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Acute and chronic upper respiratory illnesses such as asthma, and allergic rhinitis (AR) have been linked to the presence of microorganisms in the nose. Microorganisms can exist in symbiotic or commensal relationships with the human body. However, in certain cases, opportunistic pathogens can take over, leading to altered states (dysbiosis) and causing disease. Thus, the microflora present in a host can be useful to reflect health status. The human body contains 10 trillion to 100 trillion microorganisms. Of these populations, certain pathogens have been identified to promote or undermine wellbeing. Therefore, knowledge of the microbiome is potentially helpful as a diagnostic tool for many diseases. Variations have been recognized in the types of microbes that inhabit various populations based on geography, diet, and lifestyle choices and various microbiota have been shown to modulate immune responses in allergic disease. Interestingly, the diseases affected by these changes are prevalent in certain racial or ethnic populations. These prevalent microbiome variations in these groups suggest that the presence of these microorganisms may be significantly associated with health disparities. We review current research in the search for correlations between ethnic diversity, microbiome communities in the nasal cavity and health outcomes in neurological and respiratory functions.

The cochlear implant, a bionic technology that restores sound sensation in some patients, has become ethically controversial in the 20 years since its introduction. This controversy recently has entered American entertainment culture, with the issue of pediatric implants emerging in episodes of popular TV programs. This pilot study examines the effects of one such TV episode on the attitudes of hearing college students with minimal prior exposure to the controversy, using a posttest-only control group design. The control group (N = 17) watched an unrelated entertainment video and filled out an original 10-item attitude scale. The treatment group (N = 18), which viewed an episode of the dramatic series Gideon's Crossing addressing the cochlear implant issue, also filled out the attitude scale. A t test was applied, and it was determined that no significant difference existed between the two groups' attitudes regarding pediatric cochlear implants. Although there was wide variability on individual items, overall scores indicated that both groups were neutral, or undecided, regarding cochlear implantation in children. [ABSTRACT FROM AUTHOR]

The article presents an obituary for medical personnel Dorothea Miller.

Abstract Introduction Spinal cord compression is a potentially devastating condition that demands immediate attention. Efforts must be divided between addressing the symptoms of cord compression and identifying the precise etiology of the condition. Case presentation A 76-year-old Peruvian man presented to our emergency department for evaluation of the gradual onset of lower extremity weakness over one month, resulting in falls and a two day history of bladder and bowel incontinence. Surprisingly, the etiology of this case of spinal cord compression was found to be multiple myeloma presenting as a solid tumor. Conclusion We report a case of a spinal cord mass resulting in symptoms of cord compression that was diagnosed when aspects of our patient's initial magnetic resonance imaging scan did not correlate with disc herniation, which was the diagnosis with the greatest pretest probability.

Abstract Background We have previously identified associations between major histocompatibility complex (MHC) class I and resistance towards bacterial and viral pathogens in Atlantic salmon. To evaluate if only MHC or also closely linked genes contributed to the observed resistance we ventured into sequencing of the duplicated MHC class I regions of Atlantic salmon. Results Nine BACs covering more than 500 kb of the two duplicated MHC class I regions of Atlantic salmon were sequenced and the gene organizations characterized. Both regions contained the proteasome components PSMB8, PSMB9, PSMB9-like and PSMB10 in addition to the transporter for antigen processing TAP2, as well as genes for KIFC1, ZBTB22, DAXX, TAPBP, BRD2, COL11A2, RXRB and SLC39A7. The IA region contained the recently reported MHC class I Sasa-ULA locus residing approximately 50 kb upstream of the major Sasa-UBA locus. The duplicated class IB region contained an MHC class I locus resembling the rainbow trout UCA locus, but although transcribed it was a pseudogene. No other MHC class I-like genes were detected in the two duplicated regions. Two allelic BACs spanning the UBA locus had 99.2% identity over 125 kb, while the IA region showed 82.5% identity over 136 kb to the IB region. The Atlantic salmon IB region had an insert of 220 kb in comparison to the IA region containing three chitin synthase genes. Conclusion We have characterized the gene organization of more than 500 kb of the two duplicated MHC class I regions in Atlantic salmon. Although Atlantic salmon and rainbow trout are closely related, the gene organization of their IB region has undergone extensive gene rearrangements. The Atlantic salmon has only one class I UCA pseudogene in the IB region while trout contains the four MHC UCA, UDA, UEA and UFA class I loci. The large differences in gene content and most likely function of the salmon and trout class IB region clearly argues that sequencing of salmon will not necessarily provide information relevant for trout and vice versa.

