Reduction in DNA binding activity of the transcription factor Pax-5a in B lymphocytes of aged mice

Aging has been associated with intrinsic changes of the humoral immune response, which may lead to an increased occurrence of autoimmune disorders and pathogenic susceptibility. The transcription factor Pax-5 is a key regulator of B cell development. Pax-5a/B cell-specific activator protein and an alternatively spliced isoform, Pax-Sd, may have opposing functions in transcriptional regulation due to the lack of a transactivation domain in Pax-Sd. To study B cell-specific changes that occur during the aging process, we investigated expression patterns of Pax-Sa and Sd in mature B cells of young and aged mice. RNase protection assays showed a similar transcriptional pattern for both age groups that indicates that aging has no affect on transcription initiation or alternative splicing for either isoform, In contrast, a significant reduction in the DNA binding activity of Pax-Sa but not Pax-Sd protein was observed in aged B cells in vitro, while Western blot analyses showed that similar levels of Pax-Sa and Sd proteins were present in both age groups. The observed decrease in Pax-Sa binding activity correlated with changes in expression of two Pax-5 target genes in aged B cells, Expression of the Ig J chain and the secreted form of Ig mu, which are both known to be suppressed by Pax-Sa in mature B cells, were increased in B cells of aged mice, Together, our studies suggest that changes associated with the aging phenotype cause posttranslational modification(s) of Pax-Sa but not Pax-Sd, which may lead to an abnormal B cell phenotype in aged mice, associated with elevated levels of J chain, and secretion of IgM

Development of a Fundamental Depth-Dependent Neutron Dosimetry Model

Current neutron dosimetry methods rely on the assumption that charged particle equilibrium (CPE) is established within the tissue medium. This maintains that the kinetic energy transferred to the medium (KERMA) is equivalent to absorbed dose. However, this assumption is only valid for large volumes such as the whole body. For small volumes near the surface of the skin, CPE does not always exist. The aim of this study was to develop a deterministic, depth-dependent neutron dosimetry model that accounts for the lack in CPE at shallow depths. The bulk of the model was developed from first principles and existing neutron cross-sectional data. A series of simulations were constructed utilizing MCNP to investigate the relationship between KERMA and absorbed dose with depth in tissue. From this work, a method to account for fractional charged particle equilibrium is proposed and incorporated in a first principles neutron dosimetry model

PAMTRAK: A system to monitor high value objects and personnel in restricted areas

The US Department of Energy (DOE) uses sensitive or classified parts and material that must be protected and accounted for. The authors believe there is a need for an automated system that can help protect and monitor these parts and material. In response to this need Sandia National Laboratories (SNL) has developed a real-time personnel and material tracking system called PAMTRAK that has been installed at selected DOE facilities. PAMTRAK safeguards sensitive parts and material by tracking tags worn by personnel and by monitoring sensors attached to the parts or material. This paper describes the goals when designing PAMTRAK, the PAMTRAK system components, the current installations, and the benefits a site can expect when using PAMTRAK

Say Her Name: Resisting Police Brutality Against Black Women

Say Her Name sheds light on Black women’s experiences of police violence in an effort to support a gender-inclusive approach to racial justice that centers all Black lives equally. It is our hope that this document will serve as a tool for the resurgent racial justice movement to mobilize around the stories of Black women who have lost their lives to police violence ...Our goal is not to offer a comprehensive catalog of police violence against Black women – indeed, it would be impossible to do so as there is currently no accurate data collection on police killings nationwide, no readily available database compiling a complete list of Black women’s lives lost at the hands of police, and no data collection on sexual or other forms of gender- and sexuality- based police violence. Moreover, the media’s exclusive focus on police violence against Black men makes finding information about Black women of all gender identities and sexualities much more difficult. Given these limitations, our goal is simply to illustrate the reality that Black women are killed and violated by police with alarming regularity. Equally important, our hope is to call attention to the ways in which this reality is erased from our demonstrations, our discourse, and our demands to broaden our vision of social justice. As a result of the paucity of data, the stories of police violence included in this document are essentially either gathered through online research or cases that have come to the attention of the report’s authors. Many cases have never seen the light of day, and even those that have surfaced momentarily have received little sustained national or local attention. Significantly more women who have been killed by the police are missing from these pages, but their lives are certainly no less valuable

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

PEGylated gold nanoparticles (AuNPs) have an extended circulation time after intravenous injection in vivo and exhibit favorable properties for biosensing, diagnostic imaging, and cancer treatment. No impact of PEGylated AuNPs on the barrier forming properties of endothelial cells (ECs) has been reported, but recent studies demonstrated that unexpected effects on erythrocytes are observed. Almost all studies to date have been with static-cultured ECs. Herein, ECs maintained under physiological cyclic stretch and flow conditions and used to generate a blood–brain barrier model were exposed to 20 nm PEGylated AuNPs. An evaluation of toxic effects, cell stress, the release profile of pro-inflammatory cytokines, and blood–brain barrier properties showed that even under physiological conditions no obvious effects of PEGylated AuNPs on ECs were observed. These findings suggest that 20 nm-sized, PEGylated AuNPs may be a useful tool for biomedical applications, as they do not affect the normal function of healthy ECs after entering the blood stream

