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Agrin is an extracellular matrix protein involved in the formation of the postsynaptic apparatus of the neuromuscular junction. In addition to spinal motor neurons, agrin is expressed by many other neuronal populations throughout the nervous system. Agrin's role outside of the neuromuscular junction, however, is poorly understood. Here we use the polymerase chain reaction to examine expression and alternative splicing of agrin in mouse somatosensory cortex during early postnatal development in vivo and in dissociated cell culture. Peak levels of agrin gene expression in developing cortex coincide with ingrowth of thalamic afferent fibres and formation of thalamocortical and intracortical synapses. Analysis of alternatively spliced agrin messenger RNA variants shows that greater than 95% of all agrin in developing and adult somatosensory cortex originates in neurons, including isoforms that have little or no activity in acetylcholine receptor aggregation assays. The levels of expression of "active" and "inactive" isoforms, however, are regulated during development. A similar pattern of agrin gene expression is also observed during a period when new synapses are being formed between somatosensory neurons growing in dissociated cell culture. Changes in agrin gene expression, observed both in vivo and in vitro, are consistent with a role for agrin in synapse formation in the central nervous system.

Background: Many hospitals have implemented early rapid response teams to improve detection of patients at risk for decline. However, formal evaluation of these programs is rare., Objective: To evaluate the Early Nurse Intervention Team program at a large community hospital in the southeastern United States., Methods: A retrospective evaluation was performed of unplanned intensive care unit transfers, hospital length of stay, length of stay index, ventilator days, and mortality in 2 patient groups: those with and those without an Early Nurse Intervention Team nurse present., Results: There was a marked decline in unplanned intensive care unit transfers as the Early Nurse Intervention Team nurse staffing increased. There were no significant interaction or main effects for length of stay, length of stay index, ventilator days, or mortality between the 2 groups., Conclusions: This study showed a positive impact of implementation of an Early Nurse Intervention Team program, with significant savings given the cost of unplanned intensive care unit transfers., (©2022 American Association of Critical-Care Nurses.)

Accurate and timely transmission of medical records between skilled nursing facilities and acute care settings has been logistically problematic. Often people are sent to the hospital with a packet of paper records, which is easily misplaced. The COVID-19 pandemic has further magnified this problem by the possibility of viral transmission via fomites. To protect themselves, staff and providers were donning personal protective equipment to review paper records, which was time-consuming and wasteful. We describe an innovative process developed by a team of hospital leadership, members of a local collaborative of skilled nursing facilities, and leadership of this collaborative group, to address this problem. Many possible solutions were suggested and reviewed. We describe the reasons for selecting our final document transfer process and how it was implemented. The critical success factors are also delineated. Other health systems and collaborative groups of skilled nursing facilities may benefit from implementing similar processes., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Unplanned hospital readmissions represent a significant health care value problem with high costs and poor quality of care. A significant percentage of readmissions could be prevented if clinical inpatient teams were better able to predict which patients were at higher risk for readmission. Many of the current clinical decision support models that predict readmissions are not configured to integrate closely with the electronic health record or alert providers in real-time prior to discharge about a patient's risk for readmission. We report on the implementation and monitoring of the Epic electronic health record-"Unplanned readmission model version 1"-over 2 years from 1/1/2018-12/31/2019. For patients discharged during this time, the predictive capability to discern high risk discharges was reflected in an AUC/C-statistic at our three hospitals of 0.716-0.760 for all patients and 0.676-0.695 for general medicine patients. The model had a positive predictive value ranging from 0.217-0.248 for all patients. We also present our methods in monitoring the model over time for trend changes, as well as common readmissions reduction strategies triggered by the score.

