Trekking Poles to Aid Multiple Sclerosis Walking Impairment: An Exploratory Comparison of the Effects of Assistive Devices on Psychosocial Impact and Walking.

Background: Walking dysfunction is reported by two-thirds of persons with multiple sclerosis (MS). Assistive devices are frequently recommended to improve walking; however, it is uncommon to consider their psychosocial impact, although many users abandon their assistive devices. The psychosocial impact, walking, balance, and fatigue associated with three assistive devices were compared to guide clinical decision making.

Efficacy of Vortioxetine Monotherapy for Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial.

Purpose/background: There are few efficacious pharmacological treatments for posttraumatic stress disorder (PTSD) and many patients fail to benefit from existing treatments. Vortioxetine, a recently developed antidepressant, acts as a serotonin modulator through inhibition of the serotonin transporter and actions at multiple types of serotonin receptors. Its unique pharmacodynamic profile suggests it may have efficacy for the treatment of PTSD.

Lifetime employment in schizophrenia: correlates of developing long term unemployment after being employed before.

Background: Challenges in employment are highly prevalent among people with schizophrenia regardless of their employment history. Although supportive employment can be effective, few participants sustain meaningful competitive employment. Our goal was to identify the correlates of developing sustained unemployment.

The evolutionary origins and diversity of the neuromuscular system of paired appendages in batoids.

Appendage patterning and evolution have been active areas of inquiry for the past two centuries. While most work has centred on the skeleton, particularly that of amniotes, the evolutionary origins and molecular underpinnings of the neuromuscular diversity of fish appendages have remained enigmatic. The fundamental pattern of segmentation in amniotes, for example, is that all muscle precursors and spinal nerves enter either the paired appendages or body wall at the same spinal level.

Macrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells.

Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix (ECM) fragmentation and inflammation. However, the mechanisms by which these events are coupled thereby fueling focal vascular damage are undefined. Here we report through single-cell RNA-sequencing of diseased aorta that the neuronal guidance cue netrin-1 can act at the interface of macrophage-driven injury and ECM degradation.

Platelet-Derived MRP-14 Induces Monocyte Activation in Patients With Symptomatic Peripheral Artery Disease.

Background: Peripheral artery disease (PAD), a diffuse manifestation of atherothrombosis, is a major cardiovascular threat. Although platelets are primary mediators of atherothrombosis, their role in the pathogenesis of PAD remains unclear.

Objectives: The authors sought to investigate the role of platelets in a cohort of symptomatic PAD.

Effect of a rapid clinical protocol to the conversion from central venous hemodialysis catheter to arteriovenous access.

Purpose: Evaluation of the rapid conversion protocol that includes an ambulatory dialysis access center (DAC), and a three-step clinical pathway, to the conversion rate from central venous hemodialysis (HD) catheter to functioning arteriovenous (AV) access.

Methods: Prospective data were collected on 97 consecutive catheter-dependent HD patients. DAC is defined as an ambulatory unit, able to accommodate clinic visits, ultrasound examinations, surgical, interventional and hybrid procedures.

Reducing audio stimulus presentation latencies across studies, laboratories, and hardware and operating system configurations.

Using differing computer platforms and audio output devices to deliver audio stimuli often introduces (1) substantial variability across labs and (2) variable time between the intended and actual sound delivery (the sound onset latency). Fast, accurate audio onset latencies are particularly important when audio stimuli need to be delivered precisely as part of studies that depend on accurate timing (e.g.

The effect of repeated freezing and thawing on human sperm DNA fragmentation.

Objective: To investigate the effects of repeated freezing and thawing on human sperm motility, vitality, and DNA integrity.

Design: A prospective clinical study.

Setting: Tertiary care fertility clinic.

The DNA integrity of cryopreserved spermatozoa separated for use in assisted reproductive technology is unaffected by the type of cryoprotectant used but is related to the DNA integrity of the fresh separated preparation.

Objective: To investigate and compare seven different commercially available cryoprotectant media in terms of the DNA integrity of spermatozoa recovered after cryopreservation and separation using density gradient centrifugation (DGC).

Design: A prospective clinical study.

Setting: Tertiary care fertility clinic.

Role of CTLA-4, IL-18 and IL-10 on the Induction of Low Dose Oral Tolerance.

