Focal cartilage injury occurs commonly and often precipitates OA. Mesenchymal stem cells (MSCs) may be useful for repairing cartilage lesions, thereby preventing joint degeneration. Although MSCs isolated from bone marrow have been shown to have chondrogenic potential, synovial membrane-derived MSCs (SM-MSCs) may have superior chondrogenic abilities due to a common progenitor cell between synovium and cartilage. The objective of this study was to directly compare the immunophenotype, proliferative capabilities, and chondrogenic potential of equine SM-MSCs and bone marrow-derived MSCs (BM-MSCs). In order to do this, MSCs were isolated from synovial membrane and bone marrow collected from 6 adult horses. Flow cytometric analysis was used to assess cell surface marker expression including CD29, CD44, CD90, CD105, CD45, CD-79α, MHCI, and MHCII. Proliferation rates and doubling time were quantified in P1 and P2 cells. Trilineage differentiation assays were performed. MSC pellets were cultured in chondrogenic induction media for 28 days. Pellets were stained with toluidine blue to assess proteoglycan deposition. Expression of the chondrogenic-related genes ACAN, COL2b, and SOX9 was quantified using qRT-PCR. The immunophenotypes of BM-MSCs and SM-MSCs were similar with both cell types being positive for expression of stem cell markers (CD29, CD44, CD90, CD105, and MHCI) and negative for exclusion markers (CD45 and CD79α). Although SM-MSCs did not express the exclusion marker, MHCII, expression of MHCII was moderate in BM-MSCs. Overall, chondrogenic differentiation was not significantly between the cell types with histologic parameters, proteoglycan content and gene expression being similar. BM-MSCs showed enhanced osteogenic differentiation compared to SM-MSCs. Synovial membrane is a feasible source of MSCs in the horse, however, superior chondrogenesis in vitro should not be expected under currently described culture conditions.

In 2012 the Reassessment Campaign on Veterinary Resuscitation (RECOVER) published evidence-based treatment recommendations for dogs and cats with cardiopulmonary arrest (CPA), to optimize the clinical practice of small animal CPR and positively impact outcomes. Six years after the release of these guidelines, we aimed to determine the compliance of small animal veterinary CPR practices with these RECOVER guidelines. To identify current CPR practices in clinically active small animal veterinarians and their awareness of the RECOVER guidelines, we conducted an internet-based survey. Survey invitations were disseminated internationally via veterinary professional organizations and their social media outlets. Questions explored respondent demographics, CPR preparedness, BLS and ALS techniques and awareness of RECOVER guidelines. Responding small animal veterinarians (n = 770) in clinical practice were grouped by level of expertise: board-certified specialists (BCS, n = 216) and residents (RES, n = 69) in anesthesia or emergency and critical care, practitioners in emergency (GPE, n = 299) or general practice (GPG, n = 186). Large disparities in preparedness measures, BLS and ALS techniques emerged among levels of expertise. Only 32% (95% CI: 29-36%) of respondents complied with BLS practice guidelines, varying from 49% (95% CI: 42-55%) of BCS to 15% (95% CI: 10-20%) of GPG. While incompliances in BCS, RES, and GPE were predominantly due to knowledge gaps, GPG compliance was further compromised by limitations in the resuscitation environment (e.g., defibrillator availability, team size). Those aware of RECOVER guidelines (100% of BCS and RES; 77% of GPE; 35% of GPG) were more likely to comply with recommended preparedness (OR = 2.4; 95% CI: 1.2-4.8), BLS (OR = 4.5; 95% CI: 2.4-9.1), and ALS techniques (OR = 7.8; 95% CI: 2.4-9.1) independent of age, gender, region of practice or level of expertise. We conclude that awareness of RECOVER guidelines is high in specialists and residents, but incomplete among general practitioners. This awareness positively influenced compliance with CPR guidelines, but CPR practices continue to be variable and largely not in agreement with guidelines. A widely accessible educational strategy is required to broadly improve compliance with best practices in small animal CPR.

Ulnar collateral ligament (UCL) reconstruction, distal biceps tendon repair, and elbow arthroscopic surgery are common elbow procedures performed in active patients.

Both external and internal surfaces of organs (e.g., skin, mouth, gut, and intestine) are covered with bacteria, which often contribute to physiological events in host animals. Despite externally opened organs, the presence of bacteria in the mammalian female reproductive tract is uncertain. Here we assessed this problem using wild-type strains of mice, C57BL/6N and ICR. We first demonstrated that bacterial colonies were formed from the oviductal fluid in the C57BL/6N mice with birth experience ("parous"), but not in the mice without birth experience ("non-parous"). Sequence analysis of 16S ribosomal RNA (rRNA) revealed that Staphylococcus epidermidis existed in the oviductal fluid of the parous mice, confirmed by immunohistochemical analysis. Furthermore, extinction of bacterial population with intraperitoneal injection of antibiotics, penicillin G and streptomycin, disturbed the regularly implanted pattern of embryos in ICR mice. Our results indicate that symbiotic S. epidermidis plays a role in interaction between embryo and uterus upon implantation in mice.