Background: Despite the increase in firearm injury observed across the country, significant gaps remain relevant to our understanding of how firearm exposure translates to injury. Using acoustic gunshot detection and a collaborative hospital and law enforcement firearm injury database, we sought to identify the relationship between firearm discharge and injury over time., Study Design: From 2018 to 2021, instances of firearm discharge captured via acoustic detection in 6 square miles of Louisville, KY, were merged with data from the collaborative firearm injury database. Key outcomes included the total number of rounds fired, injury and fatality rates per round, and the percentage of rounds discharged from automatic weapons and high-capacity magazines., Results: During the study period, 54,397 rounds of ammunition were discharged resulting in 914 injuries, 435 hospital admissions, 2,442 hospital days, 155 emergent operations, and 180 fatalities. For each round of ammunition fired, the risk of injury and fatality was 1.7% and 0.3%, respectively. The total number of rounds fired per month nearly tripled (614 vs 1,623, p < 0.001) leading to increased injury (15 vs 37, p < 0.001) and fatality (3 vs 7, p < 0.001). The percentage of rounds fired from automatic weapons (0 vs 6.8%, p < 0.001) and high-capacity magazines (7.6 vs 28.9%, p < 0.001) increased over time., Conclusions: The increased burden of firearm injury is related to an overall increase in firearm exposure as measured by the total number of rounds discharged. High-capacity magazines and automatic weaponry are being used with increasing frequency in urban America., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Many children with severe traumatic brain injury (TBI) receive magnetic resonance imaging (MRI) during hospitalization. There are insufficient data on how different patterns of injury on early MRI inform outcomes., Methods: Children (3-17 years) admitted in 2010-2021 for severe TBI (Glasgow Coma Scale [GCS] score < 9) were identified using our site's trauma registry. We used multivariable modeling to determine whether the hemorrhagic diffuse axonal injury (DAI) grade and the number of regions with restricted diffusion (subcortical white matter, corpus callosum, deep gray matter, and brainstem) on MRI obtained within 7 days of injury were independently associated with time to follow commands and with Functional Independence Measure for Children (WeeFIM) scores at the time of discharge from inpatient rehabilitation. We controlled for the clinical variables age, preadmission cardiopulmonary resuscitation, pupil reactivity, motor GCS score, and fever (> 38 °C) in the first 12 h., Results: Of 260 patients, 136 (52%) underwent MRI within 7 days of injury at a median of 3 days (interquartile range [IQR] 2-4). Patients with early MRI were a median age of 11 years (IQR 7-14), 8 (6%) patients received cardiopulmonary resuscitation, 19 (14%) patients had bilateral unreactive pupils, the median motor GCS score was 1 (IQR 1-4), and 82 (60%) patients had fever. Grade 3 DAI was present in 46 (34%) patients, and restricted diffusion was noted in the corpus callosum in 75 (55%) patients, deep gray matter in 29 (21%) patients, subcortical white matter in 23 (17%) patients, and the brainstem in 20 (15%) patients. After controlling for clinical variables, an increased number of regions with restricted diffusion, but not hemorrhagic DAI grade, was independently associated with longer time to follow commands (hazard ratio 0.68, 95% confidence interval 0.53-0.89) and worse WeeFIM scores (estimate β - 4.67, 95% confidence interval - 8.33 to - 1.01)., Conclusions: Regional restricted diffusion on early MRI is independently associated with short-term outcomes in children with severe TBI. Multicenter cohort studies are needed to validate these findings and elucidate the association of early MRI features with long-term outcomes in children with severe TBI., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products., Methods: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days - 7, - 2, 21, and 28, and tick counts were performed on day - 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons., Results: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24-48 h earlier for lotilaner compared with sarolaner or afoxolaner., Conclusions: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period., (© 2024. The Author(s).)

