One ring doesn't rule them all: Distinct nuclear pore complexes in a single cell.

Determining the structural plasticity and dynamics of nuclear pore complexes (NPCs) are major challenges. In this issue of Cell, Akey et al. present comprehensive NPC structures from in vitro and in vivo preparations, demonstrating multiple NPC forms in single cells while providing insight into the evolutionary origin of NPC architecture.

Codesign and Launch of 'On the Ball': An Inclusive Community-Based 'Testicular Awareness' Campaign.

INTRODUCTION: Increased awareness of testicular diseases can lead to early diagnosis. Evidence suggests that men's awareness of testicular diseases is low, with many expressing their willingness to delay help-seeking for symptoms of concern. The risk of testicular diseases is higher in gender and sexual minority groups. In this study, we discuss the codesign, refinement and launch of 'On the Ball', an inclusive community-based 'testicular awareness' campaign. METHODS: The World Café participatory research methodology was used. Individuals from Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, policymakers, media/marketing experts and graphic designers were recruited. Participants were handed a brief for 'On the Ball', which was designed based on feedback from a previous World Café workshop. They were assigned to three tables. Participants rotated tables at random for three 20-min rounds of conversations. Each table had a facilitator who focussed on one element of the campaign brief. Data were collected using audio recorders and in writing and were analysed thematically. RESULTS: Thirteen individuals participated in the workshop. The following themes emerged from the data: (i) campaign identity, (ii) campaign delivery and (iii) campaign impact. Participants recommended enhancements to the campaign logo, slogan, social media posts and poster. They suggested delivering the campaign online via social media and offline using various print and broadcast media. Participants recommended targeting areas with a large number of men such as workplaces. To help measure the impact of the campaign, participants proposed capturing social media analytics and tracking statistics relating to testicular diseases. Recommendations were used to refine the 'On the Ball' campaign and launch it in a university. In total, 411 students engaged with the various elements of the campaign during the soft launch. CONCLUSIONS: 'On the Ball' campaign visuals ought to be inclusive. Online and offline campaign delivery is warranted to reach out to a wider cohort. Campaign impact can be captured using social media analytics as well as measuring clinical outcomes relating to testicular diseases. Future research is needed to implement the campaign online and offline, explore its impact and evaluate its feasibility, acceptability, cost and effect on promoting testicular awareness. PATIENT OR PUBLIC CONTRIBUTION: The 'On the Ball' campaign was codesigned and refined with members of Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, health policymakers, media and marketing experts and graphic designers using the World Café participatory research methodology.

Supportive care interventions for men with urological cancers: a scoping review.

PURPOSE: To identify supportive care interventions for men with urological cancers. METHODS: Experimental studies conducted among men with any urological cancer were eligible for inclusion. Academic Search Complete, CINAHL Plus with Full Text, MEDLINE, APA PsycArticles, APA PsycInfo, Social Sciences Full Text (H.W. Wilson), SocINDEX with Full Text, ERIC, Google Scholar and ClinicalTrials.gov were searched on 6 December 2022. No database limits were applied. The included studies were methodologically appraised. A narrative synthesis of the results was conducted. RESULTS: Thirty studies were included with 10 categories of interventions identified. Over 300 outcomes were measured, and more than 100 instruments were used. Multicomponent interventions generally led to positive changes in physiological outcomes like body mass index, as well as exercise tolerance and quality of life. This change, however, was not sustained in the long term. Cognitive-behavioural interventions significantly improved psychological symptoms but seldom physical symptoms. Telephone and web-based interventions showed great promise in improving outcomes like depression, positive affect, negative affect, perceived stress, spiritual wellbeing and fatigue. Findings from physical activity/exercise-based interventions were promising for both, physical and psychological outcomes. Rehabilitative interventions were associated with significant improvements in quality of life, urinary symptoms and psychological symptoms, albeit in the short term. Mixed results were reported for nurse-led interventions, family-based interventions and nutritional interventions. CONCLUSION: All but one study focused exclusively on prostate cancer. The included studies were significantly heterogeneous. Multicomponent, cognitive-behavioural, telephone and web-based, physical activity/exercise-based and rehabilitative interventions showed great promise in improving various outcomes. This improvement, however, was often short-lived.

Views of voluntary, temporary out-of-home firearm storage among individuals living in a firearm-owning home: results from a qualitative study in two states.

