bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of Complex Osteochondral Lesions of the Talus With Cylindrical Sponge Allograft and Particulate Juvenile Cartilage Graft
Authors: Bleazey Scott , Brigido Stephen A.
Published: September 2012

Osteochondral lesions of the talus can be a challenging injury to treat for even the most experienced foot and ankle surgeon. Although the advances in imaging have made the diagnosis of chondral lesions more accurate, surgeons are still struggling to find ways to reliably treat advanced lesions with subchondral bone damage. This article looks at the use of allograft bone and particulate juvenile cartilage in patients with advanced subchondral bone damage and osteochondral lesions of the talus.

Levels of Evidence: Therapeutic, Level IV, Case series
The Emotional Origins of a Social Learning Bias
Authors: Martens Jason P. , Tracy Jessica L.
Published: August 2012

Humans learn, in large part, by copying knowledgeable others. However, because others can be deceitful or lack competence, indiscriminate copying would be maladaptive. How then do individuals determine which social group members have knowledge that should be copied? We argue that the pride nonverbal expression may signal expertise, and thus bias learning such that proud others are more likely to be copied. In two studies, financially motivated participants answered a difficult trivia question after viewing a photograph (Study 1A) or a video (Study 2) of an emotion-displaying confederate answering the same question. Pride-displaying confederates were copied significantly more frequently than those displaying other expressions, suggesting that pride expressions bias social learning. Study 1B demonstrated that this effect was restricted to participants who were financially motivated to acquire knowledge. These findings indicate that pride displays are functional for observers and may play a critical role in social learning.
Headache disorders: differentiating and managing the common subtypes
Authors: Ahmed Fayyaz
Published: August 2012

Headache is an extremely common symptom and collectively headache disorders are among the most common of the nervous system disorders, with a prevalence of 48.9% in the general population.1 Headache affects people of all ages, races and socioeconomic status and is more common in women. Some headaches are extremely debilitating and have significant impact on an individual’s quality of life, imposing huge costs to healthcare and indirectly to the economy in general. Only a small proportion of headache disorders require specialist input. The vast majority can be effectively treated by a primary care physician or generalist with correct clinical diagnosis that requires no special investigation. Primary headache disorders – migraine, tension headache and cluster headache – constitute nearly 98% of all headaches; however, secondary headaches are important to recognise as they are serious and may be life threatening. This article provides an overview of the most common headache disorders and discusses the red flag symptoms that help identify serious causes that merit urgent specialist referral. The current pathway of headache care in the UK is discussed with a view to proposing a model that might fit well in the financially constrained National Health Service (NHS) and with new NHS reforms. The role of the national society, the British Association for the Study of Headache, and the patient organisations such as Migraine Trust in headache education to the professionals and the general public in shaping headache care in the UK is described. The article concludes by summarising evidence-based management of common headache diagnoses.
Characterisation of transient oxide formation on NiCrAlY after heat treatment in vacuum
Authors: Huang X , Puetz P , Yang Q , Tang Z
Published: September 2012

To better understand transient oxide formation on the surface of standalone NiCrAlY in a vacuum, plasma sprayed NiCrAlY samples were subjected to a series of heat treatments at temperatures ranging from 1000 to 1100°C and for two different holding times. The morphology, composition and type of transient oxide(s) formed after heat treatment were characterised using scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction (XRD). All samples exhibited the formation of a top layer of discrete or island like Ni rich oxide in cellular shaped alumina. The alumina layer, although difficult to be detected in cross-section, was very dense and covered most of the coating surface. The transisent oxide formation on the heat treated surfaces was further analysed using XRD and α-Al2O3 was detected on all heat treated samples in addition to NiO and possible spinel. Cr2O3 seemed to be present on the samples heat treated at 1000 and 1050°C but not on the sample heat treated at 1100°C. Increased Al surface content, in comparison to the as sprayed sample, was found on all heat treated samples. High Al content, corresponding to the extent of alumina formation on heat treated samples, was observed for samples heat treated for a longer time as more oxygen diffusion took place. The coating surface Al content increased with heat treatment from 1000 to 1050°C and reduced from 1050 to 1100°C.
The clinical implication of SRSF2 mutation in patients with myelodysplastic syndrome and its stability during disease evolution
Authors: Wu Shang-Ju , Kuo Yuan-Yeh , Hou Hsin-An , Li Li-Yu , Tseng Mei-Hsuan , Huang Chi-Fei , Lee Fen-Yu , Liu Ming-Chih , Liu Chia-Wen , Lin Chien-Ting , Chen Chien-Yuan , Chou Wen-Chien , Yao Ming , Huang Shang-Yi , Ko Bor-Sheng , Tang Jih-Luh , Tsay Woei , Tien Hwei-Fang
Published: August 2012