Oral Tolerance is the temporary loss of systemic immunological responsiveness to a specific soluble antigen after ingestion of that antigen. Results from our lab and others indicated that CTLA-4 and lack of IL-12 played a role in the induction of low dose oral tolerance at the Th1 cell level. Previous literature suggested that IL-18 also played a role in preventing oral tolerance induction while the cytokine IL-10 had been shown to be a factor contributing to suppressed immune responses.

Effect of in vivo administration of anti-CTLA-4 monoclonal antibody and IL-12 on the induction of low-dose oral tolerance.

Oral tolerance has been characterized as an immunological hyporesponsiveness to fed antigen. Previous studies have suggested that high-dose oral tolerance involves the preferential interaction of B7 with CTLA-4 on the T cell. To determine whether similar mechanisms are involved in the induction of low-dose oral tolerance, mice were treated with anti-CTLA-4 monoclonal antibody (MoAb), with or without IL-12, at the time of feeding.

Abrogation of oral tolerance by feeding encapsulated antigen.

Results from previous studies have indicated that suppression of immune responses cannot be abrogated once oral tolerance has been established. Using a new methodology, OVA was encapsulated and fed to tolerized BDF1 mice. Results from these studies indicated that although IgG2a titers remained low, total IgG and IgG1 antibody titers were no longer suppressed compared to controls.

Induction of oral tolerance in TGF-beta 1 null mice.

Previous studies have suggested that oral tolerance induction by low doses of Ag is mediated by inhibitory cytokines, particularly TGF-beta 1. To examine the roles of TGF-beta 1 and other inhibitory cytokines in the induction of oral tolerance, TGF-beta 1 null mice and controls were gavaged with 10 to 20 mg (high dose) or 1 mg (low dose) of OVA for 3 days. After immunization with OVA, the in vitro proliferative response of OVA-specific popliteal lymph node cells was assessed.

Activation patterns of murine B cells after oral administration of an encapsulated soluble antigen.

Oral administration of soluble protein antigen, ovalbumin (OVA), encapsulated by an acid-resistant acrylic polymer, induced a strong immune response in BDF1 mice. Mice fed the encapsulated OVA showed activation of antigen-specific IgA, IgG and IgG1 isotype antibody-secreting cells which migrated to various lymphoid tissues via the common mucosal immune system traffic pathway. The highest number of antigen-specific antibody secreting cells was found in the Peyer's patches isolated from the upper segment of the small intestine, with their numbers declining along the length of the intestinal tract.

Activation patterns of murine T cells after oral administration of an enterocoated soluble antigen.

An orally administered soluble protein antigen, ovalbumin (OVA), enterocoated with an acid-resistant acrylic polymer, induced a strong humoral immune response in BDF1 mice, exhibiting Th2 cell phenotype, typified by increased OVA-specific IgA, IgG1, and IgE antibody responses. This antibody response was accompanied by OVA-specific T cell proliferation response and IL-4 cytokine production. Mice fed enterocoated OVA and administered anti-IL-4 mAb showed a shift of the immune response toward the Th1 cell phenotype as evidenced by increased IFN-gamma production and anti-OVA IgG2a isotype antibody response.

Activation patterns of murine B cells after oral administration of an encapsulated soluble antigen.

Oral administration of soluble protein antigen, ovalbumin (OVA), encapsulated by an acid-resistant acrylic polymer, induced a strong immune response in BDF1 mice. Mice fed the encapsulated OVA showed activation of antigen-specific IgA, IgG and IgG1 isotype antibody-secreting cells which migrated to various lymphoid tissues via the common mucosal immune system traffic pathway. The highest number of antigen-specific antibody secreting cells was found in the Peyer's patches isolated from the upper segment of the small intestine, with their numbers declining along the length of the intestinal tract.

Effector functions of antibody and CD8+ cells in resolution of rotavirus infection and protection against reinfection in mice.

The importance of antibody and CD8+ cells in resolution of murine rotavirus (EDIM) infection and protection against reinfection was examined with two strains of B-cell-deficient mice. Following inoculation of one strain (JHD), rotavirus infection was resolved within days, but when later reinoculated with EDIM, these mice again shed rotavirus. Thus, effector mechanisms other than antibody resolved viral shedding in JHD mice but were insufficient to prevent reinfection.

A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding.

