Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells.

The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals.

CD1a on Langerhans cells controls inflammatory skin disease.

CD1a is a lipid-presenting molecule that is abundantly expressed on Langerhans cells. However, the in vivo role of CD1a has remained unclear, principally because CD1a is lacking in mice. Through the use of mice with transgenic expression of CD1a, we found that the plant-derived lipid urushiol triggered CD1a-dependent skin inflammation driven by CD4(+) helper T cells that produced the cytokines IL-17 and IL-22 (TH17 cells). Human subjects with poison-ivy dermatitis had a similar cytokine signature following CD1a-mediated recognition of urushiol. Among various urushiol congeners, we identified diunsaturated pentadecylcatechol (C15:2) as the dominant antigen for CD1a-restricted T cells. We determined the crystal structure of the CD1a-urushiol (C15:2) complex, demonstrating the molecular basis of urushiol interaction with the antigen-binding cleft of CD1a. In a mouse model and in patients with psoriasis, CD1a amplified inflammatory responses that were mediated by TH17 cells that reacted to self lipid antigens. Treatment with blocking antibodies to CD1a alleviated skin inflammation. Thus, we propose CD1a as a potential therapeutic target in inflammatory skin diseases.

Examining moral injury in clinical practice: A narrative literature review.

Healthcare workers experience moral injury (MI), a violation of their moral code due to circumstances beyond their control. MI threatens the healthcare workforce in all settings and leads to medical errors, depression/anxiety, and personal and occupational dysfunction, significantly affecting job satisfaction and retention. This article aims to differentiate concepts and define causes surrounding MI in healthcare. A narrative literature review was performed using SCOPUS, CINAHL, and PubMed for peer-reviewed journal articles published in English between 2017 and 2023. Search terms included "moral injury" and "moral distress," identifying 249 records. While individual risk factors predispose healthcare workers to MI, root causes stem from healthcare systems. Accumulation of moral stressors and potentially morally injurious events (PMIEs) (from administrative burden, institutional betrayal, lack of autonomy, corporatization of healthcare, and inadequate resources) result in MI. Individuals with MI develop moral resilience or residue, leading to burnout, job abandonment, and post-traumatic stress. Healthcare institutions should focus on administrative and climate interventions to prevent and address MI. Management should ensure autonomy, provide tangible support, reduce administrative burden, advocate for diversity of clinical healthcare roles in positions of interdisciplinary leadership, and communicate effectively. Strategies also exist for individuals to increase moral resilience, reducing the impact of moral stressors and PMIEs.

Investigation of SARS-CoV-2 Transmission Associated With a Large Indoor Convention - New York City, November-December 2021.

During November 19-21, 2021, an indoor convention (event) in New York City (NYC), was attended by approximately 53,000 persons from 52 U.S. jurisdictions and 30 foreign countries. In-person registration for the event began on November 18, 2021. The venue was equipped with high efficiency particulate air (HEPA) filtration, and attendees were required to wear a mask indoors and have documented receipt of at least 1 dose of a COVID-19 vaccine.* On December 2, 2021, the Minnesota Department of Health reported the first case of community-acquired COVID-19 in the United States caused by the SARS-CoV-2 B.1.1.529 (Omicron) variant in a person who had attended the event (1). CDC collaborated with state and local health departments to assess event-associated COVID-19 cases and potential exposures among U.S.-based attendees using data from COVID-19 surveillance systems and an anonymous online attendee survey. Among 34,541 attendees with available contact information, surveillance data identified test results for 4,560, including 119 (2.6%) persons from 16 jurisdictions with positive SARS-CoV-2 test results. Most (4,041 [95.2%]), survey respondents reported always wearing a mask while indoors at the event. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 minutes. Among 4,560 attendees who received testing, evidence of widespread transmission during the event was not identified. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and the Omicron variant (BA.1 sublineage) in five (25%) cases. These findings reinforce the importance of implementing multiple, simultaneous prevention measures, such as ensuring up-to-date vaccination, mask use, physical distancing, and improved ventilation in limiting SARS-CoV-2 transmission, during large, indoor events.†.

Strategies for Providing Culturally Sensitive Care to Diverse Populations.

