Oklahoma State University Medical Center

BACKGROUND: Changes in employment conditions in the global economy over the past 30 years have led to increased job insecurity and other work organization hazards. These hazards may play a role in creating and sustaining occupational health disparities by socioeconomic position, gender, race, ethnicity, and immigration status. METHODS: A conceptual model was developed to guide the review of 103 relevant articles or chapters on the role of work organization and occupational health disparities identified through a comprehensive search conducted by NIOSH. A second review was conducted of employment and workplace policies and programs designed to reduce the health and safety risks due to job insecurity and other work organization hazards. RESULTS: There is consistent evidence that workers in lower socioeconomic or social class positions are exposed to greater job insecurity and other work organization hazards than workers in higher socioeconomic positions. Likewise, racial and ethnic minorities and immigrants are exposed to greater job insecurity. Limited research examining the effects of interventions targeting work organization hazards on disparities has been conducted; nonetheless, intervention strategies are available and evidence suggests they are effective. CONCLUSIONS: Job insecurity and work organization hazards play a role in creating and sustaining occupational health disparities. Employment and workplace policies and programs have the potential to reduce these hazards, and to reduce disparities.

This study examines the decision of people (N = 56) living in retirement communities to quit driving, and the role of their physician and family in making this decision. Most of the elderly stopped driving when a threshold was reached after an accumulation of compensatory behaviors. Few stopped because of their doctor's advice, although all felt a physician was in the best position to evaluate driving, and family involvement received limited support.

OBJECTIVE: To describe possible correlations between incidence of postpartum depression and the following patient characteristics: age, breastfeeding status, tobacco use, marital status, history of depression, and method of delivery. STUDY DESIGN: Data gathered at routine 4-week postnatal visits were obtained from the patient records of 209 women who gave birth between June 1, 2001, and June 1, 2003, at three university medical clinics in Tulsa, Okla. Inclusion criteria required that the records of potential study subjects contain data on the characteristics noted as well as patient-completed Edinburgh Postnatal Depression Scale forms. RESULTS: Formula feeding in place of breastfeeding, a history of depression, and cigarette smoking were all significant risk factors for an Edinburgh Postnatal Depression Scale score of 13 or higher, indicating probable postpartum depression. CONCLUSION: The authors' findings corroborate the results of previous investigators. To facilitate prophylactic patient education and intervention strategies, a larger study is recommended to determine risk factors for postpartum depression.

Adhesive receptors of the integrin family are primarily involved in cell-extracellular matrix adhesion. Additionally, integrins trigger multiple signaling pathways that are involved in cell migration, proliferation, survival, and differentiation. We previously demonstrated that the activation of integrins containing the beta(1) subunit leads to a selective increase in potassium currents carried by the human ether-a-go-go-related gene (hERG) channels in neuroblastoma and leukemia cells; this current activation modulates adhesion-dependent differentiation in these cells. We hypothesized that the cross-talk between integrins and hERG channels could be traced back to the assembly of a macromolecular signaling complex comprising the two proteins. We tested this hypothesis in both SH-SY5Y neuroblastoma cells and in human embryonic kidney 293 cells stably transfected with hERG1 and, therefore, expressing only the full-length hERG1 protein on the plasma membrane. The beta(1) integrin and hERG1 coprecipitate in these cells and colocalize in both intracellular and surface membrane compartments. The two proteins also coprecipitate with caveolin-1, suggesting the localization of the complex in lipid rafts/caveolae. hERG1-transfected cells undergo an activation of hERG currents after beta(1) integrin-mediated adhesion to fibronectin; concomitant with this activation, the focal adhesion kinase associates with the hERG1 protein and becomes tyrosine phosphorylated. Using hERG1-specific inhibitors, we show that the tyrosine phosphorylation of focal adhesion kinase is strictly dependent on hERG channel activity. Similarly, the activity of the small GTPase Rac1 turned out to be dependent on hERG currents. On the whole, these data indicate that the hERG1 protein associates with beta(1) integrins and modulates adhesion receptor signaling.