Objective: To characterize seizure tracking patterns of people with focal epilepsy using electronic seizure diary entries, and to assess for risk factors associated with poor tracking., Methods: We analyzed electronic seizure diary data from 410 participants with newly diagnosed focal epilepsy in the Human Epilepsy Project 1 (HEP1). Each participant was expected to record data each day during the study, regardless of seizure occurrence. The primary outcome of this post-hoc analysis was whether each participant properly tracked a seizure diary entry each day during their study participation. Using finite mixture modeling, we grouped patient tracking trajectories into data-driven clusters. Once defined, we used multinomial modeling to test for independent risk factors of tracking group membership., Results: Using over up to three years of daily seizure diary data per subject, we found four distinct seizure tracking groups: consistent, frequent at study onset, occasional, and rare. Participants in the consistent tracking group tracked a median of 92% (interquartile range, IQR: 82%, 99%) of expected days, compared to 47% (IQR:34%, 60%) in the frequent at study onset group, 37% (IQR: 26%, 49%) in the occasional group, and 9% (IQR: 3%, 15%) in the rare group. In multivariable analysis, consistent trackers had lower rates of seizure days per tracked year during their study participation, compared to other groups., Significance: Future efforts need to focus on improving seizure diary tracking adherence to improve quality of outcome data, particularly in those with higher seizure burden. In addition, accounting for missing data when using seizure diary data as a primary outcome is important in research trials. If not properly accounted for, total seizure burden may be underestimated and biased, skewing results of clinical trials., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: To describe the process of breastfeeding relationships among stay-at-home mother and infant dyads at 1, 3, 5 and 6 months., Design: A longitudinal qualitative online survey design was used., Methods: Data were obtained at 1, 3, 5 and 6 months from 26 breastfeeding mothers who stayed home with their infants and directly breastfed at least once a day for the first 6 months between June 2022 and August 2023. Mothers' written responses to 3 open-ended questions were analysed to assess breastfeeding experiences at home, thoughts/comments while directly breastfeeding and breastfeeding concerns/problems and strategies they used. Based on grounded theory, inductive content analysis was used to analyse the data. Trustworthiness of results was established by coding to consensus, formal peer debriefing and maintaining an audit trail., Results: 'Breastfeeding Relationships at Home,' the core construct, was identified and organized the process of breastfeeding relationships into 5 domains: (1) mothers' emotional well-being while breastfeeding, (2) infant-led feeding, (3) alternatives to breastfeeding, (4) evaluation of breastfeeding and (5) changes in breastfeeding as infants grow older., Conclusion: Breastfeeding is not simply about feeding breast milk but also involves nurturing and developing a relationship between mother and infant. Across the domains, mutual responsiveness, a central element of the breastfeeding relationship was clear. Mothers who were committed to breastfeeding with embedded infant suckling reached emotional well-being in return for their engagement which has potential to reduce maternal stress and prevent postpartum depression., Impact: Findings from the current study add to nurses' knowledge about the relationship building process between stay-at-home mothers and their infants in the first 6 months of breastfeeding during the COVID-19 pandemic. Nurses must remain sensitive to aid the development of breastfeeding relationships in the home environment to maximize mutual responsiveness., Patient or Public Contribution: No patients or public involved., (© 2024 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Objectives: To characterize health-related quality of life (HRQL) and functional recovery trajectories and risk factors for prolonged impairments among critically ill children receiving greater than or equal to 3 days of invasive ventilation., Design: Prospective cohort study., Setting: Quaternary children's hospital PICU., Patients: Children without a preexisting tracheostomy who received greater than or equal to 3 days of invasive ventilation, survived hospitalization, and completed greater than or equal to 1 postdischarge data collection., Interventions: None., Measurements and Main Results: We evaluated 144 children measuring HRQL using proxy-report Pediatric Quality of Life Inventory and functional status using the Functional Status Scale (FSS) reflecting preillness baseline, PICU and hospital discharge, and 1, 3, 6, and 