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Background and Purpose: Poststroke delirium (PSD) is an independent predictor of unfavorable outcome. Despite its individual and socioeconomic burden, its frequency, clinical course, and routine detection remain unresolved. This study aimed to assess psychometric properties of established delirium screening tools and investigate the natural course of PSD., Methods: This study investigated patients presenting with high-risk transient ischemic attacks or ischemic stroke within 24 hours during a 3-month period. Twice-daily screenings for PSD were done using the confusion assessment method, nursing delirium scale, and rapid delirium assessment, and evaluated for noninferiority against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. We investigated demographic and stroke characteristics as predictors of PSD, neurological deficits as predictors of false screening results, and conducted a simulation study to estimate the best timing to identify PSD., Results: We enrolled 141 patients (73.8±10.4 years of age, 61 female) with a mean National Institutes of Health Stroke Scale score of 6.4±6.5. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based PSD incidence was 39%, which manifested within 24 hours in 25% and 72 hours in almost all cases. The confusion assessment method was the only screening tool noninferior to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ratings providing a sensitivity of 82% and specificity of 80%. Age (odds ratio, 1.07 [1.02-1.13] per year, P =0.004) and National Institutes of Health Stroke Scale (odds ratio, 1.24 [1.15-1.34] per point, P <0.001) were predictors of PSD. False-positive screening results were associated with stroke-induced disorientation (odds ratio, 6.1 [3.2-11.61], P <0.001) and neglect (odds ratio, 2.17 [1.22-3.87], P =0.008). Simulations revealed that one in 4 cases is missed with less than daily screenings., Conclusions: PSD is a common complication of stroke and transient ischemic attack. Detection is challenged by confounding effects such as focal neurological deficits and the necessity for at least daily screenings. Future studies are required to investigate implementation of these findings in clinical routine. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03930719.

Objective: Early therapy of sepsis involving fluid resuscitation and antibiotic administration has been shown to improve patient outcomes. A proactive tool to identify patients at risk for developing sepsis may decrease time to interventions and improve patient outcomes. The objective of this study was to evaluate whether the implementation of an automated sepsis screening and alert system facilitated early appropriate interventions., Design: Prospective, observational, pilot study., Setting: Six medicine wards in Barnes-Jewish Hospital, a 1250-bed academic medical center., Patients: Patients identified by the sepsis screen while admitted to a medicine ward were included in the study. A total of 300 consecutive patients were identified comprising the nonintervention group (n=200) and the intervention group (n=100)., Interventions: A real-time sepsis alert was implemented for the intervention group, which notified the charge nurse on the patient's hospital ward by text page., Measurements and Main Results: Within 12 hrs of the sepsis alert, interventions by the treating physicians were assessed, including new or escalated antibiotics, intravenous fluid administration, oxygen therapy, vasopressors, and diagnostic tests. After exclusion of patients without commitment to aggressive management, 181 patients in the nonintervention group and 89 patients in the intervention group were analyzed. Within 12 hrs of the sepsis alert, 70.8% of patients in the intervention group had received≥1 intervention vs. 55.8% in the nonintervention group (p=.018). Antibiotic escalation, intravenous fluid administration, oxygen therapy, and diagnostic tests were all increased in the intervention group. This was a single-center, institution- and patient-specific algorithm., Conclusions: The sepsis alert developed at Barnes-Jewish Hospital was shown to increase early therapeutic and diagnostic interventions among nonintensive care unit patients at risk for sepsis.

Hyperreflectoric rhinitis is related to an unspecific hyperreactivity probably caused by chemical irritants. As a major modulatory role may be attributed to the mucosal innervation, the present study was carried out to examine possible changes in the nasal mucosa innervation. Immunohistochemistry for the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide tyrosine (NPY) revealed abundant staining of nerve fibers. Neuropeptide-contents in mucosal nerves was then quantitatively assessed and significant increases were found for SP (3.00 +/- 0.37 vs. 1.64 +/- 0.34 control group staining intensity) and VIP (2.33 +/- 0.42 vs. 0.82 +/- 0.33). In conclusion, these findings demonstrated differences in human nasal mucosa innervation between nonrhinitic and hyperreflectoric rhinitic subjects and provide evidence for a modulatory participation of neuropeptide-specific subpopulations of nerve fibers in hyperreflectoric rhinitis.

