Effect of cell density on thrombin binding to a specific site on bovine vascular endothelial cells.

We studied thrombin binding to proliferating and confluent endothelial cells derived from bovine vascular endothelium. [125]thrombin was incubated with nonconfluent or confluent endothelial cells and both the total amount bound and the amount linked in a 77,000-dalton thrombin-cell complex were determined. Approximately 230,000 molecules of thrombin bound per cell in nonconfluent cultures compared to 12,800 molecules per cell in confluent cultures. Approximately 67,7000 thrombin molecules were bound in an apparently covalent complex, Mr = 77,000, with each cell in sparse cultures, whereas only 4,600 thrombin molecules per cell were bound in this complex with confluent cultures. Similar studies with [125I]thrombin and endothelial cells derived from bovine cornea revealed no difference either in the total amount of thrombin bound or in the amount bound in the 77,000-dalton complex using sparse or confluent cultures. When confluent vascular endothelial cultures were wounded, additional cellular binding sites for the 77,000-dalton complex with thrombin appeared within 24 h. A 237% increase in the amount of thrombin bound to these sites was induced by a wound which resulted in a 20% decrease in cell number in the monolayer. There was no significant increase in thrombin binding to other cellular sites at 24 h. These experiments provide evidence that the first change in thrombin binding after injury is an increase in the cellular sites involved in the 77,000-dalton complex, and suggest that thrombin binding to endothelial cells may be important in the vascular response to injury

Conjugacy classes of p-cycles of type D in alternating groups

We classify the conjugacy classes of p-cycles of type D in alternating groups. This finishes the open cases in arXiv:0812.4628. We also determine all the subracks of those conjugacy classes which are not of type D.Comment: Second paragraph of subsection 2.2 rewritten. 4-th sentence of subsection 2.4 rewritten. More explanations added in Remark 2.4. Lemma 2.5 and Corollary 2.7 added. Appendix removed and put it as Remark 3.1. Remark 3.2 (former 3.1) reorganized. References: [Da], [EGSS], [H], [IS] added, [GPPS] removed. Communications in Algebra (2014

Therapeutic Vaccines and Antibodies for Treatment of Orthopoxvirus Infections

Despite the eradication of smallpox several decades ago, variola and monkeypox viruses still have the potential to become significant threats to public health. The current licensed live vaccinia virus-based smallpox vaccine is extremely effective as a prophylactic vaccine to prevent orthopoxvirus infections, but because of safety issues, it is no longer given as a routine vaccine to the general population. In the event of serious human orthopoxvirus infections, it is important to have treatments available for individual patients as well as their close contacts. The smallpox vaccine and vaccinia immune globulin (VIG) were used in the past as therapeutics for patients exposed to smallpox. VIG was also used in patients who were at high risk of developing complications from smallpox vaccination. Thus post-exposure vaccination and VIG treatments may again become important therapeutic modalities. This paper summarizes some of the historic use of the smallpox vaccine and immunoglobulins in the post-exposure setting in humans and reviews in detail the newer animal studies that address the use of therapeutic vaccines and immunoglobulins in orthopoxvirus infections as well as the development of new therapeutic monoclonal antibodies

The experience of adolescents participating in a randomised clinical trial in the field of mental health: a qualitative study

Background This descriptive study aimed to investigate adolescents’ motivations for participating in a randomised controlled trial (RCT), to explore the understanding that the young people had regarding a number of aspects of the trial design, to examine whether or not they found participation in the trial to be acceptable and what affected this, and to identify whether and how the young people felt that their participation in the RCT impacted on their experience of therapy and on therapeutic change. Methods Seventy-six adolescents who were taking part in a large-scale RCT to evaluate the clinical and cost effectiveness of psychological therapies for depression were interviewed at two time-points after completing therapy. The semi-structured interviews, which included a focus on the young people’s experience of the research study, were analysed using framework analysis. Results The vast majority of adolescents found it acceptable to participate in the clinical trial, and many agreed to participate for reasons of ‘conditional altruism’. However consent was often given without great understanding of the key elements of the trial, including the difference between treatment arms and the randomisation process. Although the adolescents were largely positive about their experiences from taking part, the study raises questions about whether clinical outcomes may be influenced by participation in the research elements of the trial. Conclusions Although adolescents are under-represented in clinical trials, those who do participate are generally positive about the experience; however, careful thought needs to be given to key elements of the trial design and the potential impact of the research participation on clinical outcomes