INTRODUCTION: Firearms account for the majority of suicide deaths in the USA. A recommended approach for suicide prevention is reducing access to firearms by temporarily removing them from the home. We sought to understand how firearm owners and those who reside with them view and might use voluntary, temporary out-of-home firearm storage. METHODS: From July to November 2021, we interviewed English-speaking adults in Colorado and Washington who own firearms or reside with them, using semistructured interviews. We used a team-based mixed deductive and inductive approach to code transcripts and identify themes. RESULTS: Half of the 38 interviewees were men (53%) aged 35-54 years (40%); 92% identified as white. The average age that participants reported first having a firearm was 20.4 years; 16% reported never owning a firearm themselves, only living in homes with firearms. Qualitative findings fell into broad themes: (1) storage with family members/friends, (2) concerns/challenges with storing a firearm with a business/organization, (3) importance of trust (4) outreach methods for out-of-home storage programmes. CONCLUSION: Programmes for voluntary, temporary out-of-home firearm storage will not be impactful unless such storage is desired and used. Understanding views of potential storage users can help support development of acceptable and feasible programmes.

Promoting 'testicular awareness': Co-design of an inclusive campaign using the World Café Methodology.

INTRODUCTION: Testicular cancer is the most common cancer in men aged 15-44 years in many countries. Most men with testicular cancer present with a lump. Testicular symptoms are more likely to occur secondary to benign diseases like epididymo-orchitis, a common sexually transmitted infection. Gender and sexual minorities are at an increased risk of testicular diseases and health disparities. The aim of this study was to co-design an inclusive community-based campaign to promote testicular awareness. METHODS: This study uses the World Café methodology. Participation was sought from Lesbian, Gay, Bisexual, Transgender and Queer+ friendly organisations, testicular cancer survivors, health policy makers, media and marketing experts and graphic designers. Participants engaged in three rounds of conversations to co-design the campaign. Data were collected using drawing sheets, artefact cards, sticky notes, coloured markers and a voice recorder. Deductive thematic analysis was conducted. RESULTS: Seventeen individuals participated in the study. Six themes emerged from the analysis as follows: (i) online communication; (ii) offline communication; (iii) behavioural targeting and education; (iv) campaign frequency and reach; (v) demographic segmentation; and (vi) campaign identity. The use of social media for campaign delivery featured strongly in all conversations. Participants also recommended offline communication using posters and radio/television advertisements to scale up the campaign and achieve wider reach. Advertisements to overcome embarrassment surrounding testicular health were particularly recommended. Participants emphasised that campaign delivery must be dynamic whilst ensuring that the health-promoting messages are not diluted or lost. They stressed the importance of being inclusive and tailoring the campaign to different age groups, gender identities and sexual orientations. CONCLUSIONS: Study recommendations will be used to design and deliver the campaign. Future research will be needed to evaluate the feasibility, acceptability, cost and effect of the campaign on promoting testicular awareness and early detection of testicular diseases. PATIENT OR PUBLIC CONTRIBUTION: A participatory research approach was used to co-design the campaign with members of Lesbian, Gay, Bisexual, Transgender and Queer+ (LGBTQ+) friendly organisations, LGBTQ+ student bodies, LGBTQ+ staff networks, LGBTQ+ sports clubs, men's health organisations, testicular cancer survivors, health policy makers, media and marketing experts and graphic designers.

Virtual Reality Simulation in Nursing and Midwifery Education: A Usability Study.

Virtual reality simulation offers students the opportunity to acquire clinical and psychomotor skills in a safe and interactive environment. This study describes the usability of virtual reality simulation among undergraduate nursing and midwifery students. Participants were recruited using convenience and snowball sampling and engaged in a 20-minute virtual reality simulation scenario of their choice. They then completed a 21-item survey comprising a sociodemographic questionnaire, the System Usability Scale, a satisfaction questionnaire, and open-ended questions. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed using deductive content analysis. Forty-three students participated in this study. The mean (SD) System Usability Scale score was 75.87 (13.7), indicating that virtual reality simulation was acceptable. Almost all participants were either "extremely satisfied" or "somewhat satisfied" with virtual reality simulation, which was perceived as informative and enjoyable, fostering safe and self-directed learning without causing patient harm. Participants recommended using virtual reality simulation to practice clinical skills, prepare for clinical placements, and learn about rare clinical situations. Virtual reality simulation needs to be underpinned by a strong pedagogy and aligned with learning outcomes. Educators and students should be trained in virtual reality simulation prior to its integration into the curriculum.

