Rescue of NLRC5 expression restores antigen processing machinery in head and neck cancer cells lacking functional STAT1 and p53.

The antigen processing machinery (APM) components needed for a tumor cell to present an antigen to a T cell are expressed at low levels in solid tumors, constituting an important mechanism of immune escape. More than most other solid tumors, head and neck squamous cell carcinoma (HNSCC) cells tend to have low APM expression, rendering them insensitive to immune checkpoint blockade and most other forms of immunotherapy. In HNSCC, this APM deficiency is largely driven by high levels of EGFR and SHP2, leading to low expression and activation of STAT1; however, recent studies suggest that p53, which is often mutated in HNSCCs, may also play a role. In the current study, we aimed to investigate the extent to which STAT1 and p53 individually regulate APM component expression in HNSCC cells. We found that in cells lacking functional p53, APM expression could still be induced by interferon-gamma or DNA-damaging chemotherapy (cisplatin) as long as STAT1 expression remained intact; when both transcription factors were knocked down, APM component expression was abolished. When we bypassed these deficient pathways by rescuing the expression of NLRC5, APM expression was also restored. These results suggest that dual loss of functional STAT1 and p53 may render HNSCC cells incapable of processing and presenting antigens, but rescue of downstream NLRC5 expression may be an attractive strategy for restoring sensitivity to T cell-based immunotherapy.

Ethical tension in nursing education: a challenge for faculty values and beliefs.

OBJECTIVES: The culture of the academic setting can be fraught with tension filled ethical situations challenging faculty relations with students and colleagues. Therefore, the purpose of this qualitative study was to identify the process that occurs when nursing faculty encounter tension filled situations affecting their ethical values and beliefs in the education setting. METHODS: A grounded theory approach was employed to achieve data saturation from interviews of thirteen faculty representing eight colleges/universities in three states of the MidAtlantic region of the United States. RESULTS: The Basic Social Psychological Process that emerged from the data demonstrated faculty efforts toward safeguarding profession, student, and self. Three concepts: experiencing, identifying, and resolving evolved. CONCLUSIONS: Data evidenced that ethical tension negatively influences one's work-life balance, and civility with faculty and students. Implications for balancing these influences and working toward a harmonious environment are provided.

Courageous caring conversations: Promoting faculty wellbeing.

Courageous Caring Conversations was designed to support faculty wellbeing and a culture of caring and civility in nursing academe. This innovative strategy involves an adaptation of Schwartz Healthcare Rounds for nursing education to establish a culture of respect and caring among nursing faculty. The process is guided by Chinn's Peace and Power process. Courageous Caring Conversations encourage faculty to discuss ethical dilemmas and challenging academic or collegial situations that occur over the course of the semester. The process begins with a shared meal offering an informal opportunity for faculty to connect and establish relatedness. Faculty then enter into a shared discussion intended to provide a venue to debrief the challenges of the semester with the goal of deepening understanding, empathy, and compassion among faculty. This practice supports the development of a healthy academic workplace where conflict is viewed as transformative and open communication and civility flourish.

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma.

Phase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6 mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary objectives were to: (1) evaluate histological evidence of anti-tumor activity and (2) evaluate recurrence-free survival (RFS) and OS. Twenty melanoma patients were randomized to Group A (11 patients) or B (9 patients). Two Group B patients did not receive IC due to persistent disease following surgery. Six of 18 IC-treated patients remained free of recurrence, with a median RFS of 5.7 months (95% confidence interval (CI) 1.8-not reached). The 24-month RFS rate was 38.9% (95% CI 17.5-60.0%). The median follow-up of surviving patients was 50.0 months (range: 31.8-70.4). The 24-month OS rate was 65.0% (95% CI 40.3-81.5%). Toxicities were similar to those previously reported. Exploratory tumor-infiltrating lymphocyte (TIL) analyses suggest prognostic value of TILs from Group A patients. Prolonged tumor-free survival was seen in some melanoma patients at high risk for recurrence who were treated with IC.

Phase I study to evaluate toxicity and feasibility of intratumoral injection of α-gal glycolipids in patients with advanced melanoma.