Breast milk intake facilitates neonatal growth, and its effect is assumed to last long into the adulthood. We recently reported that dietary phosphorus insufficiency reduces the ability of breast milk to promote infant growth in mice. However, how phosphorus confers this ability to milk is still unclear.

Salivary gland hypofunction, also known as xerostomia, occurs as a result of radiotherapy for head and neck cancer, autoimmune diseases, or aging. Xerostomia leads to oral health problems and thus affects the quality of life. Biological salivary gland tissue generated in vitro would provide an alternative mode of treatment for this disease.

Compassionate use, also called expanded access, provides an important pathway for patients with life-threatening conditions to gain access to unapproved investigational drugs, biologics and medical devices. Although the United States (US) and the countries of the Europe Union (EU) have mechanisms that are associated with the use of unapproved products, as of May 2015 there was no such mechanism in Japan. Instead, unapproved products are used under a physician's discretion in conjunction with the Japan Medical Practitioners' Act or Advanced Medical Care B. However, there are some issues and questions to consider under the current circumstances in Japan as follows: (A) it is difficult for the local regulator to monitor the use of unapproved products; (B) there is no information collected on the safety of these products to protect patients; (C) it is difficult to assure the quality of the products; (D) it is difficult for patients to obtain detailed information about unapproved products and their availability; and (E) it is not clear who should cover the cost of the unapproved products. In this paper, we assess the current compassionate use, or expanded access-related mechanisms, of the US, the EU and Japan in regard to drugs, medical devices and biologics, including human cells and tissue products, and discuss the benefits and issues of these mechanisms. The purpose of these mechanisms is principally to save patients with life-threatening condition. However, the information obtained after the compassionate use is potentially useful to facilitate marketing authorization. In fact, the data from compassionate use cases are employed in some approval review reports to indicate the product safety.

Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein involved in the signal transduction pathways. This dataset enlists proteins which interact with Grb2 in the presence and absence of a mitogenic stimulus. Grb2 expressing HEK293 cells were cultured in light and heavy labeled SILAC media. Normal lysine and arginine were incorporated as light labels while 8 and 10 Da heavier labels of respective isotopes were used for heavy labeling. While light labeled cells were used to enrich basal Grb2 interactome, the heavy labeled cells were stimulated in presence of epidermal growth factor (EGF) to investigate the altered Grb2 interactome dynamics. Equal number of EGF stimulated and non-stimulated cells was pooled, lysed and subjected to affinity purification coupled to mass spectrometry (AP-MS). The variety of Grb2 protein partners changed as a consequence of EGF stimulation. Additionally, SILAC labeling helped in quantitative estimation of altered association of a few interactors with the bait protein. Data are available via PRIDE repository with the dataset identifier PXD012957 (https://www.ebi.ac.uk/pride/archive/projects/PXD012957).

Despite considerable research, evidence supporting associations between the 'Retail Food Environment' (RFE) and obesity remains mixed. Differences in the methods used to measure the RFE may explain this heterogeneity. Using data on a large (n = 10,111) sample of adults from the Yorkshire Health Study (UK), we modelled cross-sectional associations between the RFE and weight status using (i) multiple definitions of 'Fast Food', 'Convenience' and 'Supermarkets' and (ii) multiple RFE metrics, identified in a prior systematic review to be common in the literature. Both the choice of outlet definition and the choice of RFE metric substantively impacted observed associations with weight status. Findings differed in relation to statistical significance, effect sizes, and directions of association. This study provides novel evidence that the diversity of RFE measurement methods is contributing to heterogeneous study findings and conflicting policy messages. Greater attention is needed when selecting and communicating RFE measures in research.

Understanding the structural mechanism by which proteins and peptides aggregate is crucial, given the role of fibrillar aggregates in debilitating amyloid diseases and bioinspired materials. Yet, this is a major challenge as the assembly involves multiple heterogeneous and transient intermediates. Here, we analyze the co-aggregation of Aβ40 and Aβ16-22, two widely studied peptide fragments of Aβ42 implicated in Alzheimer's disease. We demonstrate that Aβ16-22 increases the aggregation rate of Aβ40 through a surface-catalyzed secondary nucleation mechanism. Discontinuous molecular dynamics simulations allowed aggregation to be tracked from the initial random coil monomer to the catalysis of nucleation on the fibril surface. Together, the results provide insight into how dynamic interactions between Aβ40 monomers/oligomers on the surface of preformed Aβ16-22 fibrils nucleate Aβ40 amyloid assembly. This new understanding may facilitate development of surfaces designed to enhance or suppress secondary nucleation and hence to control the rates and products of fibril assembly.