Extreme Risk Protection Orders in Older Adults in Six U.S. States: A Descriptive Study.

OBJECTIVES: Extreme Risk Protection Orders (ERPOs) allow a court to restrict firearm access for individuals ("respondents") at imminent risk of harm to self/others. Little is known about ERPOs use for older adults, a population with higher rates of suicide and dementia. METHODS: We abstracted ERPO cases through June 30, 2020, from California, Colorado, Connecticut, Florida, Maryland, and Washington. We restricted our analysis to petitions for older (≥65 years) respondents, stratified by documented cognitive impairment. RESULTS: Among 6,699 ERPO petitions, 672 (10.0%) were for older adults; 13.7% (n = 92) of these noted cognitive impairment. Most were white (75.7%) men (90.2%). Cognitively impaired (vs. non-impaired) respondents were older (mean age 78.2 vs 72.7 years) and more likely to have documented irrational/erratic behavior (30.4% vs 15.7%), but less likely to have documented suicidality (33.7% vs 55.0%). At the time of the petition, 56.2% of older adult respondents had documented firearm access (median accessible firearms = 3, range 1-160). CONCLUSIONS: Approximately 14% of ERPO petitions for older adults involved cognitive impairment; one-third of these noted suicide risk. Studies examining ERPO implementation across states may inform usage and awareness. CLINICAL IMPLICATIONS: ERPOs may reduce firearm access among older adults with cognitive impairment, suicidality, or risk of violence.

Voluntary, temporary out-of-home firearm storage: A survey of firearm retailers and ranges in two states.

Out-of-home storage of personal firearms is one recommended option for individuals at risk of suicide, and statewide online maps of storage locations have been created in multiple states, including Colorado and Washington. We sought to examine both the extent to which firearm retailers and ranges offer temporary, voluntary firearm storage and the perceived barriers to providing this service. We invited all firearm retailers and ranges in Colorado and Washington to complete an online or mailed survey; eligible sites had to have a physical location where they could provide storage. Between June-July 2021, 137 retailers/ranges completed the survey (response rate = 25.1%). Nearly half (44.5%) of responding firearm retailers/ranges in Colorado and Washington State indicated they had ever provided firearm storage. Among those who had ever offered storage, 80.3% currently offered storage while 19.7% no longer did. The majority (68.6%) of participants had not heard of the Colorado/Washington gun storage maps and 82.5% did not believe they were currently listed on the maps. Respondents indicated liability waivers would most influence their decision about whether to start or continue providing temporary, voluntary storage of firearms. Understanding current practices, barriers, and concerns about providing out-of-home storage by retailers and ranges may support development of more feasible approaches for out-of-home firearm storage during times of suicide risk.

A Qualitative study on diverse perspectives and identities of firearm owners.

OBJECTIVE: Research surrounding firearm ownership is often contextualised within the perspectives of older white men. We expand this description using the perceptions of a diverse group of firearm-owning stakeholders. METHODS: We conducted semistructured interviews from October 2020 to May 2021 with Colorado/Washington State stakeholders representing (1) firearm ranges/retailers; (2) law enforcement agencies or (3) relevant state/national firearm organisations. Data were analysed using standard qualitative techniques and included 25 participants, representing varied sociocultural groups including racial and ethnic minorities, political minorities and sexual minorities. RESULTS: Participants for this analysis were of different self-identified sociocultural groups including racial and ethnic minorities (African American, Hispanic and Asian), political minorities (liberal) and sexual minorities, defined as Lesbian, Gay, Bisexual, and Transgender (LGBT). Perspectives on firearm ownership included an idea of gun culture as a component of (1) personal identity, (2) an expression of full citizenship and (3) necessary for self-protection. A strong subtheme was the intersection of minority group and firearm owner identities, creating a need for divergent social communities because of ideas on traditional gun culture. These communities are a safe place for individuals belonging to minority groups to escape negative external and internal group associations with firearms. CONCLUSION: Perspectives on firearms and firearm ownership in the secondary analysis were heterogeneous and related to personal experiences, external and internal group pressures that influence individual behaviour. Understanding the breadth of perspectives on firearm ownership is imperative to engaging individuals for risk reduction. This study adds to the literature by expanding an understanding of the motivation for firearm ownership among diverse communities.