Recurrent somatic mutation of SRSF2, one of the RNA splicing machinery genes, has been identified in a substantial proportion of patients with myelodysplastic syndrome (MDS). However, the clinical and biologic characteristics of MDS with this mutation remain to be addressed. In this study, 34 (14.6%) of the 233 MDS patients were found to have SRSF2 mutation. SRSF2 mutation was closely associated with male sex (P = .001) and older age (P < .001). It occurred concurrently with at least 1 additional mutation in 29 patients (85.3%) and was closely associated with RUNX1, IDH2, and ASXL1 mutations (P = .004, P < .001, and P < .001, respectively). Patients with SRSF2 mutation had an inferior overall survival (P = .010), especially in the lower risk patients. Further exploration showed that the prognostic impact of SRSF2 mutation might be attributed to its close association with old age. Sequential analyses in 173 samples from 66 patients showed that all SRSF2-mutated patients retained their original mutations, whereas none of the SRSF2-wild patients acquired a novel mutation during disease evolution. In conclusion, SRSF2 mutation is associated with distinct clinical and biologic features in MDS patients. It is stable during the clinical course and may play little role in disease progression.
Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity
Authors: Sangaletti Sabina , Tripodo Claudio , Chiodoni Claudia , Guarnotta Carla , Cappetti Barbara , Casalini Patrizia , Piconese Silvia , Parenza Mariella , Guiducci Cristiana , Vitali Caterina , Colombo Mario P.
Published: August 2012

Antineutrophil cytoplasmic antibodies (ANCAs) target proteins normally retained within neutrophils, indicating that cell death is involved in the autoimmunity process. Still, ANCA pathogenesis remains obscure. ANCAs activate neutrophils inducing their respiratory burst and a peculiar form of cell death, named NETosis, characterized by formation of neutrophil extracellular traps (NETs), decondensed chromatin threads decorated with cytoplasmic proteins endorsed with antimicrobial activity. NETs have been consistently detected in ANCA-associated small-vessel vasculitis, and this association prompted us to test whether the peculiar structure of NET favors neutrophil proteins uploading into myeloid dendritic cells and the induction of ANCAs and associated autoimmunity. Here we show that myeloid DCs uploaded with and activated by NET components induce ANCA and autoimmunity when injected into naive mice. DC uploading and autoimmunity induction are prevented by NET treatment with DNAse, indicating that NET structural integrity is needed to maintain the antigenicity of cytoplasmic proteins. We found NET intermingling with myeloid dendritic cells also positive for neutrophil myeloperoxidase in myeloperoxidase-ANCA-associated microscopic poliangiitis providing a potential correlative picture in human pathology. These data provide the first demonstration that NET structures are highly immunogenic such to trigger adaptive immune response relevant for autoimmunity.
NKT cell adjuvant-based tumor vaccine for treatment of myc oncogene-driven mouse B-cell lymphoma
Authors: Mattarollo Stephen R. , West Alison C. , Steegh Kim , Duret Helene , Paget Christophe , Martin Ben , Matthews Geoffrey M. , Shortt Jake , Chesi Marta , Bergsagel P. Leif , Bots Michael , Zuber Johannes , Lowe Scott W. , Johnstone Ricky W. , Smyth Mark J.
Published: August 2012

Immunomodulators are effective in controlling hematologic malignancy by initiating or reactivating host antitumor immunity to otherwise poorly immunogenic and immune suppressive cancers. We aimed to boost antitumor immunity in B-cell lymphoma by developing a tumor cell vaccine incorporating α-galactosylceramide (α-GalCer) that targets the immune adjuvant properties of NKT cells. In the Eμ-myc transgenic mouse model, single therapeutic vaccination of irradiated, α-GalCer–loaded autologous tumor cells was sufficient to significantly inhibit growth of established tumors and prolong survival. Vaccine-induced antilymphoma immunity required NKT cells, NK cells, and CD8 T cells, and early IL-12–dependent production of IFN-γ. CD4 T cells, gamma/delta T cells, and IL-18 were not critical. Vaccine treatment induced a large systemic spike of IFN-γ and transient peripheral expansion of both NKT cells and NK cells, the major sources of IFN-γ. Furthermore, this vaccine approach was assessed in several other hematopoietic tumor models and was also therapeutically effective against AML-ETO9a acute myeloid leukemia. Replacing α-GalCer with β-mannosylceramide resulted in prolonged protection against Eμ-myc lymphoma. Overall, our results demonstrate a potent immune adjuvant effect of NKT cell ligands in therapeutic anticancer vaccination against oncogene-driven lymphomas, and this work supports clinical investigation of NKT cell–based immunotherapy in patients with hematologic malignancies.
Cdc42 regulates neutrophil migration via crosstalk between WASp, CD11b, and microtubules
Authors: Kumar Sachin , Xu Juying , Perkins Charles , Guo Fukun , Snapper Scott , Finkelman Fred D. , Zheng Yi , Filippi Marie-Dominique
Published: August 2012