PURPOSE: Growth disturbance of the distal femur is the most common complication after distal femoral growth plate fracture. The purpose of our study was to pool data from the literature to determine the incidence of growth disturbance in relation to the Salter-Harris (SH) classification. Additionally, we evaluated the potential influence of fracture displacement and treatment method. METHODS: A structured PubMed search was performed to identify all reports on distal femoral growth plate fractures published in the English language literature, from 1950 to 2007. Reference lists from identified articles and bibliographies from standard pediatric fracture texts were also scrutinized. For a study to be included in this review, it needed to have at least 10 patients with a minimum of 1 year follow-up and be published in the English language. A total of 16 articles met the criteria for inclusion, which accounted for 564 fractures. RESULTS: Of the 564 fractures, 291 (52%) had a growth disturbance. Growth disturbance occurred in 36% of SH 1 fractures, 58% in SH 2, 49% in SH 3, and 64% in SH 4 fractures. In studies with patient-level data, there was growth disturbance in 65% of fractures with displacement and 31% of the fractures with no displacement had growth disturbance. The odds of a displaced fracture having growth arrest was 4 times greater than that of a nondisplaced fracture having a growth arrest. (P = 0.0015) In the studies with patient-level data, 58% (70/121) of fractures treated without fixation developed a growth disturbance, with 37% (45/121) being a clinically significant disturbance. Of the patients treated with fixation, including those who were initially treated without but lost reduction, 63% (19/30) developed a growth disturbance, with 27% (8/30) being clinically significant. Significant growth disturbance was defined as a leg length discrepancy equal to or greater than 1.5 cm and/or 5 degrees of varus or valgus deformity. SH 4 fractures had the greatest incidence of developing a leg length discrepancy greater than 1.5 cm (9/37). Twenty-two percent (112/506) of all distal femoral growth plate fractures developed a leg length discrepancy of greater than 1.5 cm. CONCLUSION AND SIGNIFICANCE: Fifty-two percent of distal femoral growth plate fractures had some form of growth disturbance. Twenty-two percent (112/506) of all distal femoral growth plate fractures developed a leg length discrepancy of greater than 1.5 cm. SH 1 fractures had the lowest incidence of growth disturbance (36%), whereas SH 4 fractures had the highest rate of growth disturbance at 64%. Although there is a greater incidence of growth disturbance in patients who were treated with fixation (58% versus 63%), there was a decreased incidence of significant growth disturbance (37% versus 27%).

The cost to an institution of medication-related problems (MRPs) was studied. A retrospective chart review covering the period from July 1992 through June 1994 was performed for patients at a university-affiliated medical center hospital who were known to have had clinical consequences from an adverse drug reaction (ADR) or medication error. All interventions resulting directly from the problem were recorded. A detailed list of patient charges was reviewed for each patient, and specific charges for the MRP-associated interventions were tabulated. The clinical outcomes used to evaluate intervention costs were categorized as extra laboratory tests, noninvasive procedures, additional treatments, invasive monitoring or procedures, increased length of stay, and intensive care. The cost of each intervention was calculated by applying the cost-to-charge ratio used in the institution's patient-charge-based accounting system. A total of 109 patient charts were reviewed. A total of 349 clinical outcomes associated with MRPs, or an average of 3 outcomes per patient, were detected. The mean +/- S.E. cost of MRP-associated clinical outcomes to the institution ranged from $95 +/- 11 for additional laboratory tests to $2640 +/- 596 for intensive care. The next most costly outcomes were increased length of stay and invasive monitoring or procedures. For the 1911 MRPs reported in 1994, the estimated total cost was almost $1.5 million. A review of the medical records of patients for whom an ADR or medication error had been recorded showed a high cost of these events to the institution, with the cost varying with clinical outcome, and a correspondingly strong opportunity for pharmacists to intervene to save money and improve the quality of care.