ABSTRACT: Nurses are called to care for patients and families from many backgrounds and cultural groups. This article discusses the key strategies of cultural humility, conscientious practice, and establishing trust that promotes cultural sensitivity as well as congruence with Christian values. When implemented, these strategies can facilitate the provision of quality, culturally sensitive patient care that conforms to a biblical worldview.

Living up to the job: Confessions of a Brigadier General on the lived experiences of becoming a leader in the Air Force Nurse Corps.

Today, nurse leadership positions are more and more common. However, there have been many exemplary Nurse Leaders in the past whose contributions and sacrifices enabled nursing to transform to the leadership position it is today but have not been documented. It is important to recover and record this history so that future generations of nurses can learn from past examples in a way they cannot learn with current nursing education alone. This article examines the development of the professional nurse through the lens of the service of Brigadier General Sue Ellen Turner. The oral history method guided the exploration of memories and experiences. The recurring characteristics of discernment, reflection, and ability to break barriers/build relationships contributed most to the general's success in restructuring organizational systems to optimize leadership opportunities for nurses. The conclusion discusses the lasting impact and future implications of Turner's work on the profession of nursing.

Air Force Nursing Executive leadership impact on health care 2004-2008.

Recorded history allows us to recognize our past and can contribute to the present and future nursing practice. The purpose of this study is to examine the impact of the United States Air Force Nursing Executive leadership on military health care transformation, through Major General (Retired) Melissa A. Rank's personal stories and experiences. This study explores the development and impact of Air Force nursing in its historical, social, and global context between the years of 2004-2008. The oral history method was used to explore and record the professional life experiences of a great military nurse leader. The United States Air Force Nurse Corps has contributed to global healthcare via humanitarian medical support, medical disaster relief, aeromedical patient transport, development of best practices, advances in technology, education programs, and transformation in deployed medical care during times of war, peace, and natural disasters.

Screening for Child Sexual Exploitation in Online Sexual Health Services: An Exploratory Study of Expert Views.

BACKGROUND: Sexual health services routinely screen for child sexual exploitation (CSE). Although sexual health services are increasingly provided online, there has been no research on the translation of the safeguarding function to online services. We studied expert practitioner views on safeguarding in this context. OBJECTIVE: The aim was to document expert practitioner views on safeguarding in the context of an online sexual health service. METHODS: We conducted semistructured interviews with lead professionals purposively sampled from local, regional, or national organizations with a direct influence over CSE protocols, child protection policies, and sexual health services. Interviews were analyzed by three researchers using a matrix-based analytic method. RESULTS: Our respondents described two different approaches to safeguarding. The "information-providing" approach considers that young people experiencing CSE will ask for help when they are ready from someone they trust. The primary function of the service is to provide information, provoke reflection, generate trust, and respond reliably to disclosure. The approach values online services as an anonymous space to test out disclosure without commitment. The "information-gathering" approach considers that young people may withhold information about exploitation. Therefore, services should seek out information to assess risk and initiate disclosure. This approach values face-to-face opportunities for individualized questioning and immediate referral. CONCLUSIONS: The information-providing approach is associated with confidential telephone support lines and the information-gathering approach with clinical services. The approach adopted online will depend on ethos and the range of services provided. Effective transition from online to clinic services after disclosure is an essential element of this process and further research is needed to understand and support this transition.

Enhanced molecular mobility of ordinarily structured regions drives polyglutamine disease.

Polyglutamine expansion is a hallmark of nine neurodegenerative diseases, with protein aggregation intrinsically linked to disease progression. Although polyglutamine expansion accelerates protein aggregation, the misfolding process is frequently instigated by flanking domains. For example, polyglutamine expansion in ataxin-3 allosterically triggers the aggregation of the catalytic Josephin domain. The molecular mechanism that underpins this allosteric aggregation trigger remains to be determined. Here, we establish that polyglutamine expansion increases the molecular mobility of two juxtaposed helices critical to ataxin-3 deubiquitinase activity. Within one of these helices, we identified a highly amyloidogenic sequence motif that instigates aggregation and forms the core of the growing fibril. Critically, by mutating residues within this key region, we decrease local structural fluctuations to slow ataxin-3 aggregation. This provides significant insight, down to the molecular level, into how polyglutamine expansion drives aggregation and explains the positive correlation between polyglutamine tract length, protein aggregation, and disease severity.

