets with NCEL when coupled with 0.012-in. SENT. Radiance brackets with NCEL coupled with 0.014-in. SENT showed significantly greater frictional force than Inspire Ice brackets and Pure brackets with NCEL. A significantly greater amount of frictional force was generated with CEL when compared with NCEL for all the tested variables, with the exception of the Pure brackets with 0.012-in. SENT at 1.5 and 3.0 mm of canine misalignment where similar frictional forces were found.

Conclusions

Nonconventional elastomeric ligatures are able to reduce friction in monocrystalline ceramic brackets.
Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage
Authors: Van Pham Phuc , Bui Khanh Hong-Thien , Ngo Dat Quoc , Vu Ngoc Bich , Truong Nhung Hai , Phan Nhan Lu-Chinh , Le Dung Minh , Duong Triet Dinh , Nguyen Thanh Duc , Le Vien Tuong , Phan Ngoc Kim
Published: August 2013

Introduction

Adipose-derived stem cells (ADSCs) have been isolated, expanded, and applied in the treatment of many diseases. ADSCs have also been used to treat injured articular cartilage. However, there is controversy regarding the treatment efficiency. We considered that ADSC transplantation with activated platelet-rich plasma (PRP) may improve injured articular cartilage compared with that of ADSC transplantation alone. In this study, we determined the role of PRP in ADSC transplantation to improve the treatment efficiency.

Methods

ADSCs were isolated and expanded from human adipose tissue. PRP was collected and activated from human peripheral blood. The effects of PRP were evaluated in vitro and in ADSC transplantation in vivo. In vitro, the effects of PRP on ADSC proliferation, differentiation into chondrogenic cells, and inhibition of angiogenic factors were investigated at three concentrations of PRP (10%, 15% and 20%). In vivo, ADSCs pretreated with or without PRP were transplanted into murine models of injured articular cartilage.

Results

PRP promoted ADSC proliferation and differentiation into chondrogenic cells that strongly expressed collagen II, Sox9 and aggrecan. Moreover, PRP inhibited expression of the angiogenic factor vascular endothelial growth factor. As a result, PRP-pretreated ADSCs improved healing of injured articular cartilage in murine models compared with that of untreated ADSCs.

Conclusion

Pretreatment of ADSCs with PRP is a simple method to efficiently apply ADSCs in cartilage regeneration. This study provides an important step toward the use of autologous ADSCs in the treatment of injured articular cartilage.
Sphingosine-1-phosphate can promote mast cell hyper-reactivity through regulation of contactin-4 expression
Authors: Olivera Ana , Kitamura Yoshiaki , Wright Laurel D , Allende Maria L , Chen Weiping , Kaneko-Goto Tomomi , Yoshihara Yoshihiro , Proia Richard L , Rivera Juan
Published: August 2013

Both genes and the environment are determinants in the susceptibility to allergies and may alter the severity of the disease. We explored whether an increase in the levels of the lipid mediator S1P in vivo, a condition found during allergic asthma, could affect the sensitivity or the response of MCs to IgE/Ag and the onset of allergic disease. We found that increasing S1P levels by genetic deletion of S1P lyase, the enzyme catabolizing S1P, led to elevated activity of circulating tryptase. Accordingly, MCs of S1P lyase-deficient mice were mostly degranulated in the tissues and showed enhanced calcium levels, degranulation, and cytokine production in response to IgE/Ag in vitro. Th 1-skewed mice (C57BL/6) had lower levels of S1P in circulation and histamine responses than did Th 2-skewed (129/Sv) mice. However, when S1P levels were increased by pharmacologic inhibition of S1P lyase, the C57BL/6 mice showed increased histamine release into the circulation and anaphylactic responses similar to those in the 129/Sv mice. Culturing of MCs in the presence of S1P enhanced their degranulation responses, and when the S1P-treated MCs were used to reconstitute MC-deficient (KitW-sh) mice, they caused enhanced anaphylaxis. Gene expression arrays in S1P lyase-deficient MCs and MCs treated with S1P continuously revealed increased expression of numerous genes, including the adhesion molecule CNTN4,which contributed to the enhanced responses. Our findings argue that dysregulation in the metabolism of S1P is a contributing factor in modulating MC responsiveness and the allergic response.
Editorial: Of Mice and Men—Yet Again
Authors: Rosen Henry
Published: August 2013

Discussion of distinct features between human and murine innate immune systems.
Using spatial derivatives of electromagnetic data to map lateral conductance variations in thin-sheet models: Applications over mine tailings ponds
Authors: Kolaj Michal , Smith Richard
Published: August 2013