12 months after hospital discharge. They had a median age of 5.3 years (interquartile range, 1.1-13.0 yr), 58 (40%) were female, 45 (31%) had a complex chronic condition, and 110 (76%) had normal preillness FSS scores. Respiratory failure etiologies included lung disease ( n = 49; 34%), neurologic failure ( n = 23; 16%), and septic shock ( n = 22; 15%). At 1-month postdischarge, 68 of 122 (56%) reported worsened HRQL and 35 (29%) had a new functional impairment compared with preillness baseline. This improved at 3 months to 54 (46%) and 24 (20%), respectively, and remained stable through the remaining 9 months of follow-up. We used interaction forests to evaluate relative variable importance including pairwise interactions and found that therapy consultation within 3 days of intubation was associated with better HRQL recovery in older patients and those with better preillness physical HRQL. During the postdischarge year, 76 patients (53%) had an emergency department visit or hospitalization, and 62 (43%) newly received physical, occupational, or speech therapy., Conclusions: Impairments in HRQL and functional status as well as health resource use were common among children with acute respiratory failure. Early therapy consultation was a modifiable characteristic associated with shorter duration of worsened HRQL in older patients., Competing Interests: Dr. Maddux’s institution received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (K23HD096018) and the Francis Family Foundation, Parker B. Francis Award. Drs. Maddux and Mourani received support for article research from the National Institutes of Health (NIH). Dr. Bennett’s institution received funding from the NICHD, the National Heart, Lung, and Blood Institute, and the National Center for Advancing Translational Sciences. Dr. Spear disclosed that a trust with him as beneficiary owns mutual funds that may own stock in pharmaceuticals. Dr. Mourani’s institution received funding from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Penetrating cardiac injuries usually require emergent surgical intervention. Our patient presented to the trauma centre with multiple stab wounds to the neck, chest, epigastric region and abdomen. She arrived haemodynamically stable, and her initial Focused Assessment with Sonography for Trauma exam was negative. Her chest X-ray did not show any evident pneumothorax or haemothorax. Due to her injury pattern, she was taken to the operating room for exploratory laparotomy and neck exploration. Postoperatively, she was taken for CT and found to have a contained cardiac rupture. The injury was contained within previous scar tissue from her prior cardiac surgery. Further evaluation revealed that the injury included a penetrating stab wound to the right ventricle and a traumatic ventricular septal defect (VSD). She subsequently underwent a redo sternotomy with the repair of the penetrating stab wound and the VSD. Cardiology, intensive care, trauma surgery and cardiothoracic surgery coordinated her care from diagnosis, management and recovery. This case highlights the challenges in the management of cardiac injuries and the benefits of a multidisciplinary approach to care for complex cardiac injuries., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sepsis-associated destruction of the pulmonary microvascular endothelial glycocalyx (EGCX) creates a vulnerable endothelial surface, contributing to the development of acute respiratory distress syndrome (ARDS). Constituents of the EGCX shed into circulation, glycosaminoglycans and proteoglycans, may serve as biomarkers of endothelial dysfunction. We sought to define the patterns of plasma EGCX degradation products in children with sepsis-associated pediatric ARDS (PARDS), and test their association with clinical outcomes., Methods: We retrospectively analyzed a prospective cohort (2018-2020) of children (≥1 month to <18 years of age) receiving invasive mechanical ventilation for acute respiratory failure for ≥72 h. Children with and without sepsis-associated PARDS were selected from the parent cohort and compared. Blood was collected at time of enrollment. Plasma glycosaminoglycan disaccharide class (heparan sulfate, chondroitin sulfate, and hyaluronan) and sulfation subtypes (heparan sulfate and chondroitin sulfate) were quantified using liquid chromatography tandem mass spectrometry. Plasma proteoglycans (syndecan-1) were measured through an immunoassay., Results: Among the 39 mechanically ventilated children (29 with and 10 without sepsis-associated PARDS), sepsis-associated PARDS patients demonstrated higher levels of heparan sulfate (median 639 ng/mL [interquartile range, IQR 421-902] vs 311 [IQR 228-461]) and syndecan-1 (median 146 ng/mL [IQR 32-315] vs 8 [IQR 8-50]), both p  = 0.01. Heparan sulfate subtype analysis demonstrated greater proportions of N -sulfated disaccharide