Effective uptake of tumor cell-derived antigens by antigen-presenting cells is achieved pre-clinically by in situ labeling of tumor with α-gal glycolipids that bind the naturally occurring anti-Gal antibody. We evaluated toxicity and feasibility of intratumoral injections of α-gal glycolipids as an autologous tumor antigen-targeted immunotherapy in melanoma patients (pts). Pts with unresectable metastatic melanoma, at least one cutaneous, subcutaneous, or palpable lymph node metastasis, and serum anti-Gal titer ≥1:50 were eligible for two intratumoral α-gal glycolipid injections given 4 weeks apart (cohort I: 0.1 mg/injection; cohort II: 1.0 mg/injection; cohort III: 10 mg/injection). Monitoring included blood for clinical, autoimmune, and immunological analyses and core tumor biopsies. Treatment outcome was determined 8 weeks after the first α-gal glycolipid injection. Nine pts received two intratumoral injections of α-gal glycolipids (3 pts/cohort). Injection-site toxicity was mild, and no systemic toxicity or autoimmunity could be attributed to the therapy. Two pts had stable disease by RECIST lasting 8 and 7 months. Tumor nodule biopsies revealed minimal to no change in inflammatory infiltrate between pre- and post-treatment biopsies except for 1 pt (cohort III) with a post-treatment inflammatory infiltrate. Two and four weeks post-injection, treated nodules in 5 of 9 pts exhibited tumor cell necrosis without neutrophilic or lymphocytic inflammatory response. Non-treated tumor nodules in 2 of 4 evaluable pts also showed necrosis. Repeated intratumoral injections of α-gal glycolipids are well tolerated, and tumor necrosis was seen in some tumor nodule biopsies after tumor injection with α-gal glycolipids.

The patient perspective of the diagnostic process for leprosy in Brazil. An exploratory study.

OBJECTIVES: To explore the patient experience of being diagnosed with leprosy and the support provided during this process in selected populations in Brazil. To understand the information needs of patients during diagnosis. To identify characteristics of patients with different diagnostic experiences. To add to the evidence base used for improving the diagnostic process for leprosy patients. DESIGN: A self-constructed questionnaire delivered to 116 participants, at three leprosy health centres, across three states in Brazil. RESULTS: Most participants felt under-informed during diagnosis; 68.1% wanted more information about leprosy. Nearly one-quarter of patients reported feeling unable to ask questions at diagnosis. Almost half of patients reported being worried about treatment, yet 43.3% reported not having the chance to talk about their concerns. Younger participants were significantly more likely to report feeling unable to ask questions and talk about their worries. The majority of participants (59.5%) reported not being given any written information to take away with them. 36.5% reported not being given advice about how to reduce the chance of other family members becoming ill with leprosy. Older males were most likely to be given this advice despite females being in most contact with family members in most cultures. CONCLUSIONS: It is recommended that patients are encouraged to ask questions and invited to talk about their concerns, particularly younger patients. It is recommended that a simple information leaflet be provided to all patients. These suggestions may require some financial input, more staff and longer consultations but should significantly improve the diagnostic process.

Evaluation of New Dihydrophthalazine-Appended 2,4-Diaminopyrimidines against Bacillus anthracis: Improved Syntheses Using a New Pincer Complex.

The synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat Bacillus anthracis is reported. An improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(II), allows the final Heck coupling to be performed at 90 °C using triethylamine as the base. These milder conditions have been used to achieve improved yields for new and previously reported substrates with functional groups that degrade or react at the normal 140 °C reaction temperature. An analytical protocol for separating the S and R enantiomers of two of the most active compounds is also disclosed. Finally, the X-ray structure for the most active enantiomer of the lead compound, (S)-RAB1, is given.

Synthesis and biological evaluation of 2,4-diaminopyrimidine-based antifolate drugs against Bacillus anthracis.

Due to the innate ability of bacteria to develop resistance to available antibiotics, there is a critical need to develop new agents to treat more resilient strains. As a continuation of our research in this area, we have synthesized a series of racemic 2,4-diaminopyrimidine-based drug candidates, and evaluated them against Bacillus anthracis. The structures are comprised of a 2,4-diaminopyrimidine ring, a 3,4-dimethoxybenzyl ring, and an N-acryloyl-substituted 1,2-dihydrophthalazine ring. Various changes were made at the C1 stereocenter of the dihydrophthalazine moiety in the structure, and the biological activity was assessed by measurement of the MIC and K(i) values to identify the most potent drug candidate.

Readiness: how prepared are you?

Disaster education is important for everyone and especially nurses. Being informed, making individual and family communication plans, and creating the needed supplies to shelter in place or evacuate for one's self and family are required core readiness behaviors. Nurses also need to understand their role within the employer's emergency plans and incident command structure. All of these behaviors help the nurse to be ready and available to care for patients during disaster and emergency incidents.

Registered nurses' perspectives on the new graduate working in the emergency department or critical care unit.

BACKGROUND: This qualitative study describes registered nurses' perspectives on work relationships with new graduates in emergency and critical care settings. METHODS: Six focus groups of registered nurses (N = 31) were interviewed in open and informal discussions lasting approximately 45 to 90 minutes. RESULTS: Two themes extracted from the data were lacking confidence and gaining acceptance into the unit's culture. Registered nurses were disillusioned by the lack of confidence, organization, and skill performance of the new graduate. They agreed that nurses "eat their young." CONCLUSION: Suggestions are offered for preceptors, mentors, and staff. Recommendations for supporting the new graduate in an uncivil environment are also given.