Aromatherapy Use for Post-operative Nausea and Vomiting for Patients Undergoing Same-day Surgeries

Description: Nausea and vomiting are frequent complications of anesthesia post-operatively. There is an increased prevalence of postoperative nausea and vomiting (PONV) in patients undergoing intra-abdominal and gynecologic surgeries. Many injectable and enteral medications are available for the prevention and treatment of PONV, each with the potential for side effects. Utilization of medications requires a provider order, which has the potential to delay initiation of therapy. The use of aromatherapy via inhalation for the treatment of PONV has been shown to eliminate nausea in up to 85% of patients. Patients have reported perceived effectiveness and favorable improvement with the use of aromatherapy for post-operative nausea. Aromatherapy products have been shown to be well tolerated with no adverse effects, drug interactions, or contraindications. Aim: To study the effectiveness of QueaseEASE® aromatherapy pods in the treatment of PONV in patients undergoing same-day intra-abdominal surgeries or hysterectomies. Intervention: We distributed 100 QueaseEASE® pods to patients scheduled for same-day intra-abdominal surgeries or hysterectomies. Informed consent was obtained preoperatively. Up to 24 hours after recovery, patients were instructed to document their episodes of nausea, severity at onset and severity 30 minutes after pod use. The severity of nausea was recorded using the visual analogue scale (0-100) where zero indicates no nausea and 100 indicates unbearable nausea. Use of traditional antiemetic medications was not excluded pursuant to individual provider practice. Data for concomitant antiemetic medication use was also recorded, including medication type, dose and frequency. Summary of Results: Results pending

“It’s hard to tell”. The challenges of scoring patients on standardised outcome measures by multidisciplinary teams: a case study of Neurorehabilitation

Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management

Reinforcing medical authority: clinical ethics consultation and the resolution of conflicts in treatment decisions

Despite substantial efforts in the past 15 years to professionalise the field of clinical ethics consultation, sociologists have not re‐examined past hypotheses about the role of such services in medical decision‐making and their effect on physician authority. In relation to those hypotheses, we explore two questions: (i) What kinds of issues does ethics consultation resolve? and (ii) what is the nature of the resolution afforded by these consults? We examined ethics consultation records created between 2011 and mid‐2015 at a large tertiary care US hospital and found that in most cases, the problems addressed are not novel ethical dilemmas as classically conceived, but are instead disagreements between clinicians and patients or their surrogates about treatment. The resolution offered by a typical ethics consultation involves strategies to improve communication rather than the parsing of ethical obligations. In cases where disagreements persist, the proposed solution is most often based on technical clinical judgements, reinforcing the role of physician authority in patient care and the ethical decisions made about that care.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154312/1/shil13003.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154312/2/shil13003_am.pd

“Being Guided”: What Oncofertility Patients’ Decisions Can Teach Us About the Efficacy of Autonomy, Agency, and Decision-Making Theory in the Contemporary Critical Encounter

Recent research on patient decision-making reveals a disconnect between theories of autonomy, agency, and decision-making and their practice in contemporary clinical encounters. This study examines these concepts in the context of female patients making oncofertility decisions in the United Kingdom in light of the phenomenon of “being guided.” Patients experience being guided as a way to cope with, understand, and defer difficult treatment decisions. Previous discussions condemn guided decision-making, but this research suggests that patients make an informed, autonomous decision to be guided by doctors. Thus, bioethicists must consider the multifaceted ways that patients enact their autonomy in medical encounters

A Novel Solid-Phase Site-Specific PEGylation Enhances the In Vitro and In Vivo Biostabilty of Recombinant Human Keratinocyte Growth Factor 1

Keratinocyte growth factor 1 (KGF-1) has proven useful in the treatment of pathologies associated with dermal adnexae, liver, lung, and the gastrointestinal tract diseases. However, poor stability and short plasma half-life of the protein have restricted its therapeutic applications. While it is possible to improve the stability and extend the circulating half-life of recombinant human KGF-1 (rhKGF-1) using solution-phase PEGylation, such preparations have heterogeneous structures and often low specific activities due to multiple and/or uncontrolled PEGylation. In the present study, a novel solid-phase PEGylation strategy was employed to produce homogenous mono-PEGylated rhKGF-1. RhKGF-1 protein was immobilized on a Heparin-Sepharose column and then a site-selective PEGylation reaction was carried out by a reductive alkylation at the N-terminal amino acid of the protein. The mono-PEGylated rhKGF-1, which accounted for over 40% of the total rhKGF-1 used in the PEGylation reaction, was purified to homogeneity by SP Sepharose ion-exchange chromatography. Our biophysical and biochemical studies demonstrated that the solid-phase PEGylation significantly enhanced the in vitro and in vivo biostability without affecting the over all structure of the protein. Furthermore, pharmacokinetic analysis showed that modified rhKGF-1 had considerably longer plasma half-life than its intact counterpart. Our cell-based analysis showed that, similar to rhKGF-1, PEGylated rhKGF-1 induced proliferation in NIH 3T3 cells through the activation of MAPK/Erk pathway. Notably, PEGylated rhKGF-1 exhibited a greater hepatoprotection against CCl4-induced injury in rats compared to rhKGF-1