A Comparison of Lingual Pressure Generation Measures Using Two Devices in Community-Dwelling, Typically Aging Adults: An Important Clinical Implication.

DESIGN: A multisite, prospective, and randomized within-subject design study. SETTING: Five university settings in varied geographical areas in the United States. PURPOSE: The purpose of this study was to compare lingual pressure generation using the Tongueometer (TO) and the Iowa Oral Performance Instrument (IOPI) in typically aging, community-dwelling adults during three measurement tasks: maximum isometric pressure (MIP), regular effort saliva swallow (RESS) pressure, and effortful saliva swallow pressure (ESP). PARTICIPANTS: Eighty-seven typically aging, community-dwelling adults (aged 55 years and over) with no self-reported history of swallowing or neurological disorders were recruited to complete this study. RESULTS: Strong positive associations were found between the lingual pressure generation measures from the TO and IOPI in all tasks in typically aging adults, with Pearson correlations ranging from r = .780 to .874, p < .001. Agreement between the devices (Lin's concordance correlation coefficient) ranged from moderate for the MIP (ρc = .78) and ESP (ρc = .61) tasks to weak agreement for the RESS task (ρc = .47). MIP, RESS pressure, and ESP were lower when measured by the TO compared with the IOPI, p < .001. CONCLUSIONS: The TO measures lingual pressure generation similarly to the IOPI but pressures register lower when using the TO than the IOPI in typically aging persons. This supports the need for developing normative values specific to the TO device or development of a valid and reliable conversion formula from TO to IOPI normative values. At this time, the clinical use of reference values from the TO should not be generalized to IOPI normative values.

Flexibility for Intensity Dosing in Lingual Resistance Exercises: A Large Randomized Clinical Trial in Typically Aging Adults as Proof of Principle.

OBJECTIVE: The objective of this study was to determine the effect of intensity dosing during tongue exercise on tongue pressure generation, adherence, and perceived effort. DESIGN: This was a five-site, prospective, randomized clinical trial. Outcome measures were obtained across multiple baselines, biweekly during exercise, and 4-weeks post-intervention. SETTING: The general community at each study site. PARTICIPANTS: Typically aging adults between 55-82 years of age with no history of neurological or swallowing disorders. Eighty-four volunteers completed the study. INTERVENTIONS: Participants were randomly assigned to one of four exercise groups: (a) maximum intensity/no biofeedback, (b) progressive intensity/no biofeedback, (c) maximum intensity/biofeedback, and (d) progressive intensity/biofeedback. Half of the participants completed a maintenance exercise program. OUTCOME MEASURES: Maximum isometric pressure (MIP), regular effort saliva swallow pressure, adherence, and the Borg Rating of Perceived Exertion Scale. RESULTS: All exercise protocols were efficacious for gains in MIP (large effect sizes; Cohen's d). Group 3 made gains in regular effort saliva swallow pressure (medium effect size). There was a significant change in perceived exertion for regular effort saliva swallow pressure at 8 weeks. Tongue pressure gains were maintained at 1 month, regardless of maintenance group status. Mean adherence across groups was high. CONCLUSIONS: All groups improved pressure generation. Intensity dosing differences did not affect strength gains, adherence, or detraining. Regular effort saliva swallow pressure may be most responsive to maximum intensity with biofeedback. The findings suggest flexibility in approach to tongue exercise protocols. Tongue muscles may differ from limb muscles in terms of dose response and neuroplasticity principles.

A Case of Pseudomembranous Colitis of Unknown Etiology.

Pseudomembranous colitis (PC) is a nonspecific bowel injury resulting from decreased oxygenation, endothelial damage, and impaired blood flow to the mucosa. Although the most well-known cause of PC is Clostridium difficile (C. difficile), several diseases and medications can cause or predispose individuals to PC, such as microscopic colitis, infectious organisms, inflammatory conditions, nonsteroidal anti-inflammatory drugs, and chemotherapy agents. Here, we present the case of a patient who completed treatment for C. difficile infection but developed worsening PC of unknown etiology.

Metabolic Inhibitors of O-GlcNAc Transferase That Act In†Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.

O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT). O-GlcNAc is conserved within mammals and is implicated in a wide range of physiological processes. Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice. These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells. We show that of these inhibitors, 2-deoxy-2-N-hexanamide-5-thio-d-glucopyranoside (5SGlcNHex) acts in vivo to induce dose- and time-dependent decreases in O-GlcNAc levels in various tissues. Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.

Patient Safety Errors: Leveraging Health Information Technology to Facilitate Patient Reporting.