Mine waste, variable overburden, and the saprolite associated with nickel laterites have conductivity thicknesses (conductances) that vary laterally. In order for electromagnetic methods to be used to easily map lateral changes in conductance over thin-sheet-like bodies such as these, a simple conductance estimation method has been developed from Price’s equation. Through forward modeling, we found that assuming a uniform conductance and solving for an apparent conductance was sensitive enough to identify lateral conductance changes. The method was independent of the transmitter location, and each measurement provided a direct estimate of the apparent conductance below that station. The receiver can be moved around quickly allowing for lateral variations in apparent conductance to be determined efficiently. However, one of the required terms in the equation used is the vertical derivative of the secondary vertical magnetic field ([Formula: see text]). The accurate measurement of spatial electromagnetic derivatives requires a good signal-to-noise ratio (S/N), which can be hampered by low derivative signal values. Field studies performed over a dry tailings pond in Sudbury, Ontario, Canada, showed that an S/N greater than three was achievable even with [Formula: see text] values of less than [Formula: see text]. Apparent conductance estimates revealed that the tailings had a large resistive zone associated with surface vegetation, which may be correlated with favorable growing conditions and/or less conductive or thinner tailing material. Larger apparent conductances in other areas may be related to zones of thicker tailings and/or more conductive material (possibly due to increased metal content). Further drilling and sampling work is required to answer these ambiguities. Regardless, mapping the conductance of a thin sheet is an important step toward assessing if there are leftover metals in mine waste. However, the developed method is general and can be used in many other situations involving laterally varying thin bodies.
On the relationship between induced polarization and surface conductivity: Implications for petrophysical interpretation of electrical measurements
Authors: Weller Andreas , Slater Lee , Nordsiek Sven
Published: August 2013

Petrophysical interpretation of resistivity measurements is often hindered by the dependence of resistivity on the interconnected pore fluids and the interconnected pore surfaces. Induced polarization (IP) measurements yield parameters that are only controlled by the interconnected pore surfaces, thereby offering the opportunity to constrain interpretation of resistivity measurements. Using a database composed of 63 sandstone and unconsolidated sediment samples covering nine independent investigations, we identified a strong linear relationship between the real part of surface conductivity ([Formula: see text]) determined from multisalinity ([Formula: see text]) resistivity measurements and the imaginary conductivity ([Formula: see text]) measured with IP at a frequency of about 1 Hz. We found [Formula: see text] with a coefficient of determination ([Formula: see text]) of 0.911 and a standard deviation of [Formula: see text] of 0.022. We found a similar relation when the normalized chargeability (from Debye decomposition) of the frequency dependence of the IP response is used instead of [Formula: see text]. By estimating the true formation factor ([Formula: see text]) recorded at high salinity, we solved for [Formula: see text] and found that it parallels the salinity dependency of the imaginary conductivity, [Formula: see text], as reported in recent studies. We also found that the value of the [Formula: see text] determined from this experimental study was generally consistent with predictions of the POLARIS model when the mobility of the ions in the Stern layer was assumed to be [Formula: see text] of the mobility of the ions in the diffuse layer (considered equal to the mobility of the ions in the bulk solution). We discovered how the identified relationship can be used to significantly improve (1) the estimation of the true formation factor and (2) the groundwater conductivity, from a single salinity resistivity measurement when an IP measurement is also made. The approach offers an opportunity to improve estimation of porosity, formation factor, and salinity in well logging and hydrogeophysical investigations.
Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: individual patient data meta-analysis
Authors: Meijer A. , Conradi H. J. , Bos E. H. , Anselmino M. , Carney R. M. , Denollet J. , Doyle F. , Freedland K. E. , Grace S. L. , Hosseini S. H. , Lane D. A. , Pilote L. , Parakh K. , Rafanelli C. , Sato H. , Steeds R. P. , Welin C. , de Jonge P.
Published: August 2013

Background

The association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity.

Aims

To combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity.

Method

An individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses.

Results

Sixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26–1.38,P<0.001) for all-cause mortality and 1.19 (95% CI 1.14–1.24,P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively.

Conclusions

The association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depressionz-score.
Encode and a new landscape for psychiatric genetics
Authors: Nair Akshay , Howard Robert
Published: August 2013

Despite rigorous research into the genetics of neuropsychiatric disorders, the mechanism by which polygenic risk leads to complex clinical phenotypes remains unclear. The Encyclopedia of DNA Elements (ENCODE) project gives us new insight into gene regulation, and gene–gene and gene–environment interaction.

Better understanding of these key genomic mechanisms may provide the answers we have been searching for.
Joint assessment out of hours: assessing the benefits for patients and junior doctors
Authors: Boyd Laura , Crawford Colin , Wong Eugene
Published: August 2013

Aims and method

We examined the impact of implementing a new Acute Mental Health Emergency Assessment Protocol (AMHEAP) on joint psychiatric assessments out of hours within Forth Valley, Scotland, over the course of 4 calendar months. The protocol states that assessments should be carried out by a junior doctor and a registered, qualified mental health nurse. The impact measures were taken as admission rates and experience of the doctor in training.