Chemotaxis promotes neutrophil participation in cellular defense by enabling neutrophil migration to infected tissue and is controlled by persistent cell polarization. One long-standing question of neutrophil polarity has been how the pseudopod and the uropod are coordinated. In our previous report, we suggested that Rho GTPase Cdc42 controls neutrophil polarity through CD11b signaling at the uropod, albeit through an unknown mechanism. Here, we show that Cdc42 controls polarity, unexpectedly, via its effector WASp. Cdc42 controls WASp activation and its distant localization to the uropod. At the uropod, WASp regulates the reorganization of CD11b integrin into detergent resistant membrane domains; in turn, CD11b recruits the microtubule end binding protein EB1 to capture and stabilize microtubules at the uropod. This organization is necessary to maintain neutrophil polarity during migration and is critical for neutrophil emigration into inflamed lungs. These results suggest unrecognized mechanism of neutrophil polarity in which WASp mediates long-distance control of the uropod by Cdc42 to maintain a proper balance between the pseudopod and the uropod. Our study reveals a new function for WASp in the control of neutrophil polarity via crosstalk between CD11b and microtubules.
Massive evolution of the immunoglobulin heavy chain locus in children with B precursor acute lymphoblastic leukemia
Authors: Gawad Charles , Pepin Francois , Carlton Victoria E. H. , Klinger Mark , Logan Aaron C. , Miklos David B. , Faham Malek , Dahl Gary , Lacayo Norman
Published: August 2012

The ability to distinguish clonal B-cell populations based on the sequence of their rearranged immunoglobulin heavy chain (IgH) locus is an important tool for diagnosing B-cell neoplasms and monitoring treatment response. Leukemic precursor B cells may continue to undergo recombination of the IgH gene after malignant transformation; however, the magnitude of evolution at the IgH locus is currently unknown. We used next-generation sequencing to characterize the repertoire of IgH sequences in diagnostic samples of 51 children with B precursor acute lymphoblastic leukemia (B-ALL). We identified clonal IgH rearrangements in 43 of 51 (84%) cases and found that the number of evolved IgH sequences per patient ranged dramatically from 0 to 4024. We demonstrate that the evolved IgH sequences are not the result of amplification artifacts and are unique to leukemic precursor B cells. In addition, the evolution often follows an allelic exclusion pattern, where only 1 of 2 rearranged IgH loci exhibit ongoing recombination. Thus, precursor B-cell leukemias maintain evolution at the IgH locus at levels that were previously underappreciated. This finding sheds light on the mechanisms associated with leukemic clonal evolution and may fundamentally change approaches for monitoring minimal residual disease burden.
Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses
Authors: Lannes Nils , Python Sylvie , Summerfield Artur
Published: August 2012

Foot-and-mouth disease virus (FMDV) is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses.
Microbial diversity and anaerobic hydrocarbon degradation potential in an oil-contaminated mangrove sediment
Authors: Andrade Luiza L , Leite Deborah CA , Ferreira Edir M , Ferreira Lívia Q , Paula Geraldo R , Maguire Michael J , Hubert Casey RJ , Peixoto Raquel S , Domingues Regina MCP , Rosado Alexandre S
Published: August 2012

Background

Mangrove forests are coastal wetlands that provide vital ecosystem services and serve as barriers against natural disasters like tsunamis, hurricanes and tropical storms. Mangroves harbour a large diversity of organisms, including microorganisms with important roles in nutrient cycling and availability. Due to tidal influence, mangroves are sites where crude oil from spills farther away can accumulate. The relationship between mangrove bacterial diversity and oil degradation in mangrove sediments remains poorly understood.

Results

Mangrove sediment was sampled from 0–5, 15–20 and 35–40 cm depth intervals from the Suruí River mangrove (Rio de Janeiro, Brazil), which has a history of oil contamination. DGGE fingerprinting for bamA, dsr and 16S rRNA encoding fragment genes, and qPCR analysis using dsr and 16S rRNA gene fragment revealed differences with sediment depth.

Conclusions

Analysis of bacterial 16S rRNA gene diversity revealed changes with depth. DGGE for bamA and dsr genes shows that the anaerobic hydrocarbon-degrading community profile also changed between 5 and 15 cm depth, and is similar in the two deeper sediments, indicating that below 15 cm the anaerobic hydrocarbon-degrading community appears to be well established and homogeneous in this mangrove sediment. qPCR analysis revealed differences with sediment depth, with general bacterial abundance in the top layer (0–5 cm) being greater than in both deeper sediment layers (15–20 and 35–40 cm), which were similar to each other.
Association between sedentary behaviour and socioeconomic factors, diet and lifestyle among the Balearic Islands adolescents
Authors: Bibiloni Maria del Mar , Pich Jordi , Córdova Alfredo , Pons Antoni , Tur Josep A
Published: August 2012

Background

Many different factors influenced food habits and physical activity patterns of adolescents in a complex interactive way. The aim of this study was to assess association between sedentary behaviour and socioeconomic factors, diet and lifestyle among the Balearic Islands adolescents.

Methods

A cross-sectional survey (n = 1961; 12–17 years old) was carried out. Physical activity was assessed using the International Physical Activity Questionnaire for adolescents (IPAQ-A). Sedentary behaviour was defined as <300 min/week of moderate and vigorous physical activity. Anthropometric measurements, body image, socio-economic and lifestyle determinants, food consumption, and adherence to the Mediterranean diet were assessed.