Nursing Students' Transfer of Learning During a Disaster Tabletop Exercise.

BACKGROUND: Disasters require nurses to make decisions. A tabletop exercise, used in disaster education, is a classroom activity for solving problems. PURPOSE: The study purposes were to (1) describe, as scores, the transfer of learning from basic medical-surgical coursework to student decisions made during a disaster scenario tabletop exercise and (2) identify students' attitudes about their use of their previous learning during this experience. METHOD: Researcher-designed instruments and a tabletop exercise were used to measure prelicensure students' transfer of select basic medical-surgical learning to their decisions during the exercise. RESULTS: Mean (SD) student scores during the tabletop exercise were as follows-Tabletop Matrix: infection, 17.61 (6.03); bleeding, 14.93 (5.36); pain, 11.17 (5.08); electrolyte, 13.73 (6.19); disaster knowledge: 19.46 (3.08); and attitudes: 51.41 (5.43). CONCLUSION: During this tabletop exercise, students demonstrated transfer of learning.

Nurses at the table: A naturalistic inquiry of nurses on governing boards.

In an environment in which there is little or no nursing presence on governing boards in healthcare organizations (HCOs), physicians, and nonclinicians take responsibility for keeping the other board members apprised of the quality of patient care, including nursing-generated, patient safety initiatives. Governing boards in HCOs are either not appointing nurses to governing boards or are not appointing nurses in numbers that are commensurate with the size and vital contributions of the profession. As a result, competent nursing professionals with an intimate understanding of quality care and patient safety are not in decision-making roles that may redesign health care and improve patient care. The purpose of this qualitative study was to describe experiences of nurse board members who hold governing board appointments in HCOs, and to describe the facilitators of and barriers to holding governing board appointments, as experienced by those nurse board members. This novel research employed naturalistic inquiry to explore the experiences of 12 nurse board members who held appointments with voting privileges in HCOs. From the interview data emerged four distinct themes: leveraging relationships and networking, valuing the mission of the board, feeling respected for my participation, and committing to board work. Facilitators of and barriers to governing board appointments were suggested. Findings validated the few previous research studies found in the literature and have implications for nursing leadership and governance.

The Tabletop Matrix: Determining Reliability for a Criterion-Referenced Performance Measure.

BACKGROUND: Disasters are high-impact events. Tabletop exercises are a historic education strategy used to determine policies, procedures, and strengths and challenges for those involved. A tabletop exercise was designed for students to demonstrate transfer of prior medical-surgical content to a novel context of a hospital patient surge following a disaster. To accompany the tabletop exercise, a tabletop matrix was developed as an instrument to measure students' learning transfer of medical-surgical content. METHOD: A pilot study was conducted with senior baccalaureate nursing students to determine instrument reliability and effectiveness of the tabletop exercise. RESULTS: Postpilot interrater reliability was established with medical-surgical experts for the matrix, scenarios, and dispositions. Cronbach's alpha could not be calculated, and rationale is provided. Improvements were made to the instrument's items. CONCLUSION: The tabletop matrix was determined to be a criterion-referenced performance measurement of nursing students' learning transfer of medical-surgical concepts to a novel circumstance using a disaster-scenario tabletop exercise. [J Nurs Educ. 2017;56(8):509-513.].

Changing Student Attitudes Toward Interprofessional Learning and Collaboration: Evidence for the Effectiveness of Partnering with Healthcare Mentors in the Academic Setting.

PURPOSE: Individuals living with chronic health conditions serving as healthcare mentors (HCM) allow the creation of high impact, authentic learning experiences. The purpose of this study was to examine the effectiveness of a 6-hour curricular experience involving HCM in changing student attitudes toward interprofessional learning (IPL) and collaboration (IPC). METHODS: Thirty-eight students from clinical psychology, nursing, physical therapy, and social work programs participated in either the learning intervention (n=19) or the control group (n=19). Students in the IPL group examined the HCMs, who were diagnosed with multiple sclerosis, shared the findings during an interprofessional team meeting, and collaboratively developed consensus-based interprofessional care recommendations. The Interdisciplinary Education Perception Scale, Readiness for Interprofessional Learning Scale, and Attitudes Toward Health Care Teams Scale were completed pre- and post-IPL. In addition, discipline-specific focus groups were also conducted. RESULTS: The IPL experience resulted in positive changes in student attitudes toward teamwork and collaboration. Teamwork among the students was reportedly characterized by open communication, mutual respect, and the incorporation of ideas from other disciplines. CONCLUSIONS: Positively changing students' attitudes and skills for IPC prior to licensure is an important first step in providing coordinated interprofessional care to patients/clients living with chronic health conditions.