Results

In the 4 months that were examined (1 June–30 September 2011), 79.5% of out-of-hours emergency assessments were performed jointly. Admission rates were significantly decreased (P<0.001) compared with a similar period in 2008, before the AMHEAP protocol was developed. Most junior doctors valued the experience of joint assessment.

Clinical implications

Joint assessment can enhance patient experience, reduce hospital admission, and provide a learning opportunity for junior doctors in emergency psychiatric assessments. However, it represents a move away from the doctor as sole decision maker.
Stigma of mental illness and help-seeking intention in university students
Authors: Lally John , ó Conghaile Aengus , Quigley Sara , Bainbridge Emma , McDonald Colm
Published: August 2013

Aims and method

A cross-sectional study to ascertain levels of personal and perceived public mental illness stigma in a university student population and the association between the respective levels of stigma and help-seeking intention. An adaptation of the Discrimination-Devaluation scale was used.

Results

A total of 735 students participated in the study (response rate 77%). There were higher mean perceived public stigma levels than personal stigma levels. Perceived public stigma was not significantly associated with future non-help-seeking intention (odds ratio (OR) = 0.871, P = 0.428). Personal stigma was significantly associated with a decreased likelihood of future help-seeking intention (OR = 1.44, P = 0.043). Being younger than 25, having no history of or treatment for mental illness and having no personal contact with someone with a history of mental illness were all associated with higher personal stigma levels.

Clinical implications

This study indicates that personal stigma as distinct from perceived public stigma is a significant barrier to mental health utilisation for a student population and future stigma reduction campaigns could strategically focus on this.
Drug policy reform – the opportunity presented by ‘legal highs'
Authors: Meacher Baroness Molly C.
Published: August 2013

Current UK policy on drugs does little to reduce the potential harms to young people using drugs and in some ways can exacerbate them. The dramatic increase in the number of new psychoactive substances available in the UK carries the risk of increasing those harms and demands a new approach to drug regulation. The All-Party Parliamentary Group for Drug Policy Reform calls for an independent drugs classification body, the introduction of a new category for psychoactive substances whereby their supply can be regulated and a review of the government lead for drugs to ensure a health focus. The Group's proposal and supporting evidence are set out in full.
Predetermined embryonic glial cells form the distinct glial sheaths of theDrosophilaperipheral nervous system
Authors: von Hilchen Christian M. , Bustos Álvaro E. , Giangrande Angela , Technau Gerhard M. , Altenhein Benjamin
Published: August 2013

One of the numerous functions of glial cells in Drosophila is the ensheathment of neurons to isolate them from the potassium-rich haemolymph, thereby establishing the blood-brain barrier. Peripheral nerves of flies are surrounded by three distinct glial cell types. Although all embryonic peripheral glia (ePG) have been identified on a single-cell level, their contribution to the three glial sheaths is not known. We used the Flybow system to label and identify each individual ePG in the living embryo and followed them into third instar larva. We demonstrate that all ePG persist until the end of larval development and some even to adulthood. We uncover the origin of all three glial sheaths and describe the larval differentiation of each peripheral glial cell in detail. Interestingly, just one ePG (ePG2) exhibits mitotic activity during larval stages, giving rise to up to 30 glial cells along a single peripheral nerve tract forming the outermost perineurial layer. The unique mitotic ability of ePG2 and the layer affiliation of additional cells were confirmed by in vivo ablation experiments and layer-specific block of cell cycle progression. The number of cells generated by this glial progenitor and hence the control of perineurial hyperplasia correlate with the length of the abdominal nerves. By contrast, the wrapping and subperineurial glia layers show enormous hypertrophy in response to larval growth. This characterisation of the embryonic origin and development of each glial sheath will facilitate functional studies, as they can now be addressed distinctively and genetically manipulated in the embryo.
Histone variant H3.3 maintains a decondensed chromatin state essential for mouse preimplantation development
Authors: Lin Chih-Jen , Conti Marco , Ramalho-Santos Miguel
Published: August 2013