Oxidation of an exposed methionine instigates the aggregation of glyceraldehyde-3-phosphate dehydrogenase.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous and abundant protein that participates in cellular energy production. GAPDH normally exists in a soluble form; however, following necrosis, GAPDH and numerous other intracellular proteins convert into an insoluble disulfide-cross-linked state via the process of "nucleocytoplasmic coagulation." Here, free radical-induced aggregation of GAPDH was studied as an in vitro model of nucleocytoplasmic coagulation. Despite the fact that disulfide cross-linking is a prominent feature of GAPDH aggregation, our data show that it is not a primary rate-determining step. To identify the true instigating event of GAPDH misfolding, we mapped the post-translational modifications that arise during its aggregation. Solvent accessibility and energy calculations of the mapped modifications within the context of the high resolution native GAPDH structure suggested that oxidation of methionine 46 may instigate aggregation. We confirmed this by mutating methionine 46 to leucine, which rendered GAPDH highly resistant to free radical-induced aggregation. Molecular dynamics simulations suggest that oxidation of methionine 46 triggers a local increase in the conformational plasticity of GAPDH that likely promotes further oxidation and eventual aggregation. Hence, methionine 46 represents a "linchpin" whereby its oxidation is a primary event permissive for the subsequent misfolding, aggregation, and disulfide cross-linking of GAPDH. A critical role for linchpin residues in nucleocytoplasmic coagulation and other forms of free radical-induced protein misfolding should now be investigated. Furthermore, because disulfide-cross-linked aggregates of GAPDH arise in many disorders and because methionine 46 is irrelevant to native GAPDH function, mutation of methionine 46 in models of disease should allow the unequivocal assessment of whether GAPDH aggregation influences disease progression.

Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial.

BACKGROUND: Malignant pleural mesothelioma incidence continues to rise, with few available evidence-based therapeutic options. Results of previous non-randomised studies suggested that video-assisted thoracoscopic partial pleurectomy (VAT-PP) might improve symptom control and survival. We aimed to compare efficacy in terms of overall survival, and cost, of VAT-PP and talc pleurodesis in patients with malignant pleural mesothelioma. METHODS: We undertook an open-label, parallel-group, randomised, controlled trial in patients aged 18 years or older with any subtype of confirmed or suspected mesothelioma with pleural effusion, recruited from 12 hospitals in the UK. Eligible patients were randomly assigned (1:1) to either VAT-PP or talc pleurodesis by computer-generated random numbers, stratified by European Organisation for Research and Treatment of Cancer risk category (high vs low). The primary outcome was overall survival at 1 year, analysed by intention to treat (all patients randomly assigned to a treatment group with a final diagnosis of mesothelioma). This trial is registered with ClinicalTrials.gov, number NCT00821860. FINDINGS: Between Oct 24, 2003, and Jan 24, 2012, we randomly assigned 196 patients, of whom 175 (88 assigned to talc pleurodesis, 87 assigned to VAT-PP) had confirmed mesothelioma. Overall survival at 1 year was 52% (95% CI 41-62) in the VAT-PP group and 57% (46-66) in the talc pleurodesis group (hazard ratio 1·04 [95% CI 0·76-1·42]; p=0·81). Surgical complications were significantly more common after VAT-PP than after talc pleurodesis, occurring in 24 (31%) of 78 patients who completed VAT-PP versus ten (14%) of 73 patients who completed talc pleurodesis (p=0·019), as were respiratory complications (19 [24%] vs 11 [15%]; p=0·22) and air-leak beyond 10 days (five [6%] vs one [1%]; p=0·21), although not significantly so. Median hospital stay was longer at 7 days (IQR 5-11) in patients who received VAT-PP compared with 3 days (2-5) for those who received talc pleurodesis (p<0·0001). INTERPRETATION: VAT-PP is not recommended to improve overall survival in patients with pleural effusion due to malignant pleural mesothelioma, and talc pleurodesis might be preferable considering the fewer complications and shorter hospital stay associated with this treatment. FUNDING: BUPA Foundation.