Climate shapes and shifts functional biodiversity in forests worldwide.

Much ecological research aims to explain how climate impacts biodiversity and ecosystem-level processes through functional traits that link environment with individual performance. However, the specific climatic drivers of functional diversity across space and time remain unclear due largely to limitations in the availability of paired trait and climate data. We compile and analyze a global forest dataset using a method based on abundance-weighted trait moments to assess how climate influences the shapes of whole-community trait distributions. Our approach combines abundance-weighted metrics with diverse climate factors to produce a comprehensive catalog of trait-climate relationships that differ dramatically-27% of significant results change in sign and 71% disagree on sign, significance, or both-from traditional species-weighted methods. We find that (i) functional diversity generally declines with increasing latitude and elevation, (ii) temperature variability and vapor pressure are the strongest drivers of geographic shifts in functional composition and ecological strategies, and (iii) functional composition may currently be shifting over time due to rapid climate warming. Our analysis demonstrates that climate strongly governs functional diversity and provides essential information needed to predict how biodiversity and ecosystem function will respond to climate change.

Women's experiences and perceptions of anxiety and stress during the perinatal period: a systematic review and qualitative evidence synthesis.

BACKGROUND: The perinatal period, from pregnancy to the first year postpartum, is a transitional period that can result in anxiety and stress for some women. Perinatal anxiety and stress can adversely impact the physical and psychological health of women and children. Understanding women's lived experiences of perinatal anxiety and stress is essential to better support women. The aim of this qualitative evidence synthesis was to examine women's experiences and perceptions of, and barriers and facilitators to coping with, perinatal anxiety and stress. METHODS: Databases CINAHL, EMBASE, MEDLINE, PsycINFO and Maternity and Infant Care were searched from inception to June 2020. Eligible studies included women who were pregnant or up to one year postpartum and examined women's experiences of anxiety and/or stress during the perinatal period. Data were synthesised using thematic synthesis. RESULTS: Of 20,318 identified articles, 13 studies met inclusion criteria and were included in this review. Five key themes emerged: Social support, women's experiences of healthcare, social norms and expectations, factors that impact on coping and mother and baby's health. CONCLUSION: This review provided a comprehensive synthesis of perinatal anxiety and stress. Findings indicate that increased support for perinatal mental health in antenatal and postpartum care is needed. Addressing unrealistic expectations and conceptualisations of motherhood is also important to better support women. Enhancing women's social support networks and provision of clear and consistent information are also essential to support women and minimise stress and anxiety in the perinatal period.

Resolved Structural States of Calmodulin in Regulation of Skeletal Muscle Calcium Release.

Calmodulin (CaM) is proposed to modulate activity of the skeletal muscle sarcoplasmic reticulum (SR) calcium release channel (ryanodine receptor, RyR1 isoform) via a mechanism dependent on the conformation of RyR1-bound CaM. However, the correlation between CaM structure and functional regulation of RyR in physiologically relevant conditions is largely unknown. Here, we have used time-resolved fluorescence resonance energy transfer (TR-FRET) to study structural changes in CaM that may play a role in the regulation of RyR1. We covalently labeled each lobe of CaM (N and C) with fluorescent probes and used intramolecular TR-FRET to assess interlobe distances when CaM is bound to RyR1 in SR membranes, purified RyR1, or a peptide corresponding to the CaM-binding domain of RyR (RyRp). TR-FRET resolved an equilibrium between two distinct structural states (conformations) of CaM, each characterized by an interlobe distance and Gaussian distribution width (disorder). In isolated CaM, at low Ca2+, the two conformations of CaM are resolved, centered at 5 nm (closed) and 7 nm (open). At high Ca2+, the equilibrium shifts to favor the open conformation. In the presence of RyRp at high Ca2+, the closed conformation shifts to a more compact conformation and is the major component. When CaM is bound to full-length RyR1, either purified or in SR membranes, strikingly different results were obtained: 1) the two conformations are resolved and more ordered, 2) the open state is the major component, and 3) Ca2+ stabilized the closed conformation by a factor of two. We conclude that the Ca2+-dependent structural distribution of CaM bound to RyR1 is distinct from that of CaM bound to RyRp. We propose that the function of RyR1 is tuned to the Ca2+-dependent structural dynamics of bound CaM.

