Capture rates of comorbidity measures at inpatient rehabilitation facilities after a stroke or brain injury.

BACKGROUND: Comorbidity indices have been used to represent the overall medical complexity of patient populations in clinical research; however, it is not known how well they capture the comorbidities of patients with a stroke or brain injury admitted to inpatient rehabilitation facilities (IRFs). OBJECTIVE: To determine how well commonly used comorbidity indices capture the comorbidities of patients admitted to IRFs after a stroke or brain injury. DESIGN: Cross-sectional, retrospective study. SETTING: IRFs nationwide. PARTICIPANTS: Adults from four impairment groups: (1) hemorrhagic stroke, (2) ischemic stroke, (3) nontraumatic brain injury (NTBI), and (4) traumatic brain injury (TBI). MAIN OUTCOME MEASURES: International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were extracted from the Uniform Data System for Medical Rehabilitation (UDSMR) for IRF discharges from October 1, 2015 to December 31, 2017. The percentage of discharges captured by Deyo-Charlson, Elixhauser, and Centers for Medicare and Medicaid Services (CMS) tiers was determined, as was the percentage of comorbidities captured. These measures were also compared with respect to their ability to capture chronic medical complexity by examining the percentage of codes captured after removal of codes deemed to represent hospital complications or sequela of the admission diagnosis. RESULTS: The percentage of discharges without at least one ICD-10-CM code captured by any index ranged from 0.3%-3.8%. The percentage of comorbidities with a prevalence exceeding 1% captured by at least one index ranged from 37.1%-43.6%. Chronic comorbidities were most likely to be captured by Elixhauser (40.7%-44.4%), followed by Deyo-Charlson (7.8%-9.6%), then CMS tiers (4.5%-6.9%). Existing comorbidity measures capture most IRF discharges related to a brain injury or stroke, whereas most medical comorbidities escape representation. Several common, functionally relevant diagnoses were not captured. CONCLUSION: The use of comorbidity indices in the IRF neurologic injury population should account for the fact that these measures miss several common, important comorbidities.

A gel-free Ti3C2Tx-based electrode array for high-density, high-resolution surface electromyography.

Wearable sensors for surface electromyography (EMG) are composed of single- to few-channel large-area contacts, which exhibit high interfacial impedance and require conductive gels or adhesives to record high-fidelity signals. These devices are also limited in their ability to record activation across large muscle groups due to poor spatial coverage. To address these challenges, we have developed a novel high-density EMG array based on titanium carbide (Ti3C2Tx) MXene encapsulated in parylene-C. Ti3C2Tx is a two-dimensional nanomaterial with excellent electrical, electrochemical, and mechanical properties, which forms colloidally stable aqueous dispersions, enabling safe, scalable solutions-processing. Leveraging the excellent combination of metallic conductivity, high pseudocapacitance, and ease of processability of Ti3C2Tx MXene, we demonstrate the fabrication of gel-free, high-density EMG arrays which are ~8 µm thick, feature 16 recording channels, and are highly skin-conformable. The impedance of Ti3C2Tx electrodes in contact with human skin is 100-1000x lower than the impedance of commercially-available electrodes which require conductive gels to be effective. Furthermore, our arrays can record high-fidelity, low-noise EMG, and can resolve muscle activation with improved spatiotemporal resolution and sensitivity compared to conventional gelled electrodes. Overall, our results establish Ti3C2Tx-based bioelectronic interfaces as a powerful platform technology for high-resolution, non-invasive wearable sensing technologies.

Geriatric rehabilitation.

Rehabilitation of elderly persons is accompanied by unique challenges, as the physiologic changes with aging may be compounded by a multitude of psychologic, social, and genetic factors. In this chapter we present an overview of the impairments that develop with aging. We discuss factors to consider when evaluating a patient with functional complaints and opportunities for treatment. We provide an overview of common injuries encountered in the elderly, prognostication, and general strategies employed for rehabilitation. New treatment options and areas of ongoing research are also discussed.

Average proportional consecutive interval difference accurately differentiates spontaneous activity from motor unit potentials.

INTRODUCTION: An objective method is required to detect spontaneous activity (SA) for prevalence studies in needle electromyography (EMG). Because of frequent similarities in the morphology of SA and motor unit potentials (MUP), identification of SA depends on assessment of firing regularity, which has not yet been quantitated through a modern interface. METHODS: Prospective recordings obtained from patients referred for electrodiagnostic evaluation were analyzed by using decomposition-based quantitative EMG (DQEMG) customized to calculate descriptive statistics. RESULTS: Forty-four MUP recordings (39 participants) and 80 SA recordings (62 participants) were analyzed. One hundred one of 124 recordings successfully interfaced with DQEMG. The remaining recordings were analyzed in Audacity. Average proportional consecutive interval differences differentiated SA from MUPs with 97.5% sensitivity (confidence interval [CI] 91.3%-99.7%) and 100.0% specificity (CI 92%-100%). There was substantial overlap, however, for SD and mean consecutive differences. DISCUSSION: Average proportional consecutive interval difference accurately differentiates SA from MUPs and may be useful in future prevalence studies of SA.