Results

The prevalence of sedentary behaviour was 37.1% (22.0% boys, 50.8% girls). Active boys consumed frequently breakfast cereals and fresh fruit; active girls yogurt, cheese, breakfast cereals, and fresh fruit; and sedentary girls high fat foods and soft drinks. Sedentary behaviour of girls was directly associated to age, and time spent on media screen and homework, and inversely related to adherence to Mediterranean diet, and body composition. Sedentary behaviour of boys was inversely related to adherence to the Mediterranean diet, and the desire to remain the same weight.

Conclusions

The prevalence of sedentary behaviour among Balearic Islands adolescents is high, mainly among girls. Age, sex, parental educational and profession levels, body size dissatisfaction, and poor quality diet are important factors of physical activity practice among adolescents.
Vocal fold composition and early glottic carcinoma infiltration
Authors: Fang Qin , Wang Yang , Zhao Xiaoyan , Cao Luhong , Sun Na , Tan Xuejun , Wu Lide , Sun Guangbin
Published: August 2012

Background

Current imaging techniques provide only limited information pertaining to the extent of infiltration of laryngeal carcinomas into vocal fold tissue layers. Therefore, it is needed to seek the contribute to the body of knowledge surrounding examination and characterization in laryngeal carcinoma infiltration.

Methods

Excised larynges were collected from 30 male laryngectomy patients with an average age of 43.5 years (ranging 36 to 55 years) and history of smoking (≥10 years) exhibiting T1, T2, or subglottal (normal vocal fold) carcinomas. Vocal folds were preserved via freezing or immersion in paraffin. The depth of the mucosa, submucosa, and muscular layers in both normal vocal folds and tumor tissues of afflicted vocal folds was measured.

Results

The average depths of the mucosa, submucosa, and muscular layers in normal vocal folds were 0.15 ± 0.06 mm, 2.30 ± 0.59 mm, and 2.87 ± 0.88 mm, respectively. Infiltration measurements of T1 tumors showed a depth of 1.62 ± 0.51 mm and 1.32 ± 0.49 mm in frozen sections and paraffin-embedded samples, respectively. Similarly, T2 tumors showed a depth of 2.87 ± 0.68 mm and 2.58 ± 0.67 mm in frozen sections and paraffin-embedded samples, respectively. T1 and T2 tumors occupied 24.8 ± 10 and 48.5 ± 15 percent of the normal vocal fold depth, respectively.

Conclusion

This data provides a baseline for estimating infiltration of laryngeal carcinomas in vocal fold tissue layers, of particular interest to surgeons. This information may be used to assess typical depths of infiltration, thus allowing for more appropriate selection of surgical procedures based on individual patient assessment.
Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models
Authors: Wu Xianhua , Zhang Jingchuan , Zhen Ruheng , Lv Jing , Zheng Li , Su Xinying , Zhu Guanshan , Gavine Paul R , Xu Songtao , Lu Shaohua , Hou Jun , Liu Yalan , Xu Chen , Tan Yunshan , Xie Liang , Yin Xiaolu , He Deming , Ji Qunsheng , Hou Yingyong , Ge Di
Published: August 2012

Background

Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models.

Methods

PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC) tissues into immunodeficient (SCID/nude) mice. HER-2 gene copy number (GCN) and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group). Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient’s ESCC tissues. Similarity between the PDECX models and their corresponding patient’s ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation.

Results

None of the PDECX models (or their corresponding patient’s ESCC tissues) harboredHER-2gene amplification. IHC staining showed HER-2 positivity (IHC 2+) in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+). A second HER-2 positive (IHC 2+) model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model.

Conclusions

This study demonstrates Trastuzumab-induced tumor regressions in HER-2 positive tumors, and highlights PIK3CA mutation as a potential resistance mechanism to Trastuzumab treatment in pre-clinical patient-derived EC xenograft models.
Detection of tampered region for JPEG images by using mode-based first digit features
Authors: Li Xiang Hua , Zhao Yu Qian , Liao Miao , Shih Frank Y , Shi Yun Q
Published: August 2012

With the widespread availability of image editing software, digital images have been becoming easy to manipulate and edit even for non-professional users. For a tampered Joint Photographic Experts Group (JPEG) image, the tampered region usually has different JPEG compression history from the authentic region, which can be used to detect and locate the tampered region. In this article, we propose to apply the statistical features of the first digits of individual alternate current modes and support vector machine to detect and locate the tampered region. Experimental results show that our proposed method is effective for detecting three popularly used image manipulations. Its expectation of the percentage of overlap between the detected tampered region and the truth tampered region is higher than the existing algorithms.
Spatiotemporal Dynamics of Re-Innervation and Hyperinnervation Patterns by Uninjured CGRP Fibers in the Rat Foot Sole Epidermis after Nerve Injury
Authors: Duraku Liron S , Hossaini Mehdi , Hoendervangers Sieske , Falke Lukas L , Kambiz Shoista , Mudera Vivek C , Holstege Joan C , Walbeehm Erik T , Ruigrok Tom J H
Published: August 2012