The migratory pathway of Naegleria fowleri from the nasal submucosa to the central nervous system (CNS) during the early stage of primary amebic meningoencephalitis (PAM) was investigated in mice. Twenty-one-day-old CD-1 mice were inoculated by intranasal instillation of 1 x 10(6) amebas. Animals were divided into 3 groups of 5 and, after being anesthetized, were killed at intervals of 24, 32, and 48 hr postinoculation by transcardial perfusion with formaldehyde, acetic acid, and methanol. The heads were decalcified, divided in the midsagittal plane, and the area of the cribriform plate removed and embedded in paraffin. Serial sections were cut at 8 microm and stained with a combination of celestin blue, Harris' hematoxylin, and acid fuchsin for light microscopy. Focal inflammation and amebas were observed in the submucosal nerve plexus, olfactory nerves penetrating the cribriform plate, and the olfactory bulb of the brain as early as 24 hr postinoculation. The time periods selected assured that the disease process would not obliterate soft tissue structures. Earlier studies used moribund mice in which the inflammation and the number of amebas were overwhelming. The present study provides convincing evidence that amebas gain initial access to the CNS through olfactory nerves within the cribriform plate during the early stages of PAM.

OBJECTIVE: To examine the association between the degree of healthcare provider continuity and healthcare utilization and costs. STUDY DESIGN: A longitudinal, prospective, observational study. PATIENTS AND METHODS: Data on patients with arthritis, asthma, epigastric pain/peptic ulcer disease, hypertension, and otitis media were collected at each of 6 health maintenance organizations (HMOs). Outcome variables included the number of prescriptions for the target disease and the cost, total number of prescriptions and the cost, the number of outpatient visits, and the number of hospital admissions. Disease-specific severity of illness, type of visit, and provider information were obtained at each encounter. HMO profit status, visit copay, gatekeeper strictness, formulary limitations, use of multisource (generic) drugs, gender, number of months in the study, age, and severity of illness were controlled in the analyses. RESULTS: There were 12,997 patients followed for more than 99,000 outpatient visits, 1000 hospitalizations, and more than 240,000 prescriptions. Increasing the number of primary or specialty care providers a patient encountered during the study generally was associated with increased utilization and costs when HMO and patient characteristics were controlled. The number of specialty care providers also increased as the number of primary care providers increased. The incremental increase in pharmacy costs per patient per year with each additional provider ranged between $19 in subjects with otitis media to $58 in subjects with hypertension. CONCLUSIONS: Continuity of care was associated with a reduction in resource utilization and costs. As healthcare delivery systems are designed, care continuity should be promoted.

Approximately 30% to 50% of women that have the diagnosis of endometriosis also struggle with infertility. Twenty five percent to 50% of women diagnosed with infertility also have endometriosis, but the endometriosis may not be severe enough to be the primary etiology of infertility. White women have been reported to be more likely than African American women to have endometriosis. In addition, risk factors for endometriosis include below average body mass index, smoking, and alcohol use. Below is a discussion regarding the various ways in which endometriosis decreases fecundity and also discusses potential outcomes of fertility treatments regarding endometriosis.

Cyclin dependent kinase (CDK) inhibitors, such as flavopiridol, demonstrate significant single-agent activity in chronic lymphocytic leukemia (CLL), but the mechanism of action in these nonproliferating cells is unclear. Here we demonstrate that CLL cells undergo autophagy after treatment with therapeutic agents, including fludarabine, CAL-101, and flavopiridol as well as the endoplasmic reticulum (ER) stress-inducing agent thapsigargin. The addition of chloroquine or siRNA against autophagy components enhanced the cytotoxic effects of flavopiridol and thapsigargin, but not the other agents. Similar to thapsigargin, flavopiridol robustly induces a distinct pattern of ER stress in CLL cells that contributes to cell death through IRE1-mediated activation of ASK1 and possibly downstream caspases. Both autophagy and ER stress were documented in tumor cells from CLL patients receiving flavopiridol. Thus, CLL cells undergo autophagy after multiple stimuli, including therapeutic agents, but only with ER stress mediators and CDK inhibitors is autophagy a mechanism of resistance to cell death. These findings collectively demonstrate, for the first time, a novel mechanism of action (ER stress) and drug resistance (autophagy) for CDK inhibitors, such as flavopiridol in CLL, and provide avenues for new therapeutic combination approaches in this disease.