Identifying Second Language Speech Tasks and Ability Levels for Successful Nurse Oral Interaction with Patients in a Linguistic Minority Setting::An Instrument Development Project

One of the most demanding situations for members of linguistic minorities is a conversation between a health professional and a patient, a situation that frequently arises for linguistic minority groups in North America, Europe, and elsewhere. The present study reports on the construction of an oral interaction scale for nurses serving linguistic minorities in their second language (L2). A mixed methods approach was used to identify and validate a set of speech activities relating to nurse interactions with patients and to derive the L2 ability required to carry out those tasks. The research included an extensive literature review, the development of an initial list of speech tasks, and validation of this list with a nurse focus group. The retained speech tasks were then developed into a questionnaire and administered to 133 Quebec nurses who assessed each speech task for difficulty in an L2 context. Results were submitted to Rasch analysis and calibrated with reference to the Canadian Language Benchmarks, and the constructs underlying the speech tasks were identified through exploratory and confirmatory factor analyses. Results showed that speech tasks dealing with emotional aspects of caregiving and conveying health-specific information were reported as being the most demanding in terms of L2 ability, and the most strongly associated with L2 ability required for nurse-patient interactions. Implications are discussed with respect to the development and use of assessment instruments to facilitate L2 workplace training for health care professionals

Prescriptions for Bedtime Sedatives After the Introduction of a General Admission Order Set at an Academic Health Center: The Potential and Pitfalls of Order Sets.

OBJECTIVE: This study describes the impact of modifications to a general admission order set on physician prescribing of 2 as-needed or pro re nata (PRN) bedtime sedatives. METHODS: The hospitalists at our institution have used a general medical admission order set since 2005. Zolpidem was the only as-needed (PRN) bedtime sedative option on the order set until trazodone was added in December 2008. Trazodone is preferred over zolpidem in the geriatric population. We identified patients admitted by the hospitalists between January 2007 and August 2013 who were prescribed with either zolpidem or trazodone as a PRN sedative. Patient demographics, date and time of the order, and number of sedative doses administered during the hospitalization were recorded. Orders placed within 12 hours of admission were attributed to admission orders. RESULTS: Between 2007 and 2013, the number of patients admitted by the hospitalists with an order for PRN trazodone on admission increased by 18-fold. During the same period, the number of admissions by the hospitalists increased by 2.3 times. Zolpidem orders exceeded those for trazodone in all age groups until 2008. After the addition of trazodone, its use exceeded that of zolpidem. Almost half (48%) of all patients did not have a dose of the PRN trazodone administered. CONCLUSIONS: Although order sets can be leveraged to align practitioners with established guidelines, the expediency of using medications on an order set may overcome physicians\u27 clinical judgment. The content of an order set therefore deserves careful scrutiny before implementation

Vaccinia Virus Serpin-1 Deletion Mutant Exhibits a Host Range Defect Characterized by Low Levels of Intermediate and Late mRNAs

AbstractOrthopoxviruses encode three serpin homologs—SPI-1, SPI-2 and SPI-3—of which SPI-2 has been well characterized as an inhibitor of ICE-like proteases. A rabbitpox virus SPI-1 deletion mutant exhibited a host range restriction in human lung A549 and pig kidney 15 cell lines that was attributed to apoptosis. Here we report that replication of a vaccinia virus SPI-1 deletion mutant (ΔSPI-1) was restricted in primary human keratinocytes as well as A549 cells. Although chromatin condensation was detected in some A549 cells, other morphological or biochemical signs of apoptosis including DNA fragmentation, cleavage of poly(ADP-ribose)polymerase or nuclear mitotic apparatus protein, or caspase 3 activation were not found. Moreover, ΔSPI-1 protected A549 cells from apoptosis induced by tumor necrosis factor, whereas the corresponding ΔSPI-2 mutant did not. Further studies indicated undiminished amounts of vaccinia virus early mRNA and replicated DNA in the absence of the SPI-1 product. However, there were reduced amounts of viral intermediate and late mRNAs, viral late proteins, cleaved core proteins, and virus particles. These data suggested that apoptosis is not the determining factor in the host range restriction of ΔSPI-1 and that the SPI-1 gene product is needed to allow efficient expression of intermediate and late genes in A549 cells