Titin is a giant vertebrate striated muscle protein with critical importance for myofibril elasticity and structural integrity. We show here that the complete sequence of the human titin gene contains 363 exons, which together code for 38 138 residues (4200 kDa). In its central I-band region, 47 novel PEVK exons were found, which contribute to titin's extensible spring properties. Additionally, 3 unique I-band titin exons were identified (named novex-1 to -3). Novex-3 functions as an alternative titin C-terminus. The novex-3 titin isoform is approximately 700 kDa in size and spans from Z1-Z2 (titin's N-terminus) to novex-3 (C-terminal exon). Novex-3 titin specifically interacts with obscurin, a 721-kDa myofibrillar protein composed of 57 Ig/FN3 domains, followed by one IQ, SH3, DH, and a PH domain at its C-terminus. The obscurin domains Ig48/Ig49 bind to novex-3 titin and target to the Z-line region when expressed as a GFP fusion protein in live cardiac myocytes. Immunoelectron microscopy detected the C-terminal Ig48/Ig49 obscurin epitope near the Z-line edge. The distance from the Z-line varied with sarcomere length, suggesting that the novex-3 titin/obscurin complex forms an elastic Z-disc to I-band linking system. This system could link together calcium-dependent, SH3-, and GTPase-regulated signaling pathways in close proximity to the Z-disc, a structure increasingly implicated in the restructuring of sarcomeres during cardiomyopathies.

Titins are megadalton-sized filamentous polypeptides of vertebrate striated muscle. The I-band region of titin underlies the myofibrillar passive tension response to stretch. Here, we show how titins with highly diverse I-band structures and elastic properties are expressed from a single gene. The differentially expressed tandem-Ig, PEVK, and N2B spring elements of titin are coded by 158 exons, which are contained within a 106-kb genomic segment and are all subject to tissue-specific skipping events. In ventricular heart muscle, exons 101 kb apart are joined, leading to the exclusion of 155 exons and the expression of a 2.97-MDa cardiac titin N2B isoform. The atria of mammalian hearts also express larger titins by the exclusion of 90 to 100 exons (cardiac N2BA titin with 3.3 MDa). In the soleus and psoas skeletal muscles, different exon-skipping pathways produce titin transcripts that code for 3.7- and 3.35-MDa titin isoforms, respectively. Mechanical and structural studies indicate that the exon-skipping pathways modulate the fractional extensions of the tandem Ig and PEVK segments, thereby influencing myofibrillar elasticity. Within the mammalian heart, expression of different levels of N2B and N2BA titins likely contributes to the elastic diversity of atrial and ventricular myofibrils.

Background: The killer cell immunoglobulin-like receptors (KIR) are a family of receptors expressed on natural killer (NK) cells and some T cells. Class I HLA molecules on target cells are the ligands for the KIR receptors. The number of KIR genes has been reported to vary between individuals, resulting in different KIR haplotypes. There is little published data on the frequency of each KIR gene and the linkage disequilibrium between the genes. Because there is evidence that NK cells may be involved in bone marrow transplant rejection, we have determined the KIR gene frequencies and possible haplotypic arrangements by linkage disequilibrium analysis in an Australian population., Methods: Controls, patients with leukemia, and unrelated bone marrow donor-recipient pairs were typed for the presence of 11 KIR genes by polymerase chain reaction-sequence specific priming., Results: Ninety percent of the population was found to have a sufficient number and variety of KIR genes to detect any mismatch of HLA-A, -B, and -C alleles on NK target cells. The 11 KIR genes could be divided into two groups based on linkage disequilibrium between pairs of genes. Evidence for a recombination within the KIR gene complex is presented., Conclusion: Typing for the presence of particular KIR genes may be indicated for bone marrow donor-recipient pairs for whom a class I HLA mismatch is unavoidable.

Objectives: To develop an animal model to study transmucosal lentivirus transmission, and to determine whether topical application of contraceptive jelly can block transmission by an infected cell incoulum., Design: Feline immunodeficiency virus (FIV), a lentivirus similar to HIV, causes an AIDS-like disease in domestic cats. HIV is transmitted primarily across mucosal surfaces, and infected cells may be important in this transmission. We tested the ability of FIV-infected cells to transmit infection across the vaginal, rectal and oral mucosa of the cat, and whether a vaginal contraceptive jelly could prevent such transmission., Methods: An inoculum consisting of 2 million FIV-infected primary cat T cells was administered vaginally, rectally or orally to female cats that had received either no pretreatment or pretreatment with a contraceptive jelly containing the detergent nonoxynol-9 as spermicide. Transmission was detected by monitoring recipient animals for viral antibodies and by viral cultures of blood leukocytes., Results: A single dose of the infected cell inoculum efficiently transmitted FIV infection when delivered into the vagina or rectum (10 out of 11 animals became infected). Pretreatment of the vagina (five animals) or rectum (four animals) with contraceptive jelly protected all animals from transmission by the highly infectious inoculum., Conclusions: The cat/FIV model provides an efficient means to study transmucosal transmission of lentivirus infections, and for assessing vaginal barrier methods that could block transmission. One such method, nonoxynol-9 contraceptive jelly, effectively prevents transmucosal transmission by an FIV-infected cell inoculum.