Estrogen-Dependent Expression and Subcellular Localization of the Tight Junction Protein Claudin-4 in HEC-1A Endometrial Cancer Cells

Endometrial cancer is the most common female reproductive cancer in the United States and is associated with deregulated tight junction protein expression. Given the highly estrogen-responsive nature of this tissue, we investigated the effects of estrogen and its agonist, 4-OH TAM, on the expression and subcellular localization of the tight junction protein claudin-4 (CLDN-4), in HEC-1A endometrial cancer cells. In untreated HEC-1A cells, we observed dramatic overexpression of claudin-4 protein. In addition, differential detergent extraction analysis indicated that claudin-4 was localized primarily in the membrane but also found in the cytosolic, nuclear and cytoskeletal fractions. Upon exposure of HEC-1A to estradiol (E2), we observed a biphasic effect both on the overall expression of claudin-4 protein and on its cytosolic and cytoskeletal presence as demonstrated by immunoblot analysis. Immunofluorescence analysis also revealed a biphasic effect of E2 on claudin-4 expression. In contrast, we observed no changes in expression levels nor in the subcellular distribution patterns of claudin-4 in HEC-1A cells treated with different concentrations of 4-OH TAM. The intracellular presence of CLDN-4 coupled with the biphasic effects of E2 on CLDN-4 expression in the cytoskeleton suggest that this protein may be involved in cell signaling to and from TJs

RH-TRU Waste Inventory Characterization by AK and Proposed WIPP RH-TRU Waste Characterization Objectives

The U.S. Department of Energy (DOE)-Carlsbad Field Office (CBFO) has developed draft documentation to present the proposed Waste Isolation Pilot Plant (WIPP) remote-handled (RH-) transuranic (TRU) waste characterization program to its regulators, the U.S. Environmental Protection Agency and the New Mexico Environment Department. Compliance with Title 40, Code of Federal Regulations, Parts 191 and 194; the WIPP Land Withdrawal Act (PL 102-579); and the WIPP Hazardous Waste Facility Permit, as well as the Certificates of Compliance for the 72-B and 10-160B Casks, requires that specific waste parameter limits be imposed on DOE sites disposing of TRU waste at WIPP. The DOE-CBFO must control the sites' compliance with the limits by specifying allowable characterization methods. As with the established WIPP contact handled TRU waste characterization program, the DOE-CBFO has proposed a Remote-Handled TRU Waste Acceptance Criteria (RH-WAC) document consolidating the requirements from various regulatory drivers and proposed allowable characterization methods. These criteria are consistent with the recommendation of a recent National Academy Sciences/National Research Council to develop an RH-TRU waste characterization approach that removes current self imposed requirements that lack a legal or safety basis. As proposed in the draft RH-WAC and other preliminary documents, the DOE-CBFO RH-TRU waste characterization program proposes the use of acceptable knowledge (AK) as the primary method for obtaining required characterization information. The use of AK involves applying knowledge of the waste in light of the materials or processes used to generate the waste. Documentation, records, or processes providing information about various attributes of a waste stream, such as chemical, physical, and radiological properties, may be used as AK and may be applied to individual waste containers either independently or in conjunction with radiography, visual examination, assay, and other sampling and analytical data. RH-TRU waste cannot be shipped to WIPP on the basis of AK alone if documentation demonstrating that all of the prescribed limits in the RH-WAC are met is not available, discrepancies exist among AK source documents describing the same waste stream and the most conservative assumptions regarding those documents indicates that a limit will not be met, or all required data are not available for a given waste stream

Antibodies against Lysophosphatidic Acid Protect against Blast-Induced Ocular Injuries

