Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro.

Equine recurrent uveitis (ERU) is an immune-mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T-cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuclear cells were isolated. The markers CD21, CD3, CD4, and CD8 were used to identify lymphocyte subsets while CD25, CD62L, Foxp3, IFNγ, and IL10 were used to identify T-cell phenotype. Adipose-derived MSCs were expanded, irradiated (to control proliferation), and incubated with CD4+ T-cells from healthy horses, after which lymphocytes were collected and analyzed via flow cytometry. The percentages of T-cells and B-cells in horses with ERU were similar to normal horses. However, CD4+ T-cells from horses with ERU expressed higher amounts of IFNγ indicating a pro-inflammatory Th1 phenotype. When co-incubated with MSCs, activated CD4+ T-cells reduced expression of CD25, CD62L, Foxp3, and IFNγ. MSCs had a lesser ability to decrease activation when cell-cell contact or prostaglandin signaling was blocked. MSCs continue to show promise as a treatment for ERU as they decreased the CD4+ T-cell activation phenotype through a combination of cell-cell contact and prostaglandin signaling

Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection

A multicenter experience using adipose-derived mesenchymal stem cell therapy for cats with chronic, non-responsive gingivostomatitis.

BackgroundThe ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus.MethodsTo meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA.ResultsWe found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8lo cells in blood prior to and at 3 months post-ASC therapy. CD8lo cells may serve as a potential "predictor" for response to systemic ASC therapy.ConclusionFresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases

Measurement And Modeling Of Short Copper Cables For Ultra-wideband Communication

High-speed communication using the copper network, originally installed for telephony, is one of the dominant Internet access techniques. Several variants of a technology referred to as digital subscriber line (DSL) have been developed, standardized and installed during the last two decades. Essentially, DSL achieves high rates by exploiting wide bands of the copper cable channel. The shorter the cable, the wider the band that can be used efficiently for communication. Current DSL standards foresee the use of bands up to 30MHz. Cable properties have been studied by means of measurements, characterization and modeling up to frequencies of 30MHz. Recent investigations have shown that it is feasible both from technical and from economical point of view to exploit very short cables (up to 200m) even further and use bands above 30MHz. A prerequisite for further evaluation and the design of such ultra-wideband copper (UWBC) systems is the extension of existing cable models to higher frequencies. This paper presents wideband measurement results of insertion loss and crosstalk coupling in a 10-pair cable of various length values for frequencies up to 200MHz. We compare the results with extrapolations of cable models that are established in the 30MHz-range.6390Chen, W.Y., (1998) DSL: Simulation Techniques and Standards Development for Digital Subscriber Line Systems, , Macmillan Technical Publishing, ISBN 1-57870-017-5G.selt: Updated issues list for G.selt (2004) ITU-T Temporary Document SS U09, , ITU-TAsymmetric digital subscriber line (ADSL) transceivers (1999) ITU Recommendation G.992.1, , ITU-T, JuneAsymmetric digital subscriber line (ADSL) transceivers (1999) ITU Recommendation G.992.2, , ITU-T, JuneAsymmetric digital subscriber line (ADSL) extended bandwidth (ADSL2+) (2005) ITU Recommendation G.992.5, , ITU-TStarr, T., Cioffi, J.M., Silverman, P., (1998) Understanding Digital Subscriber Line Technology, , Prentice Hall, Englewood CliffsDedieu, H., The copper channel - Loop charactersitics and models (2005) Fundamentals of DSL Technology, , ch. ISBN 0849319137, AUERBACHVan Der Brink, R.F.M., (1998) Cable Reference Models for Simulating Metallic Access Networks, , Permanent Document TM6(97), ETSI STC TM6, Luleå, Sweden, JunePaul, C.R., (1994) Analysis of Multiconductor Transmission Lines, , Wiley, ISBN 0-471-02080-XCook, J.W., (1996) Parametric Modelling of Twisted Pair Cables for VDSL, , Temporary Document TD22, ETSI STC TM6, Vienna, Austria, MarVan Der Brink, R.F.M., (1997) Measurements and Models on Dutch Cables, , Temporary Document TD15, ETSI STC TM6, Tel Aviv, Israel, MarPollakowski, M., (1996) DTAG Cables Transmission Characteristics, , Temporary Document TD40, ETSI STC TM6, Vienna, Austria, MarPythoud, F., (1998) Model of Swiss Access Network Cables, , Temporary Document TD48, ETSI STC TM6, Madrid, Spain, JanHeylen, L., Musson, J., (1999) Cable Models Predict Physically Impossible Behavior in Time Domain, , Temporary Document TD08, ETSI STC TM6, Amsterdam, Netherlands, NovMusson, J., (1998) Maximum Likelihood Estimation of the Primary Parameters of Twisted Pair Cables, , Temporary Document TD06, ETSI STC TM6, Madrid, Spain, SeptBoets, P., Zekri, M., Van Biesen, L., Bostoen, T., Pollet, T., On the identification of cables for metallic access networks (2001) 18th IEEE Instrumentation and Measurement Technology Conference IMTC2001, 2, pp. 1348-1353. , Budapest, Hungary, MayBostoen, T., Boets, P., Zekri, M., Van Biesen, L., Pollet, T., Rabijns, D., Estimation of the transfer function of the access network by means of one-port scattering parameter measurements at the central office (2002) IEEE Journal on Selected Areas in Communication, 20, pp. 936-948. , JuneVery-high-bit-rate Digital Subscriber Line (VDSL) metallic interface part 1: Functional requirement and common specification (2001) T1E1.4/2000-009R3, , ANSI T1E1.4, FebVan Der Brink, R.F.M., (2001) Laboratory Performance Tests for XDSL Systems, , Permanent Document TM6(98)10, ETSI STC TM6, Sophia Antipolis, France, FebValenti, C., NEXT and FEXT models for twisted-pair North American loop plant (2002) IEEE Journal on Selected Areas in Communication, 20, pp. 893-900. , JuneNedev, N.H., McLaughlin, S., Cook, J.W., Wideband UTP cable measurements and modelling for MIMO systems (2004) Proc. European Signal Processing Conf. EUSIPCO 2004, , (Vienna, Austria), SeptMagesacher, T., Henkel, W., Tauböck, G., Nordström, T., Cable measurements supporting xDSL technologies (2002) Journal E&i Elektrotechnik und Informationstechnik, 199, pp. 37-43. , FebMagesacher, T., Ödling, P., Börjesson, P.O., Henkel, W., Nordström, T., Zukunft, R., Haar, S., On the capacity of the copper cable channel using the common mode (2002) Proc. IEEE Global Telecommun. Conf. GLOBECOM 2002, , (Taipei, Taiwan), NovTomita, N., Ohmura, M., Low-frequency crosstalk loss characteristics of balanced cables (1989) Electron. Commun. Japan, Part 1, 72 (3), pp. 95-105Goedbloed, J.J., Aspects of EMC at the equipment level (1997) Proc. 12th Intl. Symp. Electromagn. Compat., pp. 23-38. , (Zurich, Switzerland), FebWerner, J.J., The HDSL environment (1991) IEEE Journal on Selected Areas in Communication, 9, pp. 785-800. , AugConte, R.A., A crosstalk model for balanced digital transmission in multipair cables (1986) AT&T Tech. J., 65, pp. 41-59. , May-JunSchutt-Aine, J.E., High-frequency characterization of twisted-pair cables (2001) IEEE Trans. on Commun., 49, pp. 598-601. , AprGresh, P.A., Physical and transmission characteristics of customer loop plant (1969) The Bell System Technical Journal, 48, pp. 3337-3385. , DecManhire, L.M., Physical and transmission characteristics of customer loop plant (1978) The Bell System Technical Journal, 57, pp. 35-39. , JanPierce, S.B., Crosstalk in twisted pair circuits (1986) Proc. Intl. Wire and Cable Symp., pp. 349-354Fung, A., Lee, L.S., Falconer, D.D., A facility for near end crosstalk measurements on ISDN subscriber loops (1989) Proc. IEEE Global Telecommun. Conf, , paper 54.

Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.

Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full-thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c) normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel-treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic-preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase-2 expression at week 1. Histologically, significantly more MSC-treated wounds were categorized as pro-healing than pro-inflammatory. Wound area was significantly affected by treatment: MSC-injected wounds were consistently smaller than gel-treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. Stem Cells Translational Medicine 2018;7:98-108

Calcium supplementation and risk of dementia in women with cerebrovascular disease

OBJECTIVE: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up. METHODS: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70–92 years. At baseline in 2000–2001, and at follow-up in 2005–2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria. RESULTS: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01–4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54–12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36–33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28–6.96, p = 0.011), but not in groups without these conditions. CONCLUSIONS: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed

Observation of Umklapp processes in non-crystalline materials

Umklapp processes are known to exist in cristalline materials, where they control important properties such as thermal conductivity, heat capacity and electrical conductivity. In this work we report the provocative observation of Umklapp processes in a non-periodical system, namely liquid Lithium. The lack of a well defined periodicity seems then not to prevent the existence of these scattering processes mechanisms provided that the local order of the systems i.e. the maxima of the static structure factor supply the equivalent of a reciprocal lattice vector in the case of cristalline materials.Comment: 13 pages P