A magnetic resonance (MR)-, computed tomography (CT)-, single-photon emission computed tomography (SPECT)-, and positron emission tomography (PET)-compatible carbon-fiber sheet resistor for temperature maintenance in small animals where space limitations prevent the use of circulating fluids was developed. A 250 Ω carbon-fiber sheet resistor was mounted to the underside of an imaging cradle. Alternating current, operating at 99 kHz, and with a power of 1-2 W, was applied to the resistor providing a cradle base temperature of ∼37°C. Temperature control was implemented with a proportional-integral-derivative controller, and temperature maintenance was demonstrated in 4 mice positioned in both MR and PET/SPECT/CT scanners. MR and CT compatibility were also shown, and multimodal MR-CT-PET-SPECT imaging of the mouse abdomen was performed in vivo. Core temperature was maintained at 35.5°C ± 0.2°C. No line-shape, frequency, or image distortions attributable to the current flow through the heater were observed on MR. Upon CT imaging, no heater-related artifacts were observed when carbon-fiber was used. Multimodal imaging was performed and images could be easily coregistered, displayed, analyzed, and presented. Carbon fiber sheet resistors powered with high-frequency alternating current allow homeothermic maintenance that is compatible with multimodal imaging. The heater is small, and it is easy to produce and integrate into multimodal imaging cradles.

With the development of platforms enabling the integration and use of phenome, genome, and exposome data in the context of international research, data management challenges are increasing, and scalable solutions for cross border and cross domain semantic interoperability need to be developed. Reusing routinely collected clinical data, especially, requires computable portable phenotype algorithms running across different electronic health record (EHR) products and healthcare systems. We propose a framework for describing and comparing mediation platforms enabling cross border phenotype identification within federated EHRs. This framework was used to describe the experience gained during the EHR4CR project and the evaluation of the platform developed for accessing semantically equivalent data elements across 11 European participating EHR systems from 5 countries. Developers of semantic interoperability platforms are beginning to address a core set of requirements in order to reach the goal of developing cross border semantic integration of data.

Embedded pragmatic clinical trials (PCTs) are set in routine health care, have broad eligibility criteria, and use routinely collected electronic data. Many consider them a breakthrough innovation in clinical research and a necessary step in clinical trial development. To identify barriers and success factors, we reviewed published embedded PCTs and interviewed 30 researchers and clinical leaders in 7 US delivery systems.

Health systems are challenged by care underutilization, overutilization, disparities, and related harms. One problem is a multiyear latency between discovery of new best practice knowledge and its widespread adoption. Decreasing this latency requires new capabilities to better manage and more rapidly share biomedical knowledge in computable forms. Knowledge objects package machine-executable knowledge resources in a way that easily enables knowledge as a service. To help improve knowledge management and accelerate knowledge sharing, the Knowledge Object Reference Ontology (KORO) defines what knowledge objects are in a formal way.

We aim to describe the anatomy and symmetry patterns of the optic canal in patients having undergone maxillofacial CT imaging.

Background: Some individuals with autism find it challenging to use and understand language in conversation, despite having good abilities in core aspects of language such as grammar and vocabulary. This suggests that pragmatic skills (such as understanding implied meanings in conversation) are separable from core language skills. However, it has been surprisingly difficult to demonstrate this dissociation in the general population. We propose that this may be because prior studies have used tasks in which different aspects of language are confounded. Methods: The present study used novel language tasks and factor analysis to test whether pragmatic understanding of implied meaning, as part of a broader domain involving social understanding, is separable from core language skills. 120 adult participants were recruited online to complete a 7-task battery, including a test assessing comprehension of conversational implicature. Results: In confirmatory analysis of a preregistered model, we compared whether the data showed better fit to a two-factor structure (including a "social understanding" and "core language" factor) or a simpler one-factor structure (comprising a general factor). The two-factor model showed significantly better fit. Conclusions: This study supports the view that interpreting context-dependent conversational meaning is partially distinct from core language skills. This has implications for understanding the pragmatic language impairments reported in autism.