Predictors of Prescription Stimulant Misuse in U.S. College Graduates.

Background: Research has shown that prescription stimulant misuse (PSM) is prevalent among college students and that full-time college attendance is associated with PSM following graduation. Few studies, however, have examined predictors of PSM in college graduates. Objectives: We examined constructs from the Theory of Triadic Influence (TTI) to determine predictors of PSM in this population. Methods: We utilized Amazon's Mechanical Turk and snowball sampling in 2018-2019 to anonymously survey 219 adults in the United States (56% male, Mage = 32.5) with a college degree and history of college PSM. We assessed sensation seeking, ADHD symptoms, negative affect, social norms, workload, positive beliefs and perceived safety, other substance use, PSM motivations, and source(s) of prescription stimulants. Measures were administered online. Results: Over half (55%) of participants reported PSM after college; 36% used in the previous year. Ordinal logistic regressions for each domain of the TTI (i.e. intrapersonal, social/normative, cultural/attitudinal) showed that college graduates engaging in PSM in the previous year were younger and reported higher sensation seeking, more friends/coworkers who engaged in PSM, a heavier workload, and more positive beliefs about PSM. Chi-square analyses showed that college graduates engaging in PSM in the previous year also were more likely to use other substances (e.g. prescription opioids, tobacco/nicotine, cocaine) and to have misused stimulants in college to socialize or to get high. Conclusions: Preventive interventions could target college students and recent graduates who engage in PSM and who demonstrate the aforementioned risk factors, with the goal of curbing PSM and possibly other substance use.

Oxidation increases the strength of the methionine-aromatic interaction.

Oxidation of methionine disrupts the structure and function of a range of proteins, but little is understood about the chemistry that underlies these perturbations. Using quantum mechanical calculations, we found that oxidation increased the strength of the methionine-aromatic interaction motif, a driving force for protein folding and protein-protein interaction, by 0.5-1.4 kcal/mol. We found that non-hydrogen-bonded interactions between dimethyl sulfoxide (a methionine analog) and aromatic groups were enriched in both the Protein Data Bank and Cambridge Structural Database. Thermal denaturation and NMR spectroscopy experiments on model peptides demonstrated that oxidation of methionine stabilized the interaction by 0.5-0.6 kcal/mol. We confirmed the biological relevance of these findings through a combination of cell biology, electron paramagnetic resonance spectroscopy and molecular dynamics simulations on (i) calmodulin structure and dynamics, and (ii) lymphotoxin-α binding toTNFR1. Thus, the methionine-aromatic motif was a determinant of protein structural and functional sensitivity to oxidative stress.

Amdoparvovirus Infection in Red Pandas ( Ailurus fulgens).

Aleutian mink disease virus is the type species in the genus Amdoparvovirus, and in mink and other Mustelidae can cause either subclinical disease or fatal chronic immune stimulation and immune complex disease. The authors describe a novel amdoparvovirus in the endangered red panda ( Ailurus fulgens), discovered using viral metagenomics. The authors analyzed the prevalence, tissue distribution, and disease association by PCR, in situ hybridization, electron microscopy, and histology in a group of 6 red pandas from a single zoological collection. The study incorporates a fecal shedding survey and analysis of tissues from 4 necropsied animals over a 12-year span. The tentatively named red panda amdoparvovirus (RpAPV) was detected in the feces and/or tissues of all animals tested. At necropsy of 1 geriatric animal, infection was associated with pyogranulomatous peritonitis, pancreatitis, and myocarditis. Other animals had detectable low-level viral nucleic acid in lymph nodes and both oral and intestinal epithelium at the time of necropsy. Full-length genome sequences of RpAPV strains from 2 animals had 12% sequence divergence, demonstrating genetic diversity even among in-contact animals. RpAPV is a persistent infection in this cohort of red pandas, and has variable clinical expression.

Limiting the Exposure of Select Fetuses to Intrauterine Infection/Inflammation Improves Short-Term Neonatal Outcomes in Preterm Premature Rupture of Membranes.