Food and feed safety assessment is not enhanced by performing protein expression analysis on stacked trait products. The expression levels of six proteins in cotton matrices from four single cotton events and three conventionally stacked trait cotton products are reported. Three proteins were for insect control; two proteins confer herbicide tolerance; and one protein was a transformation-selectable marker. The cotton matrices were produced at three U.S., five Brazil, and two Argentina field trials. Similar protein expression was observed for all six proteins in the stacked trait products and the single events. However, when two copies of the bar gene were present in the stacked trait products, the expression level of phosphinothricin acetyl transferase herbicide tolerance was additive. Conventional breeding of genetically engineered traits does not alter the level or pattern of expression of the newly introduced proteins, except when multiple copies of the same transgene are present.

Objectives: This study aimed to determine if abdominal sacral colpopexy (ASC) using mesh can be safely combined with sigmoid resection and anastomosis., Methods: This is a single institution, retrospective chart review of patients who underwent combined ASC and suture rectopexy with sigmoid resection between January 1, 2007, and December 31, 2011. Charts were screened for outcome data and complications related to the placement of synthetic mesh at the time of bowel resection to include readmission and reoperation rates, infection, bowel obstruction, fistula, and mesh erosion. Outcome data for patients receiving combined procedures were compared to 2 separate cohorts of patients as follows: a group that underwent only ASC with polypropylene mesh and a group that underwent only sigmoid resection plus or minus suture rectopexy. The DINDO surgical classification system was used for each cohort to further analyze complications., Results: There were 133 patients in the ASC only group (ASC only), 34 in the combined ASC and sigmoid resection group (Combined), and 27 in the sigmoidectomy plus rectopexy group (Colorectal only). The Colorectal only cohort had a higher rate of postoperative ileus; ASC only 3.8%, Combined 5.9%, Colorectal 22.2% (P = 0.004). There were otherwise no differences in intraoperative and postoperative complications or in the DINDO classification scores., Conclusions: Abdominal sacral colpopexy with placement of synthetic mesh at the time of sigmoid resection and anastomosis does not seem to increase the rate of intraoperative or postoperative complications.

Application of energy in minimally invasive hysterectomy creates thermal injury which may increase vaginal cuff dehiscence. The purpose of this study was to compare vaginal tissue damage in a swine model between the two power settings of ultrasonic energy. This was an IACUC-approved, prospective, single-blinded study analyzing energy-induced damage to the swine vagina during robotic hysterectomy. Multiple colpotomy transections were performed on 18 animals using robotic ultrasonic energy, the exact same platform used in human surgery. Specimens (n = 72) were analyzed by a veterinary pathologist blinded to the energy source. Thermal injury was microscopically measured. Mean thermal injury (µm) was not statistically different between Max-Setting 5 and Min-Setting 3 (1243 ± 544 vs. 1293 ± 554; 95 % CI -310 to 210, p = 0.66). Time (s) to complete transection was significantly shorter when using Setting 5 (13.00 ± 7.75 vs. 17.92 ± 9.03; 95 % CI -4.92 to -8.88, p = 0.001). The rate of injury (µm/s) for Setting 5 also trended toward being higher (118.98 ± 72.81 vs. 93.03 ± 62.34; 95 % CI -5.91 to 57.81, p = 0.053). In these swine vaginal specimens, energy-induced tissue damage was not statistically different for the two ultrasonic power settings. Max-Setting 5 was faster and trended toward a higher rate of damage; this was balanced by equivalent distance of tissue injury compared with Min-Setting 3. In larger human specimens, the use of Max-Setting 5 may be recommended to decrease surgical time as it is faster and causes an equivalent amount of injury to Min-Setting 3.

