Structural insight into selectivity of amylin and calcitonin receptor agonists.

Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMY3R, and San45 bound to AMY3R or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMY3R. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects.

Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant.

The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.

Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit All?

In a multihospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model.

Understanding the host pathways that define susceptibility to Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in the Syrian hamster model. Pharmacological activation of HIF with the prolyl-hydroxylase inhibitor FG-4592 significantly reduced infectious virus in the upper and lower respiratory tract. Nasal and lung epithelia showed a reduction in SARS-CoV-2 RNA and nucleocapsid expression in treated animals. Transcriptomic and pathological analysis showed reduced epithelial damage and increased expression of ciliated cells. Our study provides new insights on the intrinsic antiviral properties of the HIF signalling pathway in SARS-CoV-2 replication that may be applicable to other respiratory pathogens and identifies new therapeutic opportunities.

Treating new-onset cognitive complaints after risk-reducing salpingo-oophorectomy: A randomized controlled crossover trial of lisdexamfetamine.

OBJECTIVE: To determine whether the psychostimulant lisdexamfetamine improves subjective and objective measures of cognitive functioning among women genetically at-risk for cancer who have undergone risk-reducing salpingo-oophorectomy and report new-onset executive functioning difficulties. METHODS: 69 participants were assigned to a randomized controlled crossover trial with 6-week trials of active medication (lisdexamfetamine) and placebo, separated by a minimum 2-week washout in an intent-to-treat framework (clinical trial registration number: NCT03187353). At trial baseline, midpoint, and endpoint, participants completed a self-report measure of executive functioning (Brown Attention Deficit Disorder Scale). At study baseline and trial endpoint, participants completed sustained attention, attention/working memory, and verbal learning/memory cognitive tasks. Side effects were assessed at 2, 3, 4, and 6 weeks for each trial. RESULTS: From trial baseline to trial endpoint, lisdexamfetamine - relative to placebo - significantly improved total scores on the self-report Brown Attention Deficit Disorder Scale (and scores on four of five subdomains) as well as attention and working memory performance. Significantly more participants endorsed side effects across the lisdexamfetamine trial versus placebo; however, trial completion rates were similar, indicating that lisdexamfetamine was nonetheless well-tolerated. CONCLUSIONS: Lisdexamfetamine improved both subjective and objective measures of attention and working memory and could offer women experiencing cognitive difficulties post-risk-reducing salpingo-oophorectomy an alternative therapeutic option.

Membranes under the Magnetic Lens: A Dive into the Diverse World of Membrane Protein Structures Using Cryo-EM.

Membrane proteins are highly diverse in both structure and function and can, therefore, present different challenges for structure determination. They are biologically important for cells and organisms as gatekeepers for information and molecule transfer across membranes, but each class of membrane proteins can present unique obstacles to structure determination. Historically, many membrane protein structures have been investigated using highly engineered constructs or using larger fusion proteins to improve solubility and/or increase particle size. Other strategies included the deconstruction of the full-length protein to target smaller soluble domains. These manipulations were often required for crystal formation to support X-ray crystallography or to circumvent lower resolution due to high noise and dynamic motions of protein subdomains. However, recent revolutions in membrane protein biochemistry and cryo-electron microscopy now provide an opportunity to solve high resolution structures of both large, >1 megadalton (MDa), and small, <100 kDa (kDa), drug targets in near-native conditions, routinely reaching resolutions around or below 3 Å. This review provides insights into how the recent advances in membrane biology and biochemistry, as well as technical advances in cryo-electron microscopy, help us to solve structures of a large variety of membrane protein groups, from small receptors to large transporters and more complex machineries.

Impact of Asian and Black Donor and Recipient Ethnicity on the Outcomes After Deceased Donor Kidney Transplantation in the United Kingdom.