BACKGROUND: To improve neonatal outcomes in pregnancies at heightened risk for early-onset neonatal sepsis (EONS), there is a need to identify fetuses that benefit from expectant management as opposed to early delivery. Detectable haptoglobin and haptoglobin-related protein (Hp&HpRP switch-on status) in cord blood has been proposed as a biomarker of antenatal exposure to intra-amniotic infection and/or inflammation (IAI), an important determinant of EONS. SUBJECTS AND METHODS: We analyzed 185 singleton newborns delivered secondary to preterm premature rupture of membranes (PPROM). In 123 cases, amniocentesis was performed to exclude amniotic fluid (AF) infection. Delivery was indicated for 61 cases with confirmed infection. Women without AF infection (n = 62) and those without amniocentesis (n = 62) were managed expectantly. Interleukin 6 and Hp&HpRP switch-on status were evaluated by ELISA and Western blot. Newborns were followed prospectively for short-term outcomes until hospital discharge or death. RESULTS: Newborns exposed antenatally to IAI had an increased risk of adverse neonatal outcome [OR: 3.0 (95% CI: 1.15-7.59)]. Increasing gestational age [OR: 0.61 (95% CI: 0.52-0.70)] and management with amniocentesis [OR: 0.37 (95% CI: 0.14-0.95)] lowered the newborn's risk of developing adverse outcomes. DISCUSSION: In the setting of PPROM and IAI, early delivery benefits a select subgroup of fetuses that have not yet progressed to Hp&HpRP switch-on status.

Impact of methionine oxidation on calmodulin structural dynamics.

We have used electron paramagnetic resonance (EPR) to examine the structural impact of oxidizing specific methionine (M) side chains in calmodulin (CaM). It has been shown that oxidation of either M109 or M124 in CaM diminishes CaM regulation of the muscle calcium release channel, the ryanodine receptor (RyR), and that mutation of M to Q (glutamine) in either case produces functional effects identical to those of oxidation. Here we have used site-directed spin labeling and double electron-electron resonance (DEER), a pulsed EPR technique that measures distances between spin labels, to characterize the structural changes resulting from these mutations. Spin labels were attached to a pair of introduced cysteine residues, one in the C-lobe (T117C) and one in the N-lobe (T34C) of CaM, and DEER was used to determine the distribution of interspin distances. Ca binding induced a large increase in the mean distance, in concert with previous X-ray crystallography and NMR data, showing a closed structure in the absence of Ca and an open structure in the presence of Ca. DEER revealed additional information about CaM's structural heterogeneity in solution: in both the presence and absence of Ca, CaM populates both structural states, one with probes separated by ∼4nm (closed) and another at ∼6nm (open). Ca shifts the structural equilibrium constant toward the open state by a factor of 13. DEER reveals the distribution of interprobe distances, showing that each of these states is itself partially disordered, with the width of each population ranging from 1 to 3nm. Both mutations (M109Q and M124Q) decrease the effect of Ca on the structure of CaM, primarily by decreasing the closed-to-open equilibrium constant in the presence of Ca. We propose that Met oxidation alters CaM's functional interaction with its target proteins by perturbing this Ca-dependent structural shift.

Respiratory Distress Caused by Neoplastic Upper Respiratory Tract Obstructions in 2 Pet Rats (Rattus norvegicus domestica).

Respiratory disease is one of the primary reasons for pet owners to seek veterinary attention for their rats. While chronic respiratory disease complex is most often responsible for respiratory signs in pet rats and is well characterized, upper respiratory obstructive disease has been rarely reported in the literature. This report describes 2 pet fancy rats (Rattus norvegicus domestica) presenting with a several day history of progressive respiratory signs that were minimally responsive to supportive therapies, including antibiotics, nonsteroidal anti-inflammatories, and fluid and oxygen support. Survey radiographs were performed under sedation in both cases. In the first case, no cause for the clinical signs could be identified, in part due to suboptimal radiographic positioning, although severe aerophagia was noted. In the second case, cervical tracheal luminal narrowing and increased soft tissue opacity along the walls of the trachea were identified. Both rats declined while under sedation, resulting in cardiopulmonary arrest in the first case and humane euthanasia in the second. On necropsy, the first case had a oropharyngeal squamous cell carcinoma originating from the Zymbal's gland, which was obstructing the larynx. The second case had an intra-luminal tracheal mass obstructing the airway. This was mostly likely B-cell lymphoma or a plasma cell tumor, although definitive diagnosis was unable to be obtained. For future such cases empiric management of respiratory disease in rats with antimicrobials, anti-inflammatories, and supportive care is often appropriate based on the high prevalence of infectious agents, however, other noninfectious causes should be considered, such as neoplastic processes leading to upper airway obstructive disease and diagnostic imaging may be indicated.