The epidermis is innervated by fine nerve endings that are important in mediating nociceptive stimuli. However, their precise role in neuropathic pain is still controversial. Here, we have studied the role of epidermal peptidergic nociceptive fibers that are located adjacent to injured fibers in a rat model of neuropathic pain. Using the Spared Nerve Injury (SNI) model, which involves complete transections of the tibial and common peroneal nerve while sparing the sural and saphenous branches, mechanical hypersensitivity was induced of the uninjured lateral (sural) and medial (saphenous) area of the foot sole. At different time points, a complete foot sole biopsy was taken from the injured paw and processed for Calcitonin Gene-Related Peptide (CGRP) immunohistochemistry. Subsequently, a novel 2D-reconstruction model depicting the density of CGRP fibers was made to evaluate the course of denervation and re-innervation by uninjured CGRP fibers. The results show an increased density of uninjured CGRP-IR epidermal fibers on the lateral and medial side after a SNI procedure at 5 and 10 weeks. Furthermore, although in control animals the density of epidermal CGRP-IR fibers in the footpads was lower compared to the surrounding skin of the foot, 10 weeks after the SNI procedure, the initially denervated footpads displayed a hyper-innervation. These data support the idea that uninjured fibers may play a considerable role in development and maintenance of neuropathic pain and that it is important to take larger biopsies to test the relationship between innervation of injured and uninjured nerve areas.
Comparison of bone marrow and adipose tissue-derived canine mesenchymal stem cells
Authors: Takemitsu Hiroshi , Zhao Dongwei , Yamamoto Ichiro , Harada Yasuji , Michishita Masaki , Arai Toshiro
Published: September 2012

Background

Bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs) are potential cellular sources of therapeutic stem cells. MSCs are a multipotent population of cells capable of differentiating into a number of mesodermal lineages. Treatment using MSCs appears to be a helpful approach for structural restoration in regenerative medicine. Correct identification of these cells is necessary, but there is inadequate information on the MSC profile of cell surface markers and mRNA expression in dogs. In this study, we performed molecular characterization of canine BM-MSCs and AT-MSCs using immunological and mRNA expression analysis.

Results

Samples were confirmed to be multipotent based on their osteogenic and adipogenic differentiation. And these cells were checked as stem cell, hematopoietic and embryonic stem cell (ESC) markers by flow cytometry. BM- and AT-MSCs showed high expression of CD29 and CD44, moderate expression of CD90, and were negative for CD34, CD45, SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81. SSEA-1 was expressed at very low levels in AT-MSCs. Quantitative real-time PCR (qRT-PCR) revealed expression of Oct3/4, Sox2, and Nanog in BM- and AT-MSCs. There was no significant difference in expression of Oct3/4 and Sox2 between BM-MSCs and AT-MSCs. However, Nanog expression was 2.5-fold higher in AT-MSCs than in BM-MSCs. Using immunocytochemical analysis, Oct3/4 and Sox2 proteins were observed in BM- and AT-MSCs.

Conclusion

Our results provide fundamental information to enable for more reproducible and reliable quality control in the identification of canine BM-MSCs and AT-MSCs by protein and mRNA expression analysis.
Courtship behaviour of Phlebotomus papatasi the sand fly vector of cutaneous leishmaniasis
Authors: Chelbi Ifhem , Bray DP , Hamilton JGC
Published: August 2012

Background

The sand fly Phlebotomus papatasi is an Old World vector of Leishmania major, the etiologic agent of zoonotic cutaneous leishmaniasis. This study describes the courtship behaviour of P. papatasi and compares it with that of Lutzomyia longipalpis, the New World vector of visceral leishmaniasis. Understanding the details of courtship behaviour in P. papatasi may help us to understand the role of sex pheromones in this important vector.

Results

P. papatasi courtship was found to start with the female touching the male, leading him to begin abdomen bending and wing flapping. Following a period of leg rubbing and facing, the male flaps his wings while approaching the female. The female then briefly flaps her wings in response, to indicate that she is willing to mate, thereby signaling the male to begin copulation. Male P. papatasi did not engage in parading behaviour, which is performed by male L. longipalpis to mark out individual territories during lekking (the establishment and maintenance of mating aggregations), or wing-flap during copulation, believed to function in the production of audio signals important to mate recognition. In P. papatasi the only predictor of mating success for males was previous copulation attempts and for females stationary wing-flapping. By contrast, male L. longipalpis mating success is predicted by male approach-flapping and semi-circling behaviour and for females stationary wing-flapping.

Conclusions

The results show that there are important differences between the mating behaviours of P. papatasi and L. longipalpis. Abdomen bending, which does not occur in L. longipalpis, may act in the release of sex pheromone from an as yet unidentified site in the male abdomen. In male L. longipalpis wing-flapping is believed to be associated with distribution of male pheromone. These different behaviours are likely to signify significant differences in how pheromone is used, an observation that is consistent with field and laboratory observations.
Assessment of the vaccine industry in Iran in context of accession to WTO: a survey study
Authors: Hashemi Meshkini Amir , Kebriaeezadeh Abbas , Dinarvand Rasoul , Nikfar Shekoufeh , Habibzadeh MohammadGafar , Vazirian Iman
Published: August 2012

Background

The vaccine industry is one of the most important health-related industries. It can be affected by accession to the World Trade Organization (WTO) because of probable dramatic changes in the business environment. Iran has already initiated accession negotiations.