P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like glycoprotein expressed on the surface of myeloid cells and serves as the high affinity counterreceptor for P-selectin. The PSGL-1-P-selectin interaction is calcium dependent and requires presentation of sialyl-Lewisx (sLex)-type structures on the O-linked glycans of PSGL-1. We report here the identification of a non-carbohydrate component of the binding determinant that is critical for high affinity binding to P-selectin.

Effect of in vivo depletion of CD4+ and CD8+ cells on the induction and maintenance of oral tolerance.

The role of CD8+ and CD4+ cells in the generation and maintenance of high-dose oral tolerance has been investigated. Mice depleted of CD8+ cells prior to or subsequent to oral tolerization with OVA continued to express suppressed humoral and/or T cell proliferative responses to the homologous antigen. To assess the effect of CD4+ cell depletion on oral tolerance, mice were depleted of CD4+ cells prior to or subsequent to oral tolerization with OVA.

Leukocyte recruitment into human skin transplanted onto severe combined immunodeficient mice induced by TNF-alpha is dependent on E-selectin.

In order to study the in vivo role of E-selectin in human inflammation, we have developed a model in which human skin is transplanted onto severe combined immunodeficient (SCID) mice. The grafted skin closely resembles normal skin and retains its human vasculature. After intradermal injection of rTNF-alpha, human E-selectin was rapidly up-regulated on dermal microvessels, with significant expression (determined immunohistochemically) at 1 h postinjection and maximum expression at 2 h postinjection.

Expression cloning of a functional glycoprotein ligand for P-selectin.

The initial adhesive interactions between circulating leukocytes and endothelia are mediated, in part, by P-selectin. We now report the expression cloning of a functional ligand for P-selectin from an HL-60 cDNA library. The predicted amino acid sequence reveals a novel mucin-like transmembrane protein.

Characterization and mechanisms of thymic atrophy in protein-malnourished mice: role of corticosterone.

The purpose of this project was to characterize changes in murine T lymphocyte subpopulations during thymic atrophy induced by protein malnutrition and to determine the role of elevated serum corticosterone in this process. A suitable animal model was generated by placing mice on protein-sufficient (PS) and protein-deficient (PD) diets for 6 weeks. Body weight was monitored to determine the establishment and maintenance of malnutrition.

Spectrum of sialylated and nonsialylated fuco-oligosaccharides bound by the endothelial-leukocyte adhesion molecule E-selectin. Dependence of the carbohydrate binding activity on E-selectin density.

Carbohydrate recognition by the human endothelial-leukocyte adhesion molecule, E-selectin, has been investigated by binding studies using 3H-labeled Chinese hamster ovary cells expressing different levels of the transfected full-length adhesion molecule and a series of structurally defined oligosaccharides linked to the lipid phosphatidylethanolamine dipalmitoate (neoglycolipids) and synthetic glycolipids chromatographed on silica gel plates or immobilized on plastic wells. Evidence is presented for density-dependent binding of the membrane-associated E-selectin not only to 3'-sialyl-lacto-N-fucopentaose II (3'-S-LNFP-II) and 3'-sialyl-lacto-N-fucopentaose III (3'-S-LNFP-III) which express the sialyl Le(a) and sialyl Le(x) antigens, respectively, but also to the nonsialylated analogue LNFP-II; there is a threshold density of E-selectin required for binding to these sialylated sequences, and binding to the nonsialylated analogue is a property only of cells with the highest density of E-selectin expression. The presence of fucose linked to subterminal rather than to an internal N-acetylglucosamine is shown to be a requirement for E-selectin binding, and although the presence of sialic acid 3-linked to the terminal galactose of the LNFP-II or LNFP-III sequences substantially enhances E-selectin binding, the presence of 6-linked sialic acid abolishes binding.

Protein engineering of novel plasminogen activators with increased thrombolytic potency in rabbits relative to activase.

Human tissue-type plasminogen activator (t-PA) is a glycoprotein used currently in thrombolytic therapy for patients with acute myocardial infarction. Due to its rapid rate of clearance from the circulation, continuous intravenous administration of approximately 100 mg over 3 h is recommended. We have previously characterized novel thrombolytic variant forms of t-PA which offer the potential of administration by bolus injection and reduced dosage due to their slower rates of clearance, relative to t-PA.