Patients of Asian and black ethnicity face disadvantage on the renal transplant waiting list in the UK, because of lack of human leucocyte antigen and blood group matched donors from an overwhelmingly white deceased donor pool. This study evaluates outcomes of renal allografts from Asian and black donors. The UK Transplant Registry was analysed for adult deceased donor kidney only transplants performed between 2001 and 2015. Asian and black ethnicity patients constituted 12.4% and 6.7% of all deceased donor recipients but only 1.6% and 1.2% of all deceased donors, respectively. Unadjusted survival analysis demonstrated significantly inferior long-term allograft outcomes associated with Asian and black donors, compared to white donors. On Cox-regression analysis, Asian donor and black recipient ethnicities were associated with poorer outcomes than white counterparts, and on ethnicity matching, compared with the white donor-white recipient baseline group and adjusting for other donor and recipient factors, 5-year graft outcomes were significantly poorer for black donor-black recipient, Asian donor-white recipient, and white donor-black recipient combinations in decreasing order of worse unadjusted 5-year graft survival. Increased deceased donation among ethnic minorities could benefit the recipient pool by increasing available organs. However, it may require a refined approach to enhance outcomes.

Addressing emerging issues in entomology: 2023 student debates.

The Entomological Society of America (ESA) Student Debates is an annual student competition at the ESA Annual Meeting organized by Student Debates Subcommittee (SDS) members of the ESA Student Affairs Committee. In conjunction with the 2023 ESA Annual Meeting theme, 'Insects and influence: Advancing entomology's impact on people and policy', the theme of this year's student debate was 'Addressing emerging issues in entomology'. With the aid of ESA membership, the SDS selected the following debate topics: (1) Should disclosure of artificial intelligence large language models in scientific writing always be required? and (2) Is it more important to prioritize honey bee or native pollinator health for long-term food security within North America? Four student teams from across the nation, composed of 3-5 student members and a professional advisor, were assigned a topic and stance. Over the course of 5 months, all team members researched and prepared for their assigned topic before debating live with an opposing team at the 2023 ESA Annual Meeting in National Harbor, Maryland. SDS members additionally prepared and presented introductions for each debate topic to provide unbiased backgrounds to the judges and audience for context in assessing teams' arguments. The result was an engaging discussion between our teams, judges, and audience members on emerging issues facing entomology and its impact on people and policy, such as scientific communication and food security, that brought attention to the complexities involved when debating topics concerning insects and influence.

The Use of Remote Presence Robotic Tele-Presentation in Rural and Remote Canada: A Systematic Review.

Objective: One potential solution to limited health care in rural and remote regions is remote presence robotic tele-presentation to allow health care providers to care for patients in their home community via a robotic interface. We synthesized evidence regarding the use of remote presence robotic tele-presentation in rural and/or remote Canadian health settings. Methods: Medline, PubMed, and Embase were searched up to August 2023. Remote presence robotic tele-presentation refers to any robotic device used for the purpose of presenting and/or collecting patient information. Primary research was included if the patient was located in remote and/or rural Canada, featured remote presence robotic tele-presentation, and assessed patient, family, or clinician satisfaction, patient transport to nearby regional or urban center, health care costs, clinical outcomes, infrastructure outcomes, adverse events, or telementoring. Results: Six studies were included. Patients, nurses, and physicians all reported high levels of satisfaction when using the remote presence robotic tele-presentation. Fifty to sixty-three percent of patients were managed in their home community and did not require transfer to another center. Remote presence robotic sonography resulted in adequate imaging in 81% of first trimester ultrasound limited exams but was less useful for second trimester complete obstetric ultrasounds (20% adequate imaging). Two of eight laparoscopic colorectal surgeries had to be converted to open surgeries. Telerobotic ultrasound clinics resulted in a diagnosis in 70% of cases. Conclusions: Evidence suggests remote presence robotic tele-presentation is a safe and cost-effective approach to providing care in distant communities and can prevent some transfers and evacuations to tertiary hospitals.

Integrating otolith and genetic tools to reveal intraspecific biodiversity in a highly impacted salmon population.