Purpose of the study

In this paper, we investigate the position of, challenges to, and opportunities for vaccine manufacturing in Iran with regard to accession to the WTO.

Methods

This is a qualitative and cross sectional study. To collect information, we designed a questionnaire and interviewed some of the vaccine industry’s key opinion leaders in Iran. Before the interviews were conducted, the questionnaires were sent to these individuals by email.

Results

According to the interviewees, the country’s main challenges with regard to accession to the WTO are the lack of firm internal intellectual property (IP) rules, not being recognized as pre-qualified by the World Health Organization (WHO), the use of old equipment, and a lack of cooperation with global vaccine companies.

Major conclusions

Iran’s local vaccine industry, with a long history and international reputation that could be used as an advantage, is faced with several challenges, such as problems with keeping up with Current Good Manufacturing Practice (cGMP), a lack of adequate and meaningful investment in research and development (R&D), and limitations on private sector participation in the production of vaccines.

Gradual privatization of the industry, improved international relations, utilization of the R&D power of small hi-tech companies, consistent education of human resources, and modernization of infrastructures and equipment are among the suggested solutions.
Report of methamphetamine use and cardiomyopathy in three patients
Authors: Sadeghi Roxana , Agin Khosro , Taherkhani Maryam , Najm-Afshar Leila , Nelson Lewis S , Abdollahi Mohammad , Shadnia Shahin
Published: August 2012

Background

Methamphetamine (meth) is a stimulant used illegally around the world, including in Iran. Cardiomyopathy and cardiac failure may occur following chronic meth use and may cause the patients referred to the emergency department.

Case reports

A 28-year old man and two women, ages 29 and 31-year-old, with a history of meth use, were admitted to the emergency department with severe dyspnea at rest. Each had sinus tachycardia with tachypnea and an echocardiogram that showed severe systolic dysfunction consistent with heart failure. Additional evaluation in the hospital revealed cardiomyopathy with no other etiology other than the meth use.

Conclusion

There are several reports that show an increase in frequency of meth use, suggesting that cardiomyopathy and acute heart failure may be a new medical concern.
Regulation of osteoclast structure and function by FAK family kinases
Authors: Ray Brianne J , Thomas Keena , Huang Cynthia S , Gutknecht Michael F , Botchwey Edward A , Bouton Amy H
Published: September 2012

Regulation of distinct and overlapping functions of FAK family kinases in osteoclasts.

Osteoclasts are highly specialized cells that resorb bone and contribute to bone remodeling. Diseases such as osteoporosis and osteolytic bone metastasis occur when osteoclast-mediated bone resorption takes place in the absence of concurrent bone synthesis. Considerable effort has been placed on identifying molecules that regulate the bone resorption activity of osteoclasts. To this end, we investigated unique and overlapping functions of members of the FAK family (FAK and Pyk2) in osteoclast functions. With the use of a conditional knockout mouse model, in which FAK is selectively targeted for deletion in osteoclast precursors (FAKΔmyeloid), we found that loss of FAK resulted in reduced bone resorption by osteoclasts in vitro, coincident with impaired signaling through the CSF-1R. However, bone architecture appeared normal in FAKΔmyeloid mice, suggesting that Pyk2 might functionally compensate for reduced FAK levels in vivo. This was supported by data showing that podosome adhesion structures, which are essential for bone degradation, were significantly more impaired in osteoclasts when FAK and Pyk2 were reduced than when either molecule was depleted individually. We conclude that FAK contributes to cytokine signaling and bone resorption in osteoclasts and partially compensates for the absence of Pyk2 to maintain proper adhesion structures in these cells.
The Moccasin Telegraph: Sign-Talk Autobiography and Pretty-shield, Medicine Woman of the Crows
Authors: Yandell Kay
Published: August 2012

In 1931, Crow medicine woman Pretty Shield delivered her oral autobiography to Frank Linderman, simultaneously through an interpreter of spoken Crow, and without translation to Linderman in Indian Sign Language. Pretty Shield’s and Linderman’s use of the sign language within this autobiography, coupled with Pretty Shield’s explanations of historical use of the sign language among precontact Crow people, suggests new views of various critical problems within the hybrid genre of American Indian autobiography, of which this text is one example. Pretty Shield’s husband, Goes Ahead, used the sign language to scout for General George Armstrong Custer at the 1876 Battle of the Little Bighorn; Pretty Shield’s account of the sign language in this battle additionally provides a rare and understudied interpretation of the Battle of the Little Bighorn, and of the larger American frontier histories in which sign talk played a significant role.
Jazz, Black Transnationalism, and the Political Aesthetics of Langston Hughes’s Ask Your Mama
Authors: Lowney John
Published: August 2012