Exposure to blast overpressure waves is implicated as the major cause of ocular injuries and resultant visual dysfunction in veterans involved in recent combat operations. No effective therapeutic strategies have been developed so far for blast-induced ocular dysfunction. Lysophosphatidic acid (LPA) is a bioactive phospholipid generated by activated platelets, astrocytes, choroidal plexus cells, and microglia and is reported to play major roles in stimulating inflammatory processes. The levels of LPA in the cerebrospinal fluid have been reported to increase acutely in patients with traumatic brain injury (TBI) as well as in a controlled cortical impact (CCI) TBI model in mice. In the present study, we have evaluated the efficacy of a single intravenous administration of a monoclonal LPA antibody (25 mg/kg) given at 1 h post-blast for protection against injuries to the retina and associated ocular dysfunctions. Our results show that a single 19 psi blast exposure significantly increased the levels of several species of LPA in blood plasma at 1 and 4 h post-blast. The anti-LPA antibody treatment significantly decreased glial cell activation and preserved neuronal cell morphology in the retina on day 8 after blast exposure. Optokinetic measurements indicated that anti-LPA antibody treatment significantly improved visual acuity in both eyes on days 2 and 6 post-blast exposure. Anti-LPA antibody treatment significantly increased rod photoreceptor and bipolar neuronal cell signaling in both eyes on day 7 post-blast exposure. These results suggest that blast exposure triggers release of LPAs, which play a major role promoting blast-induced ocular injuries, and that a single early administration of anti-LPA antibodies provides significant protection

The Remote-Handled TRU Waste Program

RH TRU Waste is radioactive waste that requires shielding in addition to that provided by the container to protect people nearby from radiation exposure. By definition, the radiation dose rate at the outer surface of the container is greater than 200 millirem per hour and less than 1,000 rem per hour. The DOE is proposing a process for the characterization of RH TRU waste planned for disposal in the WIPP. This characterization process represents a performance-driven approach that satisfies the requirements of the New Mexico Hazardous Waste Act, the Environmental Protection Agency (EPA) regulations for WIPP long-term performance, the transportation requirements of the Nuclear Regulatory Commission (NRC) and the Department of Transportation, as well as the technical safety requirements of RH TRU waste handling. The transportation, management and disposal of RH TRU waste is regulated by external government agencies as well as by the DOE itself. Externally, the characterization of RH-TRU waste for disposal at the WIPP is regulated by 20.4.1.500 New Mexico Administrative Code (incorporating 40 CFR 261.13) for the hazardous constituents and 40 CFR 194.24 for the radioactive constituents. The Nuclear Regulatory Commission certifies the shipping casks and the transportation system must meet DOT regulations. Internally, the DOE evaluates the environmental impacts of RH TRU waste transportation, handling and disposal through its National Environmental Policy Act program. The operational safety is assessed in the RH TRU Waste Safety Analysis Report, to be approved by the DOE. The WIPP has prepared a modification request to the Hazardous Waste Facility Permit that includes modifications to the WIPP facility for the safe receipt and handling of RH TRU waste and the addition of an RH TRU waste analysis plan. Modifications to the facility include systems and equipment for safe handling of RHTRU containers. Two shipping casks are to be used to optimize RH TRU was te throughput: the RH-72B and the CNS 10-160B transportation casks. Additionally, a draft Notification of Proposed Change to the EPA 40 CFR 194 Certification of the WIPP has been prepared, which contains a proposal for the RH TRU characterization program for compliance with the EPA requirements

The effect of crack orientation on the nonlinear interaction of a P wave with an S wave

Cracks, joints, fluids, and other pore-scale structures have long been hypothesized to be the cause of the large elastic nonlinearity observed in rocks. It is difficult to definitively say which pore-scale features are most important, however, because of the difficulty in isolating the source of the nonlinear interaction. In this work, we focus on the influence of cracks on the recorded nonlinear signal and in particular on how the orientation of microcracks changes the strength of the nonlinear interaction. We do this by studying the effect of orientation on the measurements in a rock with anisotropy correlated with the presence and alignment of microcracks. We measure the nonlinear response via the traveltime delay induced in a low-amplitude P wave probe by a high-amplitude S wave pump. We find evidence that crack orientation has a significant effect on the nonlinear signal

Cosmetic outcomes and quality of life in children with cardiac implantable electronic devices