Study Objective: To determine whether patients receiving perioperative glycopyrrolate during midurethral sling surgery had more acute but temporary postoperative urinary retention., Design: Retrospective cohort from 2006 to 2011., Setting: Northern Virginia community urology practice., Measurements: To minimize variability in surgical technique and postoperative care, all cases were from a single fellowship-trained urologist who performed most of the female incontinence procedures. Inclusion criteria were charts of women, 18 years of age or older, who had a primary preoperative diagnosis of stress urinary incontinence (SUI) and who underwent a midurethral sling procedure. Of 151 patients charts, 135 met study eligibility: 57 (42.2%) patients received glycopyrrolate; 78 (57.8%) did not. The postoperative course of those who did and did not receive glycopyrrolate was compared and formed the basis of group allocation. Data collected included age, body mass index, incontinence type, smoking status, diabetes mellitus, surgery performed, anesthesia type, estimated blood loss, intraoperative fluids, surgery end time to void, and postoperative urinary retention., Main Results: No differences existed between the groups in baseline or surgical data. Seven patients (5.2%) had acute temporary postoperative retention, two of whom received glycopyrrolate and 5 did not (3.51% vs 6.41%; relative risk [RR] 0.55, 95% CI 0.11 -2.72, P = 0.70). Excluding those with continued persistent voiding dysfunction beyond 48 hours from surgery, only 3 patients (2.22%) had acute temporary postoperative urinary retention: one received glycopyrrolate and two did not (1.75% vs 2.56%; RR 0.68, 95% CI 0.064 - 7.36; P = 0.99)., Conclusion: Acute temporary postoperative urinary retention is rare after midurethral slings. Glycopyrrolate during anesthesia induction does not appear significantly to increase this rate., (© 2013.)

PURPOSE. The purposes of this study were to investigate the frequency of MET activation in uveal melanomas (UMs), to study the potential molecular mechanism for its activation, and to assess the utility of MET inhibition as a potential therapy for UM. METHODS. The frequency of MET activation in UMs was studied by using immunohistochemistry and Western blot analysis in 46 primary UMs and six UM cell lines. Sequencing was used for detection of activating mutations in the MET gene, and the effect of selective MET inhibition was assessed by cell proliferation and migration assays. RESULTS. The results showed that the majority (82.5%) of the 46 UMs expressed activated MET protein. Three of the UM cell lines, C918, 92.1, and MEL202, showed strong MET and pMET expression, whereas the other three showed weaker expression. Sequence analysis identified no activating mutations in MET in any of the 22 tumors or in the six UM cell lines. Selective MET blocking showed inhibition of tumor cell proliferation at an IC(50) ranging from 2.5 to 5.2 microM. A significant inhibition of UM cell migration was also observed starting at 1.25 microM. CONCLUSIONS. The results indicate that MET is activated in a significant number of UMs and also that MET activation in UMs is most likely through indirect gene activation rather than copy number alteration or mutation involving the MET gene. MET inhibition could be a target of therapy for UM.

Cytochrome P450 (CYP) enzymes are important in the metabolism of some endogenous compounds, environmental and dietary xenobiotics and many drugs. Many of these enzymes have genetic polymorphisms that produce significant changes in metabolic activity, however the function of other polymorphisms is unknown. Genetic polymorphisms have important influences on variability in human pharmacokinetics, including intra-individual differences in drug toxicity, drug interactions and response to chemotherapy. Other factors that influence drug metabolism include differences in enzyme expression due to differences in age, gender, smoking status, exposure to dietary or environmental xenobiotics or co-administration of other drugs. In addition, some xenobiotics and drugs can directly inhibit or induce the activity of CYPs. All of these factors can produce differences in metabolic capacities among individuals which can produce toxicity in some patients and sub-effective dosing in others. Maximum clinical benefit will require a more complete understanding of the influence of these polymorphisms on allele function and their interaction with inducers and inhibitors of enzyme expression or activity. This effort will permit the pharmacogenetic screening of patients before the administration of drugs and result in the identification of individuals who are prone to adverse reactions or poor response, resulting in more effective individualized therapy.

To better understand the interactions of the pathways of activation and detoxification on the metabolism of the putative carcinogen, PhIP, we administered a dose of 70-84 microg [2-14C] PhIP (17.5 [microCi 14C) 48-72 h before scheduled colon surgery. Blood and urine collected for the next 48-72 h was evaluated by linear accelerator mass spectroscopy (AMS) and scintillation counting LC-MS to identify specific PhIP metabolites. The thermostable phenol sulfotransferase (SULT1A1) phenotype was correlated with the 4'-PhIP-SO4 levels in the urine at 0-4 h (R = 0.86, P = 0.059). The CYP1A2 activity had a negative correlation with PhIP serum levels at 1 h (R = 0.94, P = 0.06) and a positive correlation with urine N-OH-PhIP levels at 0-4 h (R = 0.85, P = 0.15). This low level radioisotope method of determining the influence of phenotype on metabolism will significantly improve our understanding of the interrelationships of these pathways and provide a critical foundation for the development of individual risk assessment.