Lowney’s essay examines how Langston Hughes’s cultural work in the 1950s and early 1960s illustrates the challenge of developing a progressive black transnationalist literary culture. It concentrates especially on Hughes’s longest and most ambitious poem, Ask Your Mama: 12 Moods for Jazz (1961), which renders his dual commitment to a black transnationalist public and an innovative African diaspora jazz poetics. Ask Your Mama features the interaction of African cultures in the Americas and Africa, with its evocation of Afro-Caribbean as well as African American music and its movement among different sites of black revolutionary struggle. In this context, jazz plays an explicitly political role in expressing the revolutionary desire for black liberation in the United States, Africa, and the Caribbean. This is most evident in the opening mood of Ask Your Mama, “Cultural Exchange,” which introduces the black transnationalist network of musical forms, proper names, and social locations that reverberate throughout the poem. Lowney’s essay discusses the implications of Hughes’s ironic allusion to the “cultural exchange” of African American “jazz ambassadors,” who were funded by the US State Department to perform in Africa in the 1950s. In doing so, it draws from recent research in jazz studies by Penny Von Eschen and Ingrid Monson to underscore the historical complexity and political incisiveness of Hughes’s enactment of a black transnationalist public in the poem.
Erg is a crucial regulator of endocardial-mesenchymal transformation during cardiac valve morphogenesis
Authors: Vijayaraj Preethi , Le Bras Alexandra , Mitchell Nora , Kondo Maiko , Juliao Saul , Wasserman Meredith , Beeler David , Spokes Katherine , Aird William C. , Baldwin H. Scott , Oettgen Peter
Published: August 2012

During murine embryogenesis, the Ets factor Erg is highly expressed in endothelial cells of the developing vasculature and in articular chondrocytes of developing bone. We identified seven isoforms for the mouse Erg gene. Four share a common translational start site encoded by exon 3 (Ex3) and are enriched in chondrocytes. The other three have a separate translational start site encoded by Ex4 and are enriched in endothelial cells. Homozygous ErgΔEx3/ΔEx3 knockout mice are viable, fertile and do not display any overt phenotype. By contrast, homozygous ErgΔEx4/ΔEx4 knockout mice are embryonic lethal, which is associated with a marked reduction in endocardial-mesenchymal transformation (EnMT) during cardiac valve morphogenesis. We show that Erg is required for the maintenance of the core EnMT regulatory factors that include Snail1 and Snail2 by binding to their promoter and intronic regions.
Biomechanical determinants of transverse and rotary gallop in cursorial mammals
Authors: Biancardi Carlo Massimo , Minetti Alberto Enrico
Published: August 2012

Transverse and rotary gallop differ for the placement of the hind and fore leading feet: ipsilateral in the former, contralateral in the latter gait. 351-filmed sequences have been analysed to assess the gallop type of 89 investigated mammal species belonging to Carnivora, Artiodactyla and Perissodactyla orders. 23 biometrical, ecological and physiological parameters have been collected for each species both from literature data and from animal specimens. Most of the species showed only one kind of gallop: transverse (42%) or rotary (39%), while some species performed rotary gallop only at high speed (19%). In a factorial analysis the first principal component (PC), which accounted for 40% of the total variance, was positively correlated to the relative speed and negatively correlated to size and body mass. The second PC was correlated to the ratio between distal and proximal limb segments. Large size and longer proximal limb segments resulted associated to transverse gallop, while rotary and speed dependent species showed higher metacarpus/humerus and metatarsus/femur length ratio and faster relative speeds. The limb excursion angles resulted proportional to the square-root of the Froude number, and significantly higher in rotary galloper. The gait pattern analysis provided significant differences between transverse and rotary gallop in fore and hind duty factor (t-test; p < 0.001), and in duration of the fore contact (t-test; P = 0.045). Our results assessed that an exclusive gallop gait is adopted by a large number of mammal species, and indicated that the gallop pattern depends on diverse environmental, morphometrical and biomechanical characters.
Does immune suppression during stress occur to promote physical performance?
Authors: Martin Lynn B. , Brace Amber , Urban Alexandra , Coon Courtney AC , Liebl Andrea L
Published: August 2012

Two adaptationist hypotheses have been proposed to explain why stress, particularly elevation of stress hormones (i.e., glucocorticoids), tends to suppress immune functions. One is that immune suppression represents efforts to minimize autoimmune responses to self-antigens released as organisms cope with stressors (i.e., the autoimmune-avoidance hypothesis). The other is that immune suppression occurs to promote a shunting of resources to life processes more conducive to survival of the stressor (i.e., the re-allocation hypothesis). Here in wild-caught house sparrows (Passer domesticus), we tested the second hypothesis, asking whether sustained elevation of baseline glucocorticoids, due to captivity, caused a greater rate of decline in immune functions than flight performance. A greater decline in immune functions than flight performance would support the re-allocation hypothesis. As in previous studies, we found that captivity tended to alter baseline corticosterone, suggesting that house sparrows experience captivity as a stressor. Captivity also affected several constitutive and induced innate immune metrics: bacterial (Escherichia coli) killing activity (BKA) of blood and oxidative burst of leukocytes both changed in a manner consistent with immune disregulation. In contrast, breast muscle size and vertical flight (hovering) duration improved over captivity. Collectively, these changes provide indirect support for the re-allocation hypothesis, although within individuals, changes in immune and physical performance were unrelated.
Evaluation of a telemedical care programme for patients with Parkinson's disease
Authors: Marzinzik Frank , Wahl Michael , Doletschek Christoph M , Jugel Constanze , Rewitzer Charlotte , Klostermann Fabian
Published: September 2012