Giving and receiving: a case study in service learning.

Service learning is becoming a requirement for many universities wanting to connect with the communities surrounding them while also instilling civic responsibility in their students. The process should benefit all involved. In the following case study, the authors describe their experience of initiating a service learning component in an introductory nursing course, from the design to the implementation of the project. Faculty concerns and student reactions are included.

Factors Contributing to the Delay in Diagnosis and Continued Transmission of Leprosy in Brazil--An Explorative, Quantitative, Questionnaire Based Study.

BACKGROUND: Leprosy is a leading cause of preventable disability worldwide. Delay in diagnosis of patients augments the transmission of infection, and allows progression of disease and more severe disability. Delays in diagnosis greater than ten years have been reported in Brazil. To reduce this delay, it is important to identify factors that hinder patients from presenting to doctors, and those that delay doctors from diagnosing patients once they have presented. This study aimed to explore factors associated with the delayed diagnosis of leprosy in Brazil. METHODOLOGY/ PRINCIPAL FINDINGS: This is an exploratory study using a self-constructed questionnaire delivered to patients attending three leprosy referral clinics across three states in Brazil. Data were analysed to determine associations between variables and the time taken for participants to present to the health-service, and between variables and the time taken for doctors to diagnose participants once they had presented. Participants who suspected they had leprosy but feared community isolation were 10 times more likely to wait longer before consulting a doctor for their symptoms (OR 10.37, 95% CI 2.18-49.45, p = 0.003). Participants who thought their symptoms were not serious had a threefold greater chance of waiting longer before consulting than those who did (OR 3.114, 95% CI 1.235-7.856, p = 0.016). Forty-two point six per cent of participants reported initially receiving a diagnosis besides leprosy. These had a three times greater chance of receiving a later diagnosis of leprosy compared to those not misdiagnosed or not given a diagnosis (OR 2.867, 95% CI 1.288-6.384, p = 0.010). CONCLUSIONS/ SIGNIFICANCE: This study implies a need for patient education regarding leprosy symptoms and the reduction of stigma to encourage patients to present. The high rate of misdiagnosis reported suggests a need to increase clinician suspicion of leprosy. Further education regarding disease symptoms in medical school curriculums may be advisable.

Microwave ablation of hepatic tumors using dual-loop probes: results of a phase I clinical trial.

Hepatic tumors are a common cause of death worldwide. However, few patients are candidates for resection at the time of presentation. Microwave ablation is a viable alternative available for these patients. To date, only straight antennas are used for microwave ablation. Recently, a prototype loop-shaped microwave antenna was developed that, in animal studies, more effectively kills tumors. For this study, the dual-probe lesions were created by placing the probes in both tumors and normal livers. Lesions were created with 60 watts applied power for 5-7 minutes. The livers were sectioned and stained for viability. The average ablation volume was 63.9 +/- 8.7 cm(3). Microwave ablation with the loop probes results in complete tumor kill at the ablation/tumor interface, and adjacent to surrounding blood vessels. In addition, vessels within the ablation/tumor interface failed to show viable cells. The shape of the lesions was not distorted by proximity to blood vessels. The advantages of this configuration over conventional straight probes include the ability to encircle a tumor, deliver large amounts of precisely targeted microwave energy to the tumor, and spare normal liver outside the loop.

Cooperative learning and case study: does the combination improve students' perception of problem-solving and decision making skills?

The purpose of this study was to investigate the effectiveness of cooperative learning techniques combined with case study on nursing students' self-perception of problem-solving and decision making skills in comparison with other teaching-learning methods. A quasi-experimental pre-test to post-test static group comparison design was used to determine the influence of the different teaching methodologies. Three associate degree colleges provided a convenience sample of nursing students (N=123). An experimental group (n=31) was taught through cooperative learning and case study. One comparison group, was taught through lecture and large group case study (n=46) and another comparison group was taught through lecture only (n=24). A third comparison group taught through lecture and occasional use of non-cooperative learning groups using continuing case study (n=22) was used as a post-test only control group. No two groups were significantly different at the 0.5 level. The results, however, showed that the experimental group obtained scores indicating somewhat better self-perception of both problem-solving and decision making skills.

Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis.

Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC) to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC which metastasized to the base of his penis within 1 month of symptom onset. We also discuss the possible route of metastasis based on primary tumor size and location within the retroperitoneum.

Practicing the art of nursing through student-designed continuing case study and cooperative learning.

Theorists over the years have debated the art versus the science of nursing, keeping each form distinct and separate from the other. The author presents a way for students to learn the art of nursing through a scientific rational approach of student-designed continuing case study and cooperative learning.