Student-generated e-learning for clinical education

Background Within clinical education, e-learning facilitates a standardised learning experience to augment the clinical experience while enabling learner and teacher flexibility. With the shift of students from consumers to creators, student-generated content is expanding within higher education; however, there is sparse literature evaluating the impact of student-developed e-learning within clinical education. The aim of this study was to implement and evaluate a student-developed e-learning clinical module series within ambulatory care clinical pharmacy experiences. Methods Three clinical e-learning modules were developed by students for use prior to clinical experiences. E-learning modules were created by fourth-year professional pharmacy students and reviewed by pharmacy faculty members. A pre-/post-assessment was performed to evaluate knowledge comprehension before and after participating in the e-learning modules. Additionally, a survey on student perceptions of this educational tool was performed at the end of the clinical experience. There is sparse literature evaluating the impact of student-developed e-learning within clinical education Results Of the 31 students eligible for study inclusion, 94 per cent participated in both the pre- and post-assessments. The combined post-assessment score was significantly improved after participating in the student-developed e-learning modules (p = 0.008). The student perception survey demonstrated positive perceptions of e-learning within clinical education. Discussion Student-generated e-learning was able to enhance knowledge and was positively perceived by learners. As e-learning continues to expand within health sciences education, students can be incorporated into the development and execution of this educational tool

Analysis of a Standardized Perioperative Pain Management Order Set in Highly Opioid-Tolerant Patients

Objective: The aim was to assess a standardized order set for perioperative pain management in highly opioid-tolerant patients undergoing elective orthopedic surgery.Methods: This retrospective chart review evaluated a pain order set in highly opioid-tolerant patients undergoing elective total knee or total hip arthroplasty from January 2010 through August 2012. Based on the date of the surgery, patients were allocated into preimplementation or postimplementation order set groups. The primary outcome assessed whether an adjustment in daily opioid dosage was required within the first 48 hours postoperatively. Secondary outcomes included pain scores, length of hospitalization, and safety outcomes.Results: Sixty patients were included in the analysis. An adjustment to postoperative opioid therapy occurred in 62% of the patients in the preimplementation group and in 56% of postimplementation group patients (P = 0.786). There were no differences in median pain scores 48 hours postoperatively (P = 0.348). Cumulative toxicity was increased after order set implementation compared with previous patients (44% versus 5%, P \u3c 0.005); however, opioid doses held for sedation was the only individual toxicity to reach statistical significance (P = 0.011).Conclusions: This study is the first to evaluate a standardized order set for pain management in highly opioid-tolerant patients undergoing elective orthopedic surgery. The order set demonstrated similar efficacy to previous treatment modalities, but opioid-induced sedation was of concern with the order set. After the initial analysis, the order set was modified to minimize opioid-induced sedation. Continual safety analysis is warranted for quality improvement to enhance perioperative pain management in highly opioid-tolerant patients

A survey of trainees’ perspectives on epidural training in the United Kingdom

Background: Establishment of epidural analgesia is one of the most difficult technical skills in which to become proficient. We explored the current United Kingdom system of training in epidural insertion amongst trainee members of the Obstetric Anaesthetists’ Association (OAA). Methods: An electronic questionnaire was sent to 452 OAA trainee members in May 2012. Questions were based upon own personal experience, challenges currently faced and the use of epidural simulation to enhance training. Results: Although the majority felt ready and prepared when initially performing epidurals solo, 66% found the experience very stressful and 25% felt under considerable time pressure. Although senior support was readily available, 36% felt uncertain much of the time and 9% were unsure when to call for help. The European Working Time Directive was felt to have impacted upon training by 54% of respondents. 40% believe that there exists more challenging patients who require more experienced operators. Although 53% had used an epidural simulator previously, 84% would recommend its use for trainees and 49% would support simulator use as a compulsory element of training. Conclusions: In spite of changes to the medical profession, there appears to be a robust system of training for epidural analgesia. However, there still exists the need to reduce the impact of the learning curve upon workplace stress for trainees. Whether this involves increased direct supervision for more than just the bare minimum, structured feedback tools to enhance the supervisor/trainee experience or the use of high-fidelity epidural simulation remains to be seen