Cost effectiveness of endosonography versus surgical staging in potentially resectable lung cancer: a health economics analysis of the ASTER trial from a European perspective.

In the ASTER study, mediastinal staging was more accurate for patients randomised to combined endobronchial and endoscopic ultrasound, followed by surgical staging if endoscopy was negative, versus surgical staging alone. Here, we report survival, quality of life and cost effectiveness up to 6 months, for the UK, The Netherlands and Belgium, separately. Survival in the two arms of the study was similar. In all three countries, the endosonography strategy had slightly higher quality-adjusted life years over 6 months, and was cheaper. Therefore, based on clinical accuracy and cost effectiveness, we conclude that mediastinal staging should commence with endosonography.

Caring: The heart of online nursing education- An integrative review.

With the widespread adoption of online education, nursing educators have observed significant challenges related to learner engagement and participation. Over the past decade, the implementation of Caring has consistently displayed a beneficial influence on creating and maintaining a sustainable online learning environment. However, existing online nursing curricula often lack a Caring and learner-centered approach. The aim of this integrative review is to analyze existing research and gain a comprehensive understanding of the factors that promote a sense of Caring in online nursing education programs. A systematic search for published peer reviewed, English language literature identifying the factors that contribute to Caring in online nursing education was conducted utilizing five databases. Findings from 18 included articles suggest that a combination of Caring strategies implemented by faculty and students, and the utilization of institutional resources contribute to enhanced student outcomes. Faculty driven strategies that promote an online Caring environment are Caring communication, role modeling, building personal connections, demonstrating teaching passion, and embodying emotional intelligence. Student behaviors that promote a Caring online environment include deliberate commitment to learning, genuine presence, active listening, and meaningful interactions with peers. Furthermore, incorporating instructional design to develop a Caring learning platform provides synergy to the student and faculty strategies to produce a Caring environment.

Resilience and Ethics in Nursing Education and Practice: Needs and Opportunities.

BACKGROUND: Nursing faculty and clinicians are leaving the profession due to increased workload and burnout. Evidence-based interventions to build skills in resilience and well-being are encouraged; however, strategies to implement them in nursing curricula and nurse residency programs (NRPs) are not well known. PURPOSE: To understand the current state of resilience, well-being, and ethics content in the curriculum in schools of nursing and NRPs in the state of Maryland as part of a statewide initiative for Renewal, Resilience and Retention of Maryland Nurses (R 3 ). METHODS: A descriptive survey was distributed to leaders of all Maryland nursing schools and NRP directors. RESULTS: Respondents (n = 67) reported minimal resilience, well-being, and ethics content. Teaching modalities included lecture, journaling, mindfulness, and the code of ethics. Barriers included lack of faculty knowledge, low priority, time constraints, and limited resources. CONCLUSION: Resilience, well-being, and ethics content is limited in nursing curricula. Developing educator skills and best practices to foster resilience and ethical practice are needed.

A qualitative descriptive study of effective leadership and leadership development strategies used by nurse leaders in European island countries.

AIM: Nurse leaders influence workplace culture; however, little is known about ethnic cultural influences on nurse leader development. This research aims to identify personal strategies promoting effective leadership by nurse leaders from European small island countries. DESIGN: Descriptive qualitative study. METHODS: In 2017, nineteen semi-structured interviews with nurse leaders from England, Greece, Republic of Ireland and Malta explored leadership journeys, strategies employed to support their growth and development, and how cultural identity played a role. Transcripts were analysed using reflexive thematic analysis. RESULTS: Four main themes and 12 subthemes captured the strategies and approaches of the nurse leaders: (1) Influences, (2) Communication, (3) Process and (4) Relationships. These findings reflect and validate the five transformational leadership practices of the Exemplary Leadership Model. While cultural island identity was discussed, there was a shared cultural identity within the role of "nurse leader" that spanned all islands. PATIENT OR PUBLIC CONTRIBUTIONS: Nineteen nurse leaders contributed to this study.

Travel history among persons infected with SARS-CoV-2 variants of concern in the United States, December 2020-February 2021.