Petitions for Extreme Risk Protection Orders and Second Amendment Sanctuary Status in Colorado.

Importance: Extreme risk protection orders (ERPOs) temporarily bar individuals adjudicated as being at risk of violence (including suicide) from buying or possessing firearms. In protest, many US jurisdictions have declared themselves "Second Amendment sanctuaries" (2A sanctuaries). Many 2A sanctuaries continue to use ERPOs in low numbers, suggesting a poorly defined risk threshold at which they are acceptable. Objective: To characterize circumstances under which ERPOs are used in 2A sanctuaries, highlighting their most broadly acceptable applications. Design, Setting, and Participants: This cross-sectional study of civil court documents analyzed petitions for ERPOs filed in Colorado from January 2020 to December 2022. All petitions during the study period were included following de-duplication. These include petitions filed by law enforcement and family members against adults allegedly at risk of firearm violence across the state. Data were analyzed on a rolling basis between January 2020 and June 2023. Exposure: ERPO petition filed in Colorado. Main Outcomes and Measures: Seventy-seven data elements defined a priori were abstracted from all petitions and case files, including respondent demographics, petitioner types (family or law enforcement), types of threats (self, other, mass violence, combination), violence risk factors, and case outcomes (granted, denied). Results: Of a total 338 ERPOs filed in Colorado, 126 (37.3%) occurred in 2A sanctuaries. Sixty-one of these 2A petitions were granted emergency orders, and 40 were full 1-year ERPOs after a hearing. Forty ERPOs (31.7%) were petitioned for by law enforcement. Petitions in non-2A counties were more likely to have been filed by law enforcement (138 of 227 [64.9%] vs 40 of 126 [31.7%]; P < .001) and to have had an emergency order granted (177 of 227 [78.0%] vs 61 of 126 [48.4%]; P < .001) than in 2A sanctuaries. Qualitative analysis of cases in 2A sanctuaries revealed common aggravating risk characteristics, including respondents experiencing hallucinations, histories of police interaction, and substance misuse. ERPOs have been granted in 2A sanctuaries against individuals threatening all forms of violence we abstracted for (themselves, others, and mass violence). Conclusions and Relevance: In this examination of ERPO petitions across Colorado, more than a third of filings occurred in 2A sanctuaries. Nonetheless, law enforcement represent proportionately fewer petitions in these areas, and petitions are less likely to be granted. Serious mental illness, substance misuse, and prior interactions with law enforcement featured prominently in 2A sanctuary petitions. These case circumstances highlight dangerous situations in which ERPOs are an acceptable risk-prevention tool, even in areas politically predisposed to opposing them.

Quality assurance standards and their use in the preparation of parenteral systemic anticancer therapy products in healthcare establishments: a scoping review.

OBJECTIVES: The use of parenteral systemic anticancer therapy (SACT) has led to improved cancer survival. A quality assurance (QA) system of the aseptic compounding process is necessary to ensure safe and consistent production of parenteral SACT. This scoping review identifies international evidence and practice relating to QA standards in the preparation of parenteral SACT in healthcare establishments. METHODS: Standards relating to aseptic compounding in hospital pharmacies and literature exploring the aseptic compounding of parenteral SACT were included. Literature relating to the non-aseptic compounding of medicines and records specific to sterile manufacturing in industrial settings were excluded. A search of several electronic databases, trial registries, the grey literature and websites of key European hospital pharmacy groups and accreditation bodies was conducted on 16 March 2022. A narrative discussion was performed by country, and content analysis of articles was conducted. RESULTS: Thirty-seven records were included. Standards reviewed covered the work environment, the preparation process and the safety of the workers who are potentially exposed to hazardous chemicals. It was a common practice to include frequent audits to ensure adherence to standards. Some standards also recommended external inspections to allow for further learnings. Periodic reviews are encouraged to ensure standards maintain relevance. National standards of the countries reviewed were based on international standards, with minor adaptations for local conditions. CONCLUSIONS: The main limitation of this review is that it is limited to countries with a high human development index. The review shows that the use of an internationally recognised standard as a basis for national standards is best practice, and will allow for relevance into the future.