BackgroundAxillary implant location is an alternative implant location in patients for cardiac implantable electronic devices (CIEDs) for the purposes of improved cosmetic outcome. The impact from the patient’s perspective is unknown. The purpose of this study was to compare scar perception scores and quality of life (QOL) in pediatric patients with axillary CIED implant location versus the standard infraclavicular approach.MethodsThis is a multicenter prospective study conducted at eight pediatric centers and it includes patients aged from 8 to 18 years with a CIED. Patients with prior sternotomy were excluded. Scar perception and QOL outcomes were compared between the infraclavicular and axillary implant locations.ResultsA total of 141 patients (83 implantable cardioverter defibrillator [ICD]/58 pacemakers) were included, 55 with an axillary device and 86 with an infraclavicular device. Patients with an ICD in the axillary position had better perception of scar appearance and consciousness. Patients in the axillary group reported, on average, a total Pediatric QOL Inventory score that was 6 (1, 11) units higher than the infraclavicular group, after adjusting for sex and race (P = 0.02).ConclusionsQOL is significantly improved in axillary in comparison to the infraclavicular CIED position, regardless of device type. Scar perception is improved in patients with ICD in the axillary position.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147032/1/pace13522.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147032/2/pace13522_am.pd

Acute kidney injury in critically Ill children and young adults with suspected SARS-CoV2 infection

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background: We aimed to study the association of suspected versus confirmed infection with the novel SARS-CoV2 virus with the prevalence of acute kidney injury (AKI) in critically ill children. Methods: Sequential point-prevalence study of children and young adults aged 7 days to 25 years admitted to intensive care units under investigation for SARS-CoV2 infection. AKI was staged in the first 14 days of enrollment using KDIGO creatinine-based staging. SARS-CoV2 positive (CONFIRMED) were compared to SUSPECTED (negative or unknown). Outcome data was censored at 28-days. Results: In 331 patients of both sexes, 179 (54.1%) were CONFIRMED, 4.2% (14) died. AKI occurred in 124 (37.5%) and severe AKI occurred in 63 (19.0%). Incidence of AKI in CONFIRMED was 74/179 (41.3%) versus 50/152 (32.9%) for SUSPECTED; severe AKI occurred in 35 (19.6%) of CONFIRMED and 28 (18.4%) of SUSPECTED. Mortality was 6.2% (n = 11) in CONFIRMED, but 9.5% (n = 7) in those CONFIRMED with AKI. On multivariable analysis, only Hispanic ethnicity (relative risk 0.5, 95% CI 0.3-0.9) was associated with less AKI development among those CONFIRMED. Conclusions: AKI and severe AKI occur commonly in critically ill children with SARS-CoV2 infection, more than double the historical standard. Further investigation is needed during this continuing pandemic to describe and refine the understanding of pediatric AKI epidemiology and outcomes. Trial registration: NCT01987921. Impact: What is the key message of the article? AKI occurs in children exposed to the novel SARS-CoV2 virus at high prevalence (~40% with some form of AKI and 20% with severe AKI). What does it add to the existing literature? Acute kidney injury (AKI) occurs commonly in adult patients with SARS-CoV2 (COVID), very little data describes the epidemiology of AKI in children exposed to the virus. What is the impact? A pediatric vaccine is not available; thus, the pandemic is not over for children. Pediatricians will need to manage significant end-organ ramifications of the novel SARS-CoV2 virus including AKI

Work-life balance in the police: the development of a self-management competency framework

Purpose Addressing a gap in the current work–life balance (WLB) literature regarding individual-focused approaches to inform interventions, we elicited behaviors used to self-manage WLB to draw up a competency-based WLB framework for relevant learnable knowledge, skills, and abilities (KSAs; Hoffmann, Eur J Ind Train 23:275–285, 1999) and mapping this against extant WLB frameworks. Design/Methodology/Approach Our participants were from a major UK police force, which faces particular challenges to the work–life interface through job demands and organizational cutbacks, covering a range of operational job roles, including uniformed officers and civilian staff. We took a mixed methods approach starting with semi-structured interviews to elicit 134 distinct behaviors (n = 20) and used a subsequent card sort task (n = 10) to group these into categories into 12 behavioral themes; and finally undertook an online survey (n = 356) for an initial validation. Findings Item and content analysis reduced the behaviors to 58, which we analyzed further. A framework of eight competencies fits the data best; covering a range of strategies, including Boundary Management, Managing Flexibility, and Managing Expectations. Implications The WLB self-management KSAs elicited consist of a range of solution-focused behaviors and strategies, which could inform future WLB-focused interventions, showing how individuals may negotiate borders effectively in a specific environment. Originality/Value A competence-based approach to WLB self-management is new, and may extend existing frameworks such as Border Theory, highlighting a proactive and solution-focused element of effective behaviors