Maturation of electrical excitability during early postnatal development is critical to formation of functional neural circuitry in the mammalian neocortex. Little is known, however, about the changes in gene expression underlying the development of firing properties that characterize different classes of cortical neurons. Here we describe the development of cortical neurons with two distinct firing phenotypes, regular-spiking (RS) and fast-spiking (FS), that appear to emerge from a population of immature multiple-spiking (IMS) neurons during the first two postnatal weeks, both in vivo (within layer IV) and in vitro. We report the expression of a slowly inactivating, 4-AP-sensitive potassium current (K4-AP) at significantly higher density in FS compared with RS neurons. The same current is expressed at intermediate levels in IMS neurons. The kinetic, voltage-dependent, and pharmacological properties of the K4-AP current are similar to those observed by heterologous expression of Kv3.1 potassium channel mRNA. Single-cell RT-PCR analysis demonstrates that PCR products representing Kv3.1 transcripts are amplified more frequently from FS than RS neurons, with an intermediate frequency of Kv3.1 detection in neurons with immature firing properties. Taken together, these data suggest that the Kv3.1 gene encodes the K4-AP current and that expression of this gene is regulated in a cell-specific manner during development. Analysis of the effects of 4-AP on firing properties suggests that the K4-AP current is important for rapid action potential repolarization, fast after-hyperpolarization, brief refractory period, and high firing frequency characteristic of FS GABAergic interneurons.

Published estimates of the number of primary auditory afferents in the rat differ by as much as 30%. We undertook to determine if the widely varying estimates were related to methodological differences, especially the difference between counting cells in Rosenthal's canal and fibers in the cochlear nerve. Type I ganglion cells and myelinated cochlear nerve fibers in the same ears were counted in Long-Evans and Sprague-Dawley strains. Type II spiral ganglion cells were also counted. In each strain the numbers of myelinated fibers and type I ganglion cells were essentially the same. Means for the Long-Evans were 18,036 fibers and 17,749 cells. Means for Sprague-Dawleys were higher: 19,444 fibers and 19,229 cells. The mean number of type II ganglion cells was also greater in Sprague-Dawley than in Long-Evans rats: 1,388 and 1,170, respectively. Cell and fiber counts from the two ears of the same animal differed on average by only 1%. The number of auditory afferents did not change with age over the range (2-10 months) studied here. Several methodological differences have probably contributed to the varying estimates of type I primary auditory afferents, but the discrepancies are not inherent in counts of fibers and spiral ganglion cells.