Estrogen decreasing during menopause can create problems in the cardiovascular organs, brain, urogental tract, and bone. Estrogen replacement therapy (ERT) can be used to increase estrogen levels. However, side-effects including breast cancer may limit their use. Tempe and tofu are natural plat-based foods which contain phytoestrogens. The aim of this research was to compare estrogen serum levels in ovariectomized rats given tempe flour and tofu flour. This research was conducted on female rats, aged 12 months (n = 72 rats). Rats were grouped into 5 groups: tempe flour, tofu flour, estradiol, casein and non-ovariectomized. The intervention was carried out for two months with three observation points; i) in the second week, ii) fifth week and iii) eighth week. Estrogen serum analysis was done by ELISA (Estradiol EIA-2693). The mean and the differences between treatment groups were analysed using one way ANOVA with post hoc polynomial contrasts (LSD). The highest estrogen serum in the second week intervention was found in the estradiol group followed by the tempe flour, tofu flour, non-ovariectomized and casein groups, respectively. The tempe flour group had the highest mean serum estrogen levels in the fifth week, followed by the estradiol group, non-ovariectomized group, tofu group and casein group. At the eighth week of intervention, the highest estrogen serum level was found in the tempe flour group followed by the estradiol group, tofu flour group, non ovariectomy group and casein group. Interventions in the fifth and eighth weeks showed significant differences between groups (p < 0.05). It was concluded that tempe flour rendered twice the serum estrogen level compared to tofu flour. Further research is needed in the form of clinical trials to prove that effect in humans.

The aim of this study was to explore the variability in DNA quality and quantity along a gradient of industrial processing of botanical ingredients from raw materials to extracts.

The present work analyses the chromatographic profile of the peels from fruits of different citrus cultivated in Colombia: sweet orange (Citrus sinensis [L.] Osbeck var. Valencia), mandarins (Citrus reticulata L. var. Arrayana and Oneco), Key lime (Citrus aurantifolia [Christ.] Swingle var. Pajarito), Mandarine lime (Citrus x limonia, a hybrid between Citrus reticulata and Citrus x limon) and Tahitian lime (C. latifolia Tanaka, syn. Persian lime). Coumarins, furanocoumarins and polymethoxylated flavones are the major compounds. Then, six coumarins were isolated and identified from fruits of Tahitian and Key lime corresponding to 5-geranyloxy-7-methoxycoumarin; 5,7-dimethoxycoumarin (syn. limettin); 5,8-dimethoxypsoralen (syn. isopimpinellin); 5-methoxypsoralen (syn. bergaptene); 5-geranoxypsoralen (syn. bergamottin) and 5-(2,3-dihydroxy-3-methylbutoxy) psoralen (syn. oxypeucedanin hydrate). Coumarins and furanocoumarins were quantified by liquid chromatography (HPLC-DAD). Results show that the prenylated compounds were present in high concentrations in Tahitian and Key lime but in very low amounts in mandarins and sweet orange. Subsequently, the antifungal activity (inhibition of mycelial growth and germination of spores) of the coumarins against the fungus causing the anthracnose, Colletotrichum sp. (isolated from aerial parts of Tahitian lime) was determined. The compounds limettin and bergaptene, as well as mixtures of them, showed significant inhibitory effect (radial growth and spore germination) when compared to the control. Finally, the effect of some recognized elicitors to induce the coumarin production in fruits of C. latifolia was evaluated. The results showed that the chemical profiles are dependent on the applied elicitor and the post-induction time. As a result of the induction, a high concentration of some coumarins and furanocoumarins was maintained in the course of time for the Tahitian lime. In conclusion, isolated coumarins could be involved in the defense mechanisms of C. latifolia, C. aurantifolia and C. limonia and their accumulation may be modulated by the application of elicitors.

Derepression of transcription factors is the key mechanism for triggering plant jasmonate (JA) responses. Unlike regulating certain physiological functions for the majority of transcription factors in JA signaling, MYC2 and EIN3 control more diverse aspects. MYC2 predominantly participates in wounding response, metabolism, and root growth inhibition, while EIN3 (and its closest homolog EIL1) regulates defense gene expression and root hair development. Recently, it was reported that MYC2 and EIN3/EIL1 proteins mutually interact with each other and suppress their interaction partner's transcriptional activities. To understand their contributions in the modulation of transcriptomic network, we initially identified 1,495 differentially expressed jasmonate (JA)-responsive genes in wild-type Arabidopsis through RNA-seq analysis. Among them, 25% or 4.2% were independently regulated by EIN3/EIL1 or MYC2, respectively. Further analysis showed that EIN3/EIL1 and MYC2 interdependently regulate 16.3% of the JA-regulated transcriptome, including downregulation of three auxin-related genes, which might confer JA-inhibited root elongation. Lastly, we found that <30 genes were antagonistically regulated by MYC2 and EIN3/EIL1. We conclude that EIN3/EIL1 play a dominant role while MYC2 largely relies on EIN3/EIL1 for executing its transcriptional activity, either synergistically or antagonistically.