The first three SARS-CoV-2 phylogenetic lineages classified as variants of concern (VOCs) in the United States (U.S.) from December 15, 2020 to February 28, 2021, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1) lineages, were initially detected internationally. This investigation examined available travel history of coronavirus disease 2019 (COVID-19) cases reported in the U.S. in whom laboratory testing showed one of these initial VOCs. Travel history, demographics, and health outcomes for a convenience sample of persons infected with a SARS-CoV-2 VOC from December 15, 2020 through February 28, 2021 were provided by 35 state and city health departments, and proportion reporting travel was calculated. Of 1,761 confirmed VOC cases analyzed, 1,368 had available data on travel history. Of those with data on travel history, 1,168 (85%) reported no travel preceding laboratory confirmation of SARS-CoV-2 and only 105 (8%) reported international travel during the 30 days preceding a positive SARS-CoV-2 test or symptom onset. International travel was reported by 92/1,304 (7%) of persons infected with the Alpha variant, 7/55 (22%) with Beta, and 5/9 (56%) with Gamma. Of the first three SARS-CoV-2 lineages designated as VOCs in the U.S., international travel was common only among the few Gamma cases. Most persons infected with Alpha and Beta variant reported no travel history, therefore, community transmission of these VOCs was likely common in the U.S. by March 2021. These findings underscore the importance of global surveillance using whole genome sequencing to detect and inform mitigation strategies for emerging SARS-CoV-2 VOCs.

Partnering industry to develop clinical information systems.

Over the past six months, the nursing team from the Department of Health's Informatics Directorate has been working with colleagues in industry to promote and share learning and understanding of issues surrounding the nursing profession. Team members were asked among other things to identify key questions senior nursing colleagues and suppliers should ask one another when considering the implementation of a new system for recording clinical information and extracting pertinent data. This article aims to encourage collaborative working and understanding of the importance of senior nurse involvement in choosing and delivering the right system for staff and patients.

Developing Resilience: Strategies to Adapt Within an Interprofessional Team.

Resilience can be defined as sustaining well-being in the face of adversity by harnessing internal and/or external resources. Many of the strategies that promote highly effective teams, such as regulating emotions, self-reflection, and inclusion, may also contribute to team resilience. Nurse leaders can facilitate social connections, optimism, self-care, mindfulness practices, and meaningful recognition as strategies to promote nurse resilience. Resilience may mitigate many of the harmful effects for nurses working in the high demanding health care work environment.

Gastric perforation after blunt abdominal trauma: first case report in Argentina.

We report the case of a 18-year-old male with gastric perforation due to blunt abdominal trauma as a result of a vehicular collision. An exploratory laparotomy with suturing of the lesion and an omental patch is performed. The post-operative outcome was favorable. Traumatic injury is a frequent cause of hospital admission to the emergency department in Argentina, and vehicle collisions are the first cause of death and permanent disability in young adults. Isolated gastric perforations following blunt abdominal are an uncommon finding, and there are only a few published cases in the literature. It is interesting to discuss the type of surgical approach.

Acute appendicitis secondary to metastatic breast cancer. 12 Years after first primary tumor diagnosis. A case report.

INTRODUCTION: Metastatic adenocarcinoma to the appendix is an uncommon finding, there are few published cases in the literature of appendicitis from metastatic breast carcinoma. PRESENTATION OF CASE: A 51-year-old female was admitted to the emergency department with a presumptive diagnosis of acute appendicitis with a past medical history of stage IV Breast Cancer 12 years ago. Appendectomy was performed, finding a perforated appendix. Anatomo-pathology examination revealed a semi-differentiated carcinoma involving the tip of the appendix. DISCUSSION: Gastrointestinal tract (GIT) metastases of breast carcinoma are an uncommon finding. Appendiceal metastases are a very uncommon finding, and the interval between diagnosis of the primary carcinoma and the metastases can be many years. There are no reports about whether right hemicolectomy provides better oncological outcomes than an appendectomy in stage IV BC. CONCLUSION: There are no guidelines for the management of this disease but unquestionably, multidisciplinary management leads to better outcomes.