Quantitative receptor autoradiography was used to assess mu, delta and kappa opioid binding sites in the lumbar spinal cord of rats with neuropathic pain due to a unilateral chronic constriction injury (CCI) of the sciatic nerve. Sections from spinal segment L4 were obtained from animals of treatment groups (left side CCI, right side sham-operated) at 2, 5 and 10 days post surgery and from control animals (left side sham-operated, right side untreated) 10 days post surgery. Autoradiograms were made of the equilibrium binding of the highly selective opioid radioligands, 3H-sufentanil (mu ligand), 3H-[d-Pen2,5]-enkephalin (DPDPE, delta ligand) and 3H-U69593 (Upjohn compound, kappa ligand). Computerized grain counting was performed on discrete regions of the autoradiograms corresponding to areas within laminae I–II, V and X on both sides of the spinal cord; the sciatic nerve's small diameter axons terminate in these areas. With a single exception, there were no changes in binding for any of the ligands in any of the areas at 10 days post surgery in the control animals. The exception was a small increase in kappa binding in laminae I–II on the sham-operated side. After nerve injury, however, there were marked changes (compared to the sham-operated side of the control animals) in the amount of binding for all ligands, and most of these changes were bilateral. Mu binding was significantly increased 2–5 days post injury, bilateral to the injury in laminae V and X but only ipsilateral in laminae I–II. Mu binding in all laminae gradually declined towards control values. By day 10 significant differences remained only in lamina X. Delta binding displayed little change at 2 days post injury but declined gradually thereafter. By day 10 post injury, delta binding was significantly decreased in all three areas; these decreases were bilateral in all areas and approximately equal in laminae V and X but were significantly greater on the nerve-injured side in laminae I–II. Kappa binding displayed a complex pattern of changes at day 2 post injury: a significant increase in ipsilateral laminae I–II and a significant increase in contralateral lamina X but no change on either side in lamina V. There was a rapid decrease in kappa binding in all three areas on both sides of the spinal cord by day 5 post injury, and these decreases were little changed by day 10. At day 5 post injury, these bilateral decreases were approximately equal in all three areas, but at day 10 the decrease in lamina X was significantly greater on the nerve-injured side. The effects on opioid binding may be due to alterations in synaptic activity evoked by spontaneous discharges in primary afferents from the injured nerve, to activity in intraspinal circuitry, or to a pain- or stress-evoked activation of descending pathways. Our observations suggest that rats, and perhaps people, with painful peripheral neuropathies may have altered responses to opiate analgesics, especially for opiates given intrathecally.

Summary The current study adds to a growing body of research on dark personality traits by investigating the moderating role of promotion focus on the relationships among dark triad traits and facets of job performance. Specifically, we investigated the effects of the dark triad (i.e., Machiavellianism, narcissism, and psychopathy) on supervisor ratings of performance, and the moderating effect promotion focus has on those effects. Using field data, we surveyed 549 employees from a manufacturing company in the USA and obtained supervisor ratings of task performance and helping behavior for each employee. We found support for multiple hypotheses, which suggests that managers rated narcissistic and psychopathic employees as having poorer task performance and psychopathic employees as engaging in fewer helping behaviors than employees low in those traits. Furthermore, promotion focus strengthened these negative relationships. We did not find these effects for Machiavellianism. Implications of these findings for future dark personality research as well as the practical implications for managers and organizations are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Abstract When designing jobs, the degree of specialization is a key consideration. Though functional specialization allows workers to develop deep areas of expertise, it also increases the challenge of coordinating their work. In this article, we propose the concepts of stage‐ and site‐based specialization and posit that together they can counteract the divisive effects of functional specialization. Taking advantage of a natural experiment in physician job design at a Massachusetts hospital, we explore the impact of stage‐ and site‐based specialization on coordination and performance outcomes. Building on recent interest in relational approaches to job design, this study is the first to link relational job design to relational outcomes such as coordination. Our findings have practical implications for job design in professional service settings such as education, consulting, and health care. © 2008 Wiley Periodicals, Inc.