Intraspecific biodiversity is vital for species persistence in an increasingly volatile world. By embracing methods that integrate information at different spatiotemporal scales, we can directly monitor and reconstruct changes in intraspecific biodiversity. Here we combined genetics and otolith biochronologies to describe the genotypic and phenotypic diversity of Chinook salmon (Oncorhynchus tshawytscha) in the Yuba River, California, comparing cohorts that experienced a range of hydroclimatic conditions. Yuba River salmon have been heavily impacted by habitat loss and degradation, and large influxes of unmarked hatchery fish each year have led to concern about introgression and uncertainty around the viability of its wild populations, particularly the rarer spring-run salmon. Otolith strontium isotopes showed that Yuba River origin fish represented, on average, 42% (range 7%-73%) of spawners across six return years (2009-2011, 2018-2020), with large interannual variability. The remainder of adult Chinook salmon in the river were primarily strays from the nearby Feather River hatchery, and since 2018 from the Mokelumne River hatchery. Among the Yuba-origin spawners, on average, 30% (range 14%-50%) exhibited the spring-run genotype. The Yuba-origin fish also displayed a variety of outmigration phenotypes that differed in the timing and size at which they left the Yuba river. Early-migrating fry dominated the returns (mean 59%, range 33%-89%), and their contribution rates were negatively correlated with freshwater flows. It is unlikely that fry survival rates are elevated during droughts, suggesting that this trend reflects disproportionately low survival of larger later migrating parr, smolts, and yearlings along the migratory corridor in drier years. Otolith daily increments indicated generally faster growth rates in non-natal habitats, emphasizing the importance of continuing upstream restoration efforts to improve in-river growing conditions. Together, these findings show that, despite a long history of habitat degradation and hatchery introgression, the Yuba River maintains intraspecific biodiversity that should be taken into account in future management, restoration, and reintroduction plans. The finding that genotypic spring-run are reproducing, surviving, and returning to the Yuba River every year suggests that re-establishment of an independent population is possible, although hatchery-wild interactions would need to be carefully considered. Integrating methods is critical to monitor changes in key genetic, physiological, and behavioral traits to assess population viability and resilience.

Quantifying head impact biomechanical differences between commonly employed cleaning levels: a critical research interpretation consideration.

INTRODUCTION: Wearable accelerometry devices quantify on-field frequency and severity of head impacts to further improve sport safety. Commonly employed post-data collection cleaning techniques may affect these outcomes. OBJECTIVE: Our purpose was to compare game impact rates and magnitudes between three different cleaning levels (Level-1: impacts recorded within start and end times, Level-2: impacts during pauses/breaks removed, Level-3: video verified) for male youth tackle football. METHODS: Participants (n = 23, age = 10.9 ± 0.3 yrs, height = 150.0 ± 8.3 cm, mass = 41.6 ± 8.4 kg) wore Triax SIM-G sensors throughout Fall 2019. Impact rates, ratios (IRRs), and 95% confidence intervals (95%CI) were used to compare levels. Random-effects general linear models were used to compare peak linear acceleration (PLA;g) and angular velocity (PAV;rads/s). RESULTS: Level-1 resulted in higher impact rates (4.57; 95%CI = 4.14-5.05) compared to Level-2 (3.09; 95%CI = 2.80-3.42; IRR = 1.48; 95%CI = 1.34-1.63) and Level-3 datasets (2.56; 95%CI = 2.30-2.85; IRR = 1.78; 95%CI = 1.60-1.98). Level-2 had higher impact rates compared to Level-3 (1.21; 95%CI = 1.08-1.35). Level-1 resulted in higher PAV than Level-2 and Level-3 (p < 0.001) datasets. PLA did not differ across datasets (p = 0.296). CONCLUSIONS: Head impact data should be filtered of pauses/breaks, and does not substantially differ outcome estimates compared to time-intensive video verification.

Use of Virtual Care Strategies to Join Multidisciplinary Teams Evaluating Work-Related Injuries in Rural Residents.