Histone variants can replace canonical histones in the nucleosome and modify chromatin structure and gene expression. The histone variant H3.3 preferentially associates with active chromatin and has been implicated in the regulation of a diverse range of developmental processes. However, the mechanisms by which H3.3 may regulate gene activity are unclear and gene duplication has hampered an analysis of H3.3 function in mouse. Here, we report that the specific knockdown of H3.3 in fertilized mouse zygotes leads to developmental arrest at the morula stage. This phenotype can be rescued by exogenous H3.3 but not by canonical H3.1 mRNA. Loss of H3.3 leads to over-condensation and mis-segregation of chromosomes as early as the two-cell stage, with corresponding high levels of aneuploidy, but does not appear to affect zygotic gene activation at the two-cell stage or lineage gene transcription at the morula stage. H3.3-deficient embryos have significantly reduced levels of markers of open chromatin, such as H3K36me2 and H4K16Ac. Importantly, a mutation in H3.3K36 that disrupts H3K36 methylation (H3.3K36R) does not rescue the H3.3 knockdown (KD) phenotype. In addition, H3.3 KD embryos have increased incorporation of linker H1. Knockdown of Mof (Kat8), an acetyltransferase specific for H4K16, similarly leads to excessive H1 incorporation. Remarkably, pan-H1 RNA interference (RNAi) partially rescues the chromosome condensation of H3.3 KD embryos and allows development to the blastocyst stage. These results reveal that H3.3 mediates a balance between open and condensed chromatin that is crucial for the fidelity of chromosome segregation during early mouse development.
Rac function is critical for cell migration but not required for spreading and focal adhesion formation
Authors: Steffen Anika , Ladwein Markus , Dimchev Georgi A. , Hein Anke , Schwenkmezger Lisa , Arens Stefan , Ladwein Kathrin I. , Holleboom J. Margit , Schur Florian , Small J. Victor , Schwarz Janett , Gerhard Ralf , Faix Jan , Stradal Theresia E. B. , Brakebusch Cord , Rottner Klemens
Published: August 2013

Cell migration is commonly accompanied by protrusion of membrane ruffles and lamellipodia. In 2D-migration, protrusion of these thin sheets of cytoplasm is considered both relevant to exploration of new space and initiation of nascent adhesion to the substratum. Lamellipodia formation can be potently stimulated by Rho GTPases of the Rac subfamily, but also by RhoG or Cdc42. Here we describe viable fibroblast cell lines genetically deficient for Rac1 that lack detectable levels of Rac2 and -3. Rac-deficient cells were devoid of apparent lamellipodia, which could be restored by expression of either Rac subfamily member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction in wound closure and random cell migration and a notable loss of sensitivity to a chemotactic gradient. Despite these defects, Rac deficient cells were able to spread, formed filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were mostly unaffected by genetic removal of Rac1. However, Rac deficiency increased the mobility of different components in focal adhesions, potentially explaining how Rac – although not essential - can contribute to focal adhesion assembly. Together, our data demonstrate that Rac signalling is essential for lamellipodia protrusion and for efficient cell migration, but not for spreading or filopodia formation. Our findings also suggest that Rac GTPases are crucial to the establishment or maintenance of polarity in chemotactic migration.
A novel PAR-1-binding protein, MTCL1, plays critical roles in organizing microtubules in polarizing epithelial cells
Authors: Sato Yoshinori , Akitsu Masashi , Amano Yoshiko , Yamashita Kazunari , Ide Mariko , Shimada Kyoko , Yamashita Akio , Hirano Hisashi , Arakawa Noriaki , Maki Takahisa , Hayashi Ikuko , Ohno Shigeo , Suzuki Atsushi
Published: August 2013

The establishment of epithelial polarity is tightly linked to the dramatic reorganization of microtubules (MTs) from a radial array to a vertical alignment of non-centrosomal MT bundles along the lateral membrane and a meshwork under the apical and basal membranes. However, little is known about the underlying molecular mechanism of this polarity-dependent MT remodeling. The evolutionarily conserved cell polarity-regulating kinase PAR-1, whose activity is essential for maintaining the dynamic state of MTs, plays indispensable roles to promote this process. Here, we identify a novel PAR-1-binding protein, named MTCL1 (Microtubule crosslinking factor 1), which crosslinks MTs through its N-terminal MT-binding region and subsequent coiled-coil motifs. MTCL1 colocalized with the apicobasal MT bundles in epithelial cells, and its knockdown impaired the development of these MT bundles and the epithelial cell specific columnar shape. Rescue experiments revealed that the N-terminal MT-binding region was indispensable for restoring these defects of the knockdown cells. MT regrowth assays indicated that MTCL1 was not required for the initial radial growth of MTs from the apical centrosome, but was essential for the accumulation of non-centrosomal MTs to the sublateral regions. Interestingly, MTCL1 recruited a subpopulation of PAR-1b to the apicobasal MT bundles, and its interaction with PAR-1b was required for MTCL1-dependent development of the apicobasal MT bundles. These results suggest that MTCL1 mediates the epithelial cell-specific reorganization of non-centrosomal MTs through its MT-crosslinking activity, and cooperates with PAR-1b to maintain the correct temporal balance between dynamic and stable MTs within the apicobasal MT bundles.