INTRODUCTION: Unipolar depressives seem apt to show neuropsychological impairment, particularly involving executive function and memory. Yet, not all depressed patients show such deficits. Major depressive illness shares a high rate of comorbid anxiety disorder, and anxiety disorders also tend to correspond with cognitive difficulties. Consequently, depressed individuals with comorbid anxiety disorders may be inclined to demonstrate greater neuropsychological dysfunction than those without anxiety disorders. METHOD: We compared nonpsychotic depressed inpatients with (n=22) and without comorbid anxiety disorders (n=30) to a group of control subjects (n=38) on a brief but broad battery of neuropsychological tests. Patients were tested during an inpatient admission, and data were collected retrospectively from available records. RESULTS: Both groups of depressed patients showed worse memory function than the controls. Yet, executive dysfunction and psychomotor slowing were specific to the depressed group with comorbid anxiety. The comorbid anxiety group also had more impaired scores than either the nonanxious depressed group or the control group. The depressed group without a comorbid anxiety disorder demonstrated no significant slowing compared to the control group. CONCLUSIONS: Major depressive disorder corresponds with significant memory impairment, regardless of comorbid anxiety disorder. Yet, presence of a comorbid anxiety disorder coincides with deficits involving executive function and psychomotor slowing. Clinical and theoretical relevance of the data is discussed.

OBJECTIVES: To compare the strength of augmented versus nonaugmented fixation techniques for stabilizing vertical shear femoral neck fractures. METHODS: Two surgical screw constructs were tested with and without augmentation using 40 composite femurs: (1) 7.3-mm cannulated screws placed in an inverted triangular configuration and (2) 135-degree dynamic hip screw (DHS). The augmentation consisted of a 2.7-mm locking plate placed on the anterior-inferior femoral neck. Specimens in all 4 groups were tested with load to failure, while failure loads, energy absorbed to failure, and axial stiffness were determined. These data were then analyzed using a two-way (construct × augmentation) analysis of variance. RESULTS: There was no statistically significant interaction between screw construct and augmentation for load to failure (P = 0.11). Augmentation with the 2.7-mm locking plate increased failure loads in both constructs on average by 83% (2409 vs. 4417 N, P < 0.01). Femurs instrumented with cannulated screws had 26% higher loads to failure than those instrumented with DHS (3879 vs. 3087 N, P < 0.01). On average, the augmentation increased energy absorbed to failure by 183% and constructs' stiffness by 35%. CONCLUSIONS: The strength of surgical repairs of the vertical shear femoral neck fractures can be significantly augmented with the 2.7-mm locking plate. The construct with the cannulated screws was significantly stronger than the DHS construct.

We reported that the Os mutation in ROP mice induced a 50% reduction in nephron number, glomerular hypertrophy, and severe glomerulosclerosis. We examined two mouse strains with the Os mutation, ROP Os/+ and C57 Os/+ mice, to determine whether the genetic background influenced the development of glomerulosclerosis. Nephron number was decreased by 50% in both ROP Os/+ and C57 Os/+ mice, and a glomerular volume and labeling index were two- to threefold increased in both. Whereas glomerulosclerosis was severe in ROP Os/+ mice, it was absent or minimal in C57 Os/+ mice. ROP Os/+ glomeruli had two- to threefold more type IV collagen, laminin, and tenascin than C57 Os/+ by immunofluorescence microscopy. Glomerular alpha 1IV collagen and tenascin mRNA levels were increased (2.8- and 1.7-fold) in ROP Os/+ and in C57 Os/+ (1.7- and 1.4-fold) mice. Both ROP Os/+ and C57 Os/+ mice had a slight increase (1.5- and 1.7-fold) in 72-kD collagenase mRNA levels. Whereas laminin B1 mRNA levels were twofold higher in ROP +/+ than in C57 +/+ mice, there was no further change in the presence of the Os mutation. Thus, the response to the Os mutation depended on the mouse strain, since severe glomerulosclerosis occurred only in ROP Os/+ mice, even though cell proliferation and glomerular hypertrophy also were present in C57 Os/+ mice.