Background: Rural injured workers requiring multidisciplinary assessments for musculoskeletal disorders face health access disparities, which include travel to urban centers. Virtual care can enhance access to multidisciplinary team care for musculoskeletal conditions in rural areas. Materials and Methods: A retrospective chart audit of 136 multidisciplinary assessment reports of injured workers was conducted. Comprehensive management recommendations from the health care assessment team were extracted for analysis. The health care team used virtual technologies to join with patients and at least one local rural health practitioner in one of three locations. Remote presence robotics (RPR; Xpress Technology™) or laptop-based telehealth was used to complete the assessments. Results: RPR were used in 46% of assessments over two sites, with 54% using laptop-based telehealth at a third site. Frequencies of team members' assessment using technologies were as follows: physical therapist (100%), psychologist (78%), plastic surgeon (8%), and physician (43%). Spine (42%) and shoulder (32%) disorders were the most common problems. Most workers (79%) were 3 or more months postinjury. The most common management recommendation was the need for daily comprehensive rehabilitation care (76%). Travel time was saved by 89% of participants. Conclusions: Virtual care was used to unite multidisciplinary assessment teams for the evaluation of injured rural workers with complex musculoskeletal injuries. Future research recommendations include comparing between virtual and fully in-person multidisciplinary assessment and recommendation findings, and evaluation of patient and practitioner experiences with comprehensive virtual team assessments.

Jump Height and Hip Power Decrease During Cognitive Loading Regardless of Sex: Implications for Sport Performance Metrics.

ABSTRACT: Shumski, EJ, Lempke, LB, Johnson, RS, Oh, J, Schmidt, JD, and Lynall, RC. Jump height and hip power decrease during cognitive loading regardless of sex: implications for sport performance metrics. J Strength Cond Res 37(4): 793-798, 2023-Sex and cognitive loading separately influence jumping performance. However, it is unknown how cognitive loading influences jump performance and how sex and cognitive loading interact. The purpose of our study was to determine if an interaction existed between sex and cognitive loading for the dependent variables jump height, ground contact time, reactive strength index, vertical stiffness, impulse, and lower extremity joint power during a double limb drop vertical jump. Twenty-one male (23.2 ± 2.5 years, 180.8 ± 8.4 cm, 80.4 ± 10.2 kg) and 20 female (21.7 ± 1.0 years, 163.7 ± 8.2 cm, 61.2 ± 9.4 kg) physically active individuals participated. Subjects jumped from a 30 cm box placed 50% of their height away from 2 force plates under single-task and dual-task (serial 6s or 7s) conditions. Separate 2 × 2 analyses of variance were used for all dependent variables (α = 0.05) with Bonferroni post hoc mean differences and 95% confidence intervals (CIs). There were no significant interactions for any outcomes ( p ≥ 0.190). Condition main effects demonstrated subjects jumped significantly higher (1.84 cm, 95% CI = 0.68-3.01, d = 0.26, p = 0.003) and with greater hip power (0.29 Watts·BW -1 ·HT -1 , 95% CI = 0.04-0.54, d = 0.21, p = 0.025) during single task compared with dual task. Sex main effects revealed males jumped higher (9.88 cm, 95% CI = 7.00-12.77, d = 2.17, p < 0.001), with greater reactive strength index (0.29, 95% CI = 0.17-0.41, d = 1.52, p < 0.001), greater ankle power (3.70 Watts·BW -1 ·HT -1 , 95% CI = 2.26-5.13, d = 1.64, p < 0.001), and greater knee power (5.00 Watts·BW -1 ·HT -1 , 95% CI = 3.25-6.75, d = 1.82, p < 0.001) compared with females. Jump performance is influenced by sex and dual-task conditions but not their interaction. To optimize jumping performance, testing should be completed without distractions (single task) to decrease cognitive loading.

American Trauma Care: A System of Systems.

OBJECTIVE: The benefits of organized trauma systems have been well-documented during 50 years of trauma system development in the United States. Unfortunately, despite this evidence, trauma system development has occurred only sporadically in the 50 states. METHODS: The relevant literature related to trauma system design and development was reviewed based on relevance to the study. Information from these sources was summarized into a SWOT (strengths, weaknesses, opportunities, and threats) analysis. RESULTS: Strengths discovered were leadership brought forth by the American College of Surgeons Committee on Trauma and meaningful change generated from The National Academy of Sciences, Engineering, and Medicine report addressing the fractionation of the nation's trauma systems, whereas weaknesses included patient outcome disparities due to the lack of a national governing authority, undertriage, underresourced rural trauma, and underfunded trauma research. Opportunities included the creation of level IV trauma centers; telemedicine; the development of rural trauma management courses; air medical transport to bring high-intensity care to the patient, particularly in rural areas; trauma research; and trauma prevention through outreach and educational programs. The following threats were determined: mass casualty incidents, motor vehicle collisions because of the high rate of motor vehicle collision deaths in the United States relative to other developed countries, and underfunded trauma systems. CONCLUSION: Much work remains to be done in the development of an American trauma system. Recommendations include implementation of trauma care governance at the federal level; national oversight and support of emergency medical services systems, particularly in rural areas with strict reporting processes for emergency medical services programs; national organization of our mass casualty response; increased federal and state funding allocated to trauma centers; a consistent model for trauma system development; and trauma research.