Evaluation of cell binding activities of Leptospira ECM adhesins.

Pathogenic spirochetes of the genus Leptospira are the causative agents of leptospirosis, a zoonotic infection that occurs globally. The bacteria colonize the renal proximal tubules of many animals and are shed in the urine. Contact with the urine, or with water contaminated with the urine of infected animals can cause infection of new host animals, including humans. Mechanisms of colonization of the proximal tubule and other tissues are not known, but specific interactions between bacterial adhesins and host substrates are likely to be critical in this process. Several extracellular matrix (ECM) adhesins have been previously identified, but more recently, it has been shown that Leptospira bind more efficiently to cells than ECM. In this work, recombinant forms of five putative Leptospira ECM adhesins, namely LipL32, Loa22, OmpL1, p31/LipL45, and LenA were evaluated for binding to cells as well as an expanded variety of ECM components. Reproducible and significant adhesin activity was demonstrated only for OmpL1, which bound to both mammalian cell lines tested and to glycosaminoglycans (GAGs). While determination of biologically significant bacterial adhesion activity will require generation of site-directed mutant strains, our results suggest that OmpL1 is a strong candidate for future evaluation regarding the roles of the adhesin activity of the protein during L. interrogans infection.

PPAR gamma, bioactive lipids, and cancer progression.

In this article we review the evolution of cancer research involving PPARgamma, including mechanisms, target genes, and clinical applications. For the last thirteen years, the effects of PPARgamma activity on tumor biology have been studied intensely. Most of this research has focused upon the potential for employing agonists of this nuclear receptor in cancer treatment. As a monotherapy such agonists have shown little success in clinical trials, while they have shown promise as components of combination treatments both in culture and in animal models. Other investigations have explored a possible role for PPARgamma as a tumor suppressor, and as an inducer of differentiation of cancer stem cells. Whereas early studies have yielded variable conclusions regarding the prevalence of PPARgamma mutations in cancer, the protein level of this receptor has been more recently identified as a significant prognostic marker. We predict that indicators of PPARgamma activity may also serve as predictive markers for tailoring treatments.

G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer.

GPR43 is a G-protein-coupled receptor for short-chain fatty acids (SCFAs). Expression of GPR43 is detected in hematopoietic tissues and the large intestine. SCFAs are derived from bacterial fermentation and metabolism of undigested dietary fibers and have been recognized for their cancer prevention activities in the colon. The role of SCFAs, particularly butyrate, in colon cancer therapy has been extensively studied, and its tumor suppressive functions are believed to be due to their intracellular actions, notably inhibition of histone deacetylase. In our study, we show that SCFAs also exert their antitumor effects via receptor GPR43 and that GPR43 is frequently lost in colon cancer cells. Immunohistostaining revealed that GPR43 immunoreactivity was high in normal colon tissues (N = 31) but was markedly reduced or completely lost in most colorectal adenocarcinoma tissues (N = 70) and their corresponding lymph node metastatic adenocarcinomas (N = 38). RT-PCR analysis detected the presence of full length GPR43 mRNA in only one (HT-29) of nine established human colon cancer cell lines. Restoration of GPR43 expression in HCT8 human colonic adenocarcinoma cells induced G0/G1 cell cycle arrest and activated caspases, leading to increased apoptotic cell death after propionate/butyrate treatment. Restored GPR43 expression, coupled with propionate treatment, induced an upregulation of p21 and a decrease in the levels of cyclin D3 and cyclin-dependent kinases (CDKs) 1 and 2, while the CDK4 and CDK6 levels remained unchanged. Our results suggest that GPR43 functions as a tumor suppressor by mediating SCFA-induced cell proliferation inhibition and apoptotic cell death in colon cancer.

Camptothecin attenuates cytochrome P450 3A4 induction by blocking the activation of human pregnane X receptor.

Differential regulation of drug-metabolizing enzymes (DMEs) is a common cause of adverse drug effects in cancer therapy. Due to the extremely important role of cytochrome P450 3A4 (CYP3A4) in drug metabolism and the dominant regulation of human pregnane X receptor (hPXR) on CYP3A4, finding inhibitors for hPXR could provide a unique tool to control drug efficacies in cancer therapy. Camptothecin (CPT) was demonstrated as a novel and potent inhibitor (IC(50) = 0.58 microM) of an hPXR-mediated transcriptional regulation on CYP3A4 in this study. In contrast, one of its analogs, irinotecan (CPT-11), was found to be an hPXR agonist in the same tests. CPT disrupted the interaction of hPXR with steroid receptor coactivator-1 but had effects on neither the competition of ligand binding nor the formation of the hPXR and retinoid X receptor alpha heterodimer, nor the interaction between the regulatory complex and DNA-responsive elements. CPT treatment resulted in delayed metabolism of nifedipine in human hepatocytes treated with rifampicin, suggesting a potential prevention of drug-drug interactions between CYP3A4 inducers and CYP3A4-metabolized drugs. Because CPT is the leading compound of topoisomerase I inhibitors, which comprise a quickly developing class of anticancer agents, the findings indicate the potential of a new class of compounds to modify hPXR activity as agonists/inhibitors and are important in the development of CPT analogs.