Patient safety continues to be a national challenge not only for providers but for patients and families as well. In an attempt to standardize processes and systems, we have lost opportunities for improvement. For instance, current patient safety reporting systems tend to favor capturing details around events that are classified as highly clinically significant (i.e., sentinel-level and never events); yet little to no effort is spent on capturing information about less evident errors or near misses, nor simply about concerns that are more experiential in nature. As a result, patients' experiences and observations are relegated to the notion of satisfaction, real-time reporting remains illusive, and the ability to learn across incidents remains anecdotal rather than systematic. Herein we propose an alternative, real-time, innovative model that merges syndromic surveillance and patient engagement to embrace patient-initiated reporting of patient safety events and concerns. The result would be a patient safety system where patients are partners, in both the conduct of their care, and in the quality of the healthcare delivered.

The Challenge of Improving Breast Cancer Care Coordination in Safety-net Hospitals: Barriers, Facilitators, and Opportunities.

BACKGROUND: Minority breast cancer patients tend to have higher rates of adjuvant treatment underuse. We implemented a web-based intervention that closes referral loops between surgeons and oncologists at inner-city safety-net hospitals serving high volumes of minority breast cancer patients to assist these hospitals and improve care coordination. RESEARCH DESIGN: Following intervention implementation, we conducted interviews with key personnel to improve our understanding of the implementation process and to identify barriers, facilitators, and opportunities for improvement. We used the constant comparative method of analysis to code interview transcripts and identify common themes regarding intervention implementation. SUBJECTS: We interviewed 64 administrative and clinical key informants from 10 inner-city safety-net hospitals with high volumes of minority breast cancer patients. RESULTS: We found substantial barriers to implementing an intervention designed to support care coordination efforts, despite initial feedback that the intervention itself was both easy to use and in line with organizational goals. We also characterized facilitators and challenges of breast cancer care coordination in the safety-net environment, as well as opportunities to improve intervention design to support increased quality of breast cancer care. CONCLUSIONS: Coordination of care for women with breast cancer is extremely important, but safety-net hospitals face considerable resource constraints from lack of time, support, and information systems. As safety-net hospital networks grow across numerous care sites, the challenge of care coordination will likely increase, highlighting the importance of interventions that can be successfully implemented and used to promote better care.

Post-translational O-GlcNAcylation is essential for nuclear pore integrity and maintenance of the pore selectivity filter.

O-glycosylation of the nuclear pore complex (NPC) by O-linked N-acetylglucosamine (O-GlcNAc) is conserved within metazoans. Many nucleoporins (Nups) comprising the NPC are constitutively O-GlcNAcylated, but the functional role of this modification remains enigmatic. We show that loss of O-GlcNAc, induced by either inhibition of O-GlcNAc transferase (OGT) or deletion of the gene encoding OGT, leads to decreased cellular levels of a number of natively O-GlcNAcylated Nups. Loss of O-GlcNAc enables increased ubiquitination of these Nups and their increased proteasomal degradation. The decreased half-life of these deglycosylated Nups manifests in their gradual loss from the NPC and a downstream malfunction of the nuclear pore selective permeability barrier in both dividing and post-mitotic cells. These findings define a critical role of O-GlcNAc modification of the NPC in maintaining its composition and the function of the selectivity filter. The results implicate NPC glycosylation as a regulator of NPC function and reveal the role of conserved glycosylation of the NPC among metazoans.

Targeting of metallothionein by L-homocysteine: a novel mechanism for disruption of zinc and redox homeostasis.

OBJECTIVE: L-homocysteine and/or L-homocystine interact in vivo with albumin and other extracellular proteins by forming mixed-disulfide conjugates. Because of its extremely rich cysteine content, we hypothesized that metallothionein, a ubiquitous intracellular zinc-chaperone and superoxide anion radical scavenger, reacts with L-homocysteine and that homocysteinylated-metallothionein suffers loss of function. METHODS AND RESULTS: 35S-homocysteinylated-metallothionein was resolved in lysates of cultured human aortic endothelial cells in the absence and presence of reduced glutathione by SDS-PAGE and identified by Western blotting and phosphorimaging. Using zinc-Sepharose chromatography, L-homocysteine was shown to impair the zinc-binding capacity of metallothionein even in the presence of reduced glutathione. L-Homocysteine induced a dose-dependent increase in intracellular free zinc in zinquin-loaded human aortic endothelial cells within 30 minutes, followed by the appearance of early growth response protein-1 within 60 minutes. In addition, intracellular reactive oxygen species dramatically increased 6 hours after L-homocysteine treatment. In vitro studies demonstrated that L-homocysteine is a potent inhibitor of the superoxide anion radical scavenging ability of metallothionein. CONCLUSIONS: These studies provide the first evidence that L-homocysteine targets intracellular metallothionein by forming a mixed-disulfide conjugate and that loss of function occurs after homocysteinylation. The data support a novel mechanism for disruption of zinc and redox homeostasis.