We reviewed a telemedicine-based care model for drug optimization in Parkinson's disease. In this model patients send video recordings made in the home to the treating team via the Internet. These serve as the basis for making therapeutic decisions, in particular drug adjustments. Data from 78 patients were analysed with respect to outcome, method acceptance and management of the procedure. During the 30-day telemedicine programme, the patients recorded an average of 3.2 videos per day. The patients’ motor score on the Unified Parkinson's Disease Rating Scale (UPDRS) was 31 points at enrolment and three months after ICP termination it was significantly lower at 24 points ( P < 0.01), i.e. there was less impairment. The patients rated their condition better at the end than at the beginning of the programme: on a 6-point scale, the mean rating at the beginning was 3.2 and the mean rating at the end was 2.8 ( P < 0.001). A blinded investigator rated the patients’ videos on the same scale: at the beginning the mean score was 3.0 and at the end it was 2.8 ( P < 0.05). The information from the questionnaire showed overall acceptance and practicability of the method. Both patients’ and neurologists’ use of the method was high. The method seems to be feasible for therapy optimization in Parkinson's disease, and of particular interest for patients with complex conditions who do not necessarily have to undergo hospital treatment.
Suitability of an electronic reminder device for measuring drug adherence in elderly patients with complex medication
Authors: Harbig Philipp , Barat Ishay , Damsgaard Else M
Published: September 2012

We evaluated an electronic reminder device for detecting non-adherence in elderly patients with complex medication regimens. Randomly selected, home-living elderly patients were studied. The patients were aged over 65 years and were taking more than four drugs. Patients received an electronic reminder device which contained a GSM communications module. They were visited three times over a one-year period by a nurse who counted their medicine supply. We compared the adherence measured by the electronic device with the actual adherence measured by the pill count. Almost half of the 315 patients dropped out of the study for various reasons, so the calculations were performed on 168 patients. The adherence measured by the electronic reminder system was 79% and was 92% measured by pill count ( P<0.0001). The limits of agreement estimated by a Bland-Altman analysis were −57 to +30. We also compared electronically measured adherence at morning/evening intake times with pill count adherence in the morning/evening only. For the pill count, there was almost no difference between morning and evening adherence rates (93%). For electronic measurement, adherence rates were lower in the evening (75%) than in the morning (81%). Electronic reminders were less reliable than the pill count in measuring adherence. However, the electronic system may be a useful supplement to other, more time consuming methods for measuring adherence.
An online positive parenting skills programme for paediatric traumatic brain injury: feasibility and parental satisfaction
Authors: Antonini Tanya N , Raj Stacey P , Oberjohn Karen S , Wade Shari L
Published: September 2012

We examined the feasibility of and parental satisfaction with a training programme for parents with children who had suffered traumatic brain injury (TBI). Families who did not have a home computer and/or webcam were loaned the necessary equipment. Skype was used for videoconferencing. After the initial treatment session in the family's home, the remaining nine sessions were conducted online. Each session had two parts: (1) a self-guided web session with information about a particular skill; (2) a videoconference session with the therapist. Three of the 20 families (15%) dropped out prior to the final 6-month follow-up visit. Of the remaining 17 families, 13 (65% of those enrolled) completed 9–14 sessions. Almost all of the caregivers (87%) said that the Skype sessions were helpful compared to a conventional office visit. Almost all parents were satisfied with the programme and the technology that was used. Parental satisfaction with the programme was not influenced by prior computer ownership or comfort with technology. The programme appears to be feasible for a wide range of parents of children with TBI and provides an alternative to conventional office-based sessions that may not be accessible to all families.
Minors or suspects? A discussion of the legal and ethical issues surrounding the indefinite storage of DNA collected from children aged 10–18 years on the National DNA Database in England and Wales
Authors: Mansel Charlotte , Davies Sharon
Published: September 2012

There are currently over 250,000 children between the ages of 10 and 18 years who have their genetic information stored on the National DNA Database. This paper explores the legal and ethical issues surrounding this controversial subject, with particular focus on juvenile capacity and the potential results of criminalizing young children and adolescents. The implications of the adverse legal judgement of the European Court of Human Rights in S and Marper v UK (2008) and the violation of Article 8 of the Convention are discussed. The authors have considered the requirement to balance the rights of the individual, particularly those of minors, against the need to protect the public and have compared the position in Scotland to that of the rest of the UK. The authors conclude that a more ethically acceptable alternative could be the creation of a separate forensic database for children aged 10–18 years, set up to safeguard the interests of those who have not been convicted of any crime.