PURPOSE: The interrater agreement for and reliability of the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index for categorizing medication errors were determined. METHODS: A letter was sent by the U.S. Pharmacopeia to all 550 contacts in the MEDMARX system user database. Participants were asked to categorize 27 medication scenarios using the NCC MERP index and were randomly assigned to one of three tools (the index alone, a paper-based algorithm, or a computer-based algorithm) to assist in categorization. Because the NCC MERP index accounts for harm and cost, and because categories could be interpreted as substantially similar, study results were analyzed after the nine error categories were collapsed to six. The interrater agreement was measured using Cohen's kappa value. RESULTS: Of 119 positive responses, 101 completed surveys were returned for a response rate of 85%. There were no significant differences in baseline demographics among the three groups. The overall interrater agreement for the participants, regardless of group assignment, was substantial at 0.61 (95% confidence interval [CI], 0.41-0.81). There was no difference among the kappa values of the three study groups and the tools used to aid in medication error classification. When the index was condensed from nine categories to six, the interrater agreement increased with a kappa value of 0.74 (95% CI, 0.56-0.90). CONCLUSION: Overall interrater agreement for the NCC MERP index for categorizing medication errors was substantial. The tool provided to assist with categorization did not influence overall categorization. Further refining of the scale could improve the usefulness and validity of medication error categorization.

We have studied an infant with cloverleaf skull, proptosis, radioulnar synostosis and broad thumbs and great toes diagnosed as Pfeiffer syndrome type 2. However, there were many overlapping findings with Antley-Bixler syndrome. The patient was found to have a G to T mutation in codon 290 exon 7 of the FGFR2 gene leading to a substitution of a cys for the normal trp at this locus. This is the third mutation characterized at this codon; therefore, this locus appears to be a mutational hotspot in the gene. However, the other known mutations lead to a milder, Crouzon-like phenotype. The introduction of an additional cys into a region characterized by immunoglobulin-type loops maintained by cys S-S crosslinking may provide an explanation for the severity of the clinical findings of this child.

OBJECTIVES: To investigate the biomechanical properties of a lateral locked plate alone or in combination with a supplemental medial plate or an intramedullary nail (IMN). METHODS: Intra-articular distal femur fractures with metaphyseal comminution (OTA/AO 33-C) were simulated with a standardized model in 28 synthetic femora and divided into 4 groups. Group I was instrumented with a 4.5-mm lateral locked distal femoral plate alone, group II with a lateral locked plate plus a low-profile precontoured 3.5-mm medial distal tibial plate, group III with a lateral locked plate plus a medial 3.5-mm reconstruction plate, and group IV with a lateral locked plate plus a retrograde IMN. Specimens were then axially loaded and cycled to failure or runout. Outcomes of interest were baseline stiffness, survivability, and cycles to failure. RESULTS: Groups III and IV have a significantly higher baseline stiffness (P < 0.001) when compared with groups I and II. Furthermore, groups III and IV had a higher max load to failure (P < 0.01) when compared with groups I and II. The survivability in groups III and IV was 71% and 100%, respectively, while no specimens in group I or II survived maximum loading. There was no significant difference between group III and IV regarding stiffness, survivability, and cycles to failure. CONCLUSION: When considering fixation for intra-articular distal femur fractures with metaphyseal comminution (OTA/AO 33-C), we found that supplementation of a lateral locked plate with a medial plate or an IMN to be biomechanically superior to lateral locked plating alone regarding stiffness, survivability, and cycles to failure. A low-profile precontoured plate did not add significantly to the construct stiffness in this study.

Intracellular protein levels of p53 and MDM2 have been shown to oscillate in response to ionizing radiation (IR), but the physiological significance of these oscillations remains unclear. The p53-MDM2 negative feedback loop -- the putative cause of the oscillations -- is embedded in a network involving a mutual antagonism (or positive feedback loop) between p53 and AKT. We have shown earlier that this p53-AKT network predicts an all-or-none switching behavior between a pro-survival cellular state (low p53 and high AKT levels) and a pro-apoptotic state (high p53 and low AKT levels). Here, we show that upon exposure to IR, the p53-AKT network can also reproduce the experimentally observed p53 and MDM2 oscillations. The present work is based on the hypothesis that the physiological significance of the experimentally observed oscillations could be found in their role in regulating the switching behavior of the p53-AKT network between pro-survival and pro-apoptotic states. It is shown here that these oscillations are associated with a significant decrease in the threshold level of IR at which switching from a pro-survival to a pro-apoptotic state occurs. Moreover, oscillations in p53 protein levels induce higher levels of expression of p53-target genes compared to non-oscillatory p53, and thus influence cell-fate decisions between cell cycle arrest/DNA damage repair versus apoptosis.