levels among children with sepsis-associated PARDS ( p =  0.01). Increasing N- sulfated disaccharide levels by quartile were associated with severe PARDS (n = 9/29) with the highest quartile including >60% of the severe PARDS patients (test for trend, p  = 0.04). Higher total heparan sulfate and N- sulfated disaccharide levels were independently associated with fewer 28-day ventilator-free days in children with sepsis-associated PARDS (all p <  0.05)., Conclusions: Children with sepsis-associated PARDS exhibited higher plasma levels of heparan sulfate disaccharides and syndecan-1, suggesting that EGCX degradation biomarkers may provide insights into endothelial dysfunction and PARDS pathobiology., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Acute kidney injury is classified by urine output into non-oliguric and oliguric variants. Non-oliguric acute kidney injury has lower morbidity and mortality and accounts for up to 64% of acute kidney injury in hospitalized patients. However, the incidence of non-oliguric acute kidney injury in the trauma population and whether the 2 variants of acute kidney injury share the same risk factors is unknown. We hypothesized that oliguria would be present in the majority of acute kidney injury in severely injured trauma patients and that unique risk factors would predispose patients to the development of oliguria., Methods: Patients admitted to the trauma intensive care unit and diagnosed with an acute kidney injury between 2016 to 2021 were identified. Cases were categorized based on urine output into oliguric (<400 mL per day) and non-oliguric (>400 mL per day) disease. Risk factors, management, and outcomes were compared. Logistic regression was used to identify risk factors associated with oliguria., Results: A total of 227 patients met inclusion criteria. Non-oliguric acute kidney injury accounted for 74% of all cases and was associated with greater survival (78% vs 35.6%, P < .001). Using logistic regression, female sex, vasopressor use, and a greater net fluid balance at 48 hours were all predictive of oliguria (while controlling for age, race, shock index, massive transfusion, operative intervention, cardiac arrest, and nephrotoxic medication exposure)., Conclusion: Non-oliguria accounts for the majority of post-traumatic acute kidney injury and is associated with improved survival. Specific risk factors for the development of oliguric acute kidney injury include female sex, vasopressor use, and a higher net fluid balance at 48 hours., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen., Methods: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome., Results: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19)., Conclusion: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: The opioid epidemic in the United States continues to lead to a substantial number of preventable deaths and disability. The development of opioid dependence has been strongly linked to previous opioid exposure. Trauma patients are at particular risk since opioids are frequently required to control pain after injury. The purpose to this study was to examine the prevalence of opioid use before and after injury and to identify risk factors for persistent long-term opioid use after trauma., Methods: Records for all patients admitted to a Level 1 trauma center over a 1-year period were analyzed. Demographics, injury characteristics, and hospital course were recorded. A multistate Prescription Drug Monitoring Program database was queried to obtain records of all controlled substances prescribed from 6 months before the date of injury to 12 months after hospital discharge. Patients still receiving narcotics at 1 year were defined as persistent long-term users and were compared against those who were not., Results: A total of 2,992 patients were analyzed. Of all patients, 20.4% had filled a narcotic prescription within the 6 months before injury, 53.5% received opioids at hospital discharge, and 12.5% had persistent long-term use after trauma with the majority demonstrating preinjury use. Univariate risk factors for long-term use included female sex, longer length of stay, higher Injury Severity Score, anxiety, depression, orthopedic surgeries, spine injuries, multiple surgical locations, discharge to acute inpatient rehab, and preinjury opioid use. On multivariate analysis, the only significant predictors of persistent long-term prescription opioid use were preinjury use and a much smaller effect associated with use at discharge., Conclusion: During a sustained opioid epidemic, concerns and caution are warranted in the use of prescription narcotics for trauma patients. However, persistent long-term opioid use among opioid-naive patients is rare and difficult to predict after trauma., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 American Association for the Surgery of Trauma.)