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.

Antibody and T-cell responses by ultra-deep T-cell receptor immunosequencing after COVID-19 vaccination in patients with plasma cell dyscrasias.

We investigated antibody and coronavirus disease 2019 (COVID-19)-specific T-cell mediated responses via ultra-deep immunosequencing of the T-cell receptor (TCR) repertoire in patients with plasma cell dyscrasias (PCD). We identified 364 patients with PCD who underwent spike antibody testing using commercially available spike-receptor binding domain immunoglobulin G antibodies ≥2 weeks after completion of the initial two doses of mRNA vaccines or one dose of JNJ-78436735. A total of 56 patients underwent TCR immunosequencing after vaccination. Overall, 86% tested within 6 months of vaccination had detectable spike antibodies. Increasing age, use of anti-CD38 or anti-B-cell maturation antigen therapy, and receipt of BNT162b2 (vs. mRNA-1273) were associated with lower antibody titres. We observed an increased proportion of TCRs associated with surface glycoprotein regions of the COVID-19 genome after vaccination, consistent with spike-specific T-cell responses. The median spike-specific T-cell breadth was 3.11 × 10-5 , comparable to those in healthy populations after vaccination. Although spike-specific T-cell breadth correlated with antibody titres, patients without antibody responses also demonstrated spike-specific T-cell responses. Patients receiving mRNA-1273 had higher median spike-specific T-cell breadth than those receiving BNT162b2 (p = 0.01). Although patients with PCD are often immunocompromised due to underlying disease and treatments, COVID-19 vaccination can still elicit humoral and T-cell responses and remain an important intervention in this patient population.

Utilization and clinical outcomes of kidney transplants from deceased donors with albuminuria in the UK: a national cohort study.

BACKGROUND: Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilization, survival and function. METHODS: We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥2+ on dipstick testing, on kidney utilization, early graft function, graft failure and estimated glomerular filtration rate (eGFR). RESULTS: Eighteen percent (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% versus 82%; odds ratio 0.70, 95% confidence interval 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (hazard ratio 0.91, 95% confidence interval 0.74 to 1.11). There was also no association with delayed graft function, patient survival or eGFR at 1 or 3 years. CONCLUSIONS: Our study suggests reluctance in the UK to utilize kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilization without negatively impacting transplant outcomes.

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.

Central venous catheter-associated deep vein thrombosis in critically ill pediatric patients: risk factors, prevention, and treatment.

PURPOSE OF REVIEW: Central venous catheter (CVC) placement and ICU admission are the two most important risk factors for pediatric deep vein thrombosis. The optimal prevention and treatment strategies for CVC-associated deep vein thrombosis (CADVT) are unclear, but recently, seminal studies have been published. This review aims to summarize the recent literature on CADVT in critically ill children. RECENT FINDINGS: Recent publications focused on three themes: risk factors, prevention, and treatment of CADVT. Newly identified risk factors for CADVT relate to Virchow's triad of hemostasis, blood vessel injury, and hypercoagulability. New risk prediction models have moderately good accuracy in predicting CADVT. Though previous data on pharmacologic CADVT prophylaxis was equivocal, recent studies indicate that low-molecular-weight heparin may be effective in preventing CADVT, particularly in critically ill children. Finally, new studies suggest that direct oral anticoagulants and shorter treatment times are noninferior to traditional agents and treatment durations in the treatment of CADVT. SUMMARY: Recent research suggests new ways to accurately identify children at high risk of CADVT, effectively prevent CADVT, and optimize CADVT treatment. Future research should focus on understanding the pathobiology of CADVT formation, prevention, and treatment in critically ill children.