The metabolic activation of food-borne heterocyclic amines to colon carcinogens in humans is hypothesized to occur via N-oxidation followed by O-acetylation to form the N-acetoxy arylamine that binds to DNA to give carcinogen-DNA adducts. These steps are catalyzed by hepatic cytochrome P4501A2 (CYP1A2) and acetyltransferase-2 (NAT-2), respectively, which are known to be polymorphic in humans. On the basis of this proposed metabolic activation pathway, patients at greatest risk to develop colorectal cancer or nonfamilial polyps should be those who possess both the rapid NAT-2 and rapid CYP1A2 phenotypes and are exposed to high dietary levels of carcinogenic heterocyclic amines. Using a method that involves caffeine administration and high pressure liquid chromatographic analysis of urinary metabolites, we have determined the CYP1A2 and NAT-2 phenotypes of 205 controls and 75 cancer/polyp cases. Exposure information was obtained using a dietary and health habits questionnaire. Both the rapid CYP1A2 and rapid NAT2 phenotypes were each slightly more prevalent in cases versus controls (57% and 52% versus 41% and 45%, respectively). However, the combined rapid CYP1A2-rapid NAT-2 phenotype was found in 35% of cases and only 16% of the controls, giving an odds ratio of 2.79 (P = 0.002). Univariate analysis of the questionnaire indicated that age, rapid-rapid phenotype, and consumption of well done red meat were associated with increased risk of colorectal neoplasia. Furthermore, a logistic regression model that included age (as a continuous variable), consumption of well done red meat, and rapid-rapid phenotype as independent covariates gave odds ratios of 1.08, 2.08, and 2.91, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Understanding the pathophysiology of the boutonniere deformity requires a complete understanding of the anatomy of the dorsal tendon apparatus. This unique tendon mechanism often becomes unbalanced, requiring correction of its components. Splinting is the cornerstone of treatment for the boutonniere deformity. In the acute stage, splinting ensures that the continuity of the central tendon to its insertion into the middle phalanx is maintained, and in the chronic stage, its function is to correct the flexion contracture of the PIP joint and stretch the retinacular ligaments. Splinting is also important postoperatively because it permits healing of the central tendon and lateral bands in their correct anatomic positions. Without proper splinting, the patient with the boutonniere deformity could not be successfully treated. Frequently, surgery is necessary, and the choice of procedure depends on the stage of the condition and the extent of the defect in the extensor tendon mechanism. The procedure also depends on the success of the splinting program and stretching of the tight retinacular structures. If passive joint mobility can be restored and if tendon imbalance and retinacular tightness persist, rebalancing is necessary. This rebalancing can be accomplished by a tenotomy of the terminal extensor tendon, a lysis or release of the retinacular structures, or release of the insertion of the extensor tendon at the base of the proximal phalanx. Reconstituting the defect in the central tendon over the PIP joint is accomplished by using a variety of procedures, including mobilization and advancement of the more proximal portion of the central tendon, shifting the lateral bands, or a tendon graft.

Transverse divisions of the mid-shaft of freshly frozen pig metacarpals were fixed with Kirschner wires of two sizes and using four different configurations. Compared to the usual cross-pin fixation using wires of 0.889 mm. four wires (0.712 mm) eccentrically placed and with their ends hooked provided a 300% improvement in bending rigidity and 170% in bending movement.

Nine types of internal fixation techniques were tested in 4-point bending using a pig metacarpal model for phalangeal fractures. Levels of bending rigidity and bending moments at failure were determined, and the modes of failure are described. Plate and screw fixation afforded the greatest rigidity, and epiphyseal fractures occurred, leaving intact the test section. Flexible wire loop fixation failed by wire cutting into bone when a square knot was used. Twisted wire unraveled when placed in tension. Depending on the fracture type and the wire placement. Kirschner wires failed either by slipping in the bone, twisting in the bone cortex, or bending at the bone cortex interface. Rigidity varied widely depending on the way in which the wires were employed.

The effects of concurrent disopyramide phosphate and quinidine sulfate therapy were studied in 16 normal healthy adults. No adverse effects serious enough to warrant discontinuation of therapy were observed. There was a small but significant increase in disopyramide serum concentration when concurrent quinidine therapy was given and a small decrease in quinidine serum concentration when disopyramide was added. No significant change in elimination half-life was seen for either drug. Both drugs produced prolongation of the corrected QT interval. This QT prolongation was greater for quinidine than for disopyramide.

In treating skin loss of the hand, the surgeon must be aware of the placement of skin and scars, the unique quality of palmar skin, the tendency of skin grafts to hyperpigment, the need for pain-free and well-padded amputation stumps that are free of painful neuromata and poorly padded phalangeal remnants. Skin grafts, palmar skin loss, regional flaps, distant flaps and local flaps are discussed. The histology and function characteristics of normal skin of the hand are reviewed.

Fingertip injuries and lacerations of the hand are often dismissed as inconsequential, although this attitude can lead to more serious problems. Appropriate and timely treatment of these injuries prevents loss of function, preserves digital sensibility, and lessens the need for reconstructive surgery.