Background: Unintentional firearm injury (UFI) remains a significant problem in the USA with respect to preventable injury and death. The antecedent, behaviour and consequence (ABC) taxonomy has been used by law enforcement agencies to evaluate unintentional firearm discharge. Using an adapted ABC taxonomy, we sought to categorise civilian UFI in our community to identify modifiable behaviours., Methods: Using a collaborative firearm injury database (containing both a university-based level 1 trauma registry and a metropolitan law enforcement database), all UFIs from August 2008 through December 2021 were identified. Perceived threat (antecedent), behaviour and injured party (consequence) were identified for each incident., Results: During the study period, 937 incidents of UFI were identified with 64.2% of incidents occurring during routine firearm tasks. 30.4% of UFI occurred during neglectful firearm behaviour such as inappropriate storage. Most injuries occurred under situations of low perceived threat. UFI involving children was most often due to inappropriate storage of weapons, while cleaning a firearm was the most common behaviour in adults. Overall, 16.5% of UFI involved injury to persons other than the one handling the weapon and approximately 1.3% of UFI resulted in mortality., Conclusions: The majority of UFI occurred during routine and expected firearm tasks such as firearm cleaning. Prevention programmes should not overlook these modifiable behaviours in an effort to reduce UFIs, complications and deaths., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children., Methods: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls., Results: GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p<0.001). FGF21 levels were mildly elevated in NASH and markedly elevated in MH (p<0.001). Both biomarkers were higher in patients with MH with a known genetic cause but were similar in acute and chronic presentations. Both markers had a strong performance to identify MH with a molecular diagnosis with the AUC for GDF15 0.93±0.04 and for FGF21 0.90±0.06. Simultaneous elevation of both markers >98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels <2000 ng/L predicting survival without liver transplantation (p<0.01)., Conclusions: GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Positron emission tomography (PET) scans are used in disease diagnosis and evaluation for pediatric oncology patients. Brown adipose tissue (BAT) 18 F-fluorodeoxyglucose-PET uptake is reported in 35% to 47% of pediatric patients. Several risk factors may be associated with BAT uptake., Objective: The aim was to determine the incidence and risk factors for BAT in pediatric patients using a consensus-based system and a novel grading scale., Methods: A total of 285 PET scans in 154 patients were retrospectively reviewed for the presence of BAT from September 2015 through December 2016. A consensus review was done by 2 radiologists, who graded BAT on a 0 to 3 scale and assessed its impact on PET interpretation., Results: The presence of moderate to severe BAT occurred in 11% of PET scans, and 6% of PETs had limited interpretation. Hodgkin lymphoma (n=53) patients had a 3.62-fold increased odds of moderate or severe BAT and a 6.59-fold increased odds of limited interpretation on PET imaging., Conclusion: The incidence of BAT was low but impacted radiologic interpretation when present. Further studies with a larger group of Hodgkin lymphoma patients are needed to explore the risk factors associated with moderate or severe BAT., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Compliant ectoparasiticide product use is a comprehensive way to control ticks and reduce the risk of tick-borne pathogen transmission to dogs. Because the systemically acting isoxazoline ectoparasiticides require tick attachment for drug delivery, fast speed of kill is essential to minimize tick-borne pathogen transmission risk., Methods: Dogs of satisfactory tick-carrying capacity were randomly allocated to treatment groups and administered, per label instructions, Bravecto ® Chews (minimum 25 mg/kg fluralaner), Simparica TRIO ® (minimum 1.2 mg/kg sarolaner, 24 µg/kg moxidectin, 5 mg/kg pyrantel), or no treatment. Dogs were infested with approximately 50 unfed adult (35 female, 15 male) Ixodes scapularis on Day -2, 21 and 28. Live tick counts were performed at 4, 8, 12 and 24 h post-treatment (Day 0) and post-infestation on Day 21 and 28. Tick control efficacy was determined by comparing live tick means for each product-treated group to the untreated control group and each other at all time points using a linear mixed model. The percent of dogs free of live ticks was analyzed using the Fisher's exact test for treatment group comparison., Results: The untreated control group maintained adequate tick infestations throughout the study. Using geometric means, an existing I. scapularis infestation was controlled by 99.7% and 93.0% 12 h post-treatment and by 100% and 99.5% 24 h post-treatment, for Bravecto ® and Simparica TRIO ® -treated dogs, respectively. Ixodes scapularis infestations were controlled more quickly for Bravecto ® - compared to Simparica TRIO ® -treated dogs on Day 21 at 8 h (efficacy 74.0% vs. 0.0%, p = 0.003) and 12 h (efficacy 99.2% vs. 39.4%, p < 0.001) post-infestation and Day 28 at 8 h (efficacy 92.2% vs. 0.0%, p < 0.001) and 12 h (efficacy 99.6% vs. 27.7%, p < 0.001) post-infestation. On Day 28 post-treatment, the efficacy of Bravecto ® and Simparica TRIO ® to control a new I. scapularis infestation was 100% and 96.6%, respectively, by 24 h post-infestation. Of product-treated dogs, 100% of Bravecto ® -treated dogs were free of live ticks by 24 h post-treatment or post-infestation. No treatment-related adverse reactions occurred during the study., Conclusions: Ixodes scapularis infestations are controlled more quickly 21 and 28 days post-treatment for dogs administered a single dose of Bravecto ® compared to dogs administered a single dose of Simparica TRIO ® ., (© 2023. The Author(s).)

Enterovirus D68 (EV-D68) causes cyclical outbreaks of respiratory disease and acute flaccid myelitis. EV-D68 is primarily transmitted through the respiratory route, but the duration of shedding in the respiratory tract is unknown. We prospectively enrolled 9 hospitalized children with EV-D68 respiratory infection and 16 household contacts to determine EV-D68 RNA shedding dynamics in the upper respiratory tract through serial midturbinate specimen collections and daily symptom diaries. Five (31.3%) household contacts, including 3 adults, were EV-D68-positive. The median duration of EV-D68 RNA shedding in the upper respiratory tract was 12 (range 7-15) days from symptom onset. The most common symptoms were nasal congestion (100%), cough (92.9%), difficulty breathing (78.6%), and wheezing (57.1%). The median illness duration was 20 (range 11-24) days. Understanding the duration of RNA shedding can inform the expected rate and timing of EV-D68 detection in associated acute flaccid myelitis cases and help guide public health measures.

Background: Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increased risk for treatment toxicity and adverse neurocognitive outcomes., Materials: The Human 660W-Quad v1.0 DNA BeadChip analysis (Illumina) was used to evaluate 1048 SNPs from 59 DNA repair genes in 46 subjects. IQ testing was measured by the Wechsler Intelligence Scale for Children. Linear regression was used to identify the 10 SNPs with the strongest association with IQ scores while adjusting for radiation type., Results: The low vs high IQ patient cohorts were well matched for time from first treatment to most recent IQ, first treatment age, sex, and treatments received. 5 SNPs on 3 different genes (CYP29, XRCC1, and BRCA1) and on 3 different chromosomes (10, 19, and 17) had the strongest association with most recent IQ score that was not modified by radiation type. Furthermore, 5 SNPs on 4 different genes (WRN, NR3C1, ERCC4, RAD51L1) on 4 different chromosomes (8, 5, 16, 14) had the strongest association with change in IQ independent of radiation type, first IQ, and years between IQ measures., Conclusions: SNPs offer the potential to predict adverse neurocognitive outcomes in pediatric brain tumor survivors. Our results require validation in a larger patient cohort. Improving the ability to identify children at risk of treatment related neurocognitive deficits could allow for better treatment stratification and early cognitive interventions., (© 2023. The Author(s).)

Background: Unplanned extubations (UEs) in injured patients are potentially fatal, but etiology and patient characteristics are not well described. We have been prospectively characterizing the etiology of UEs after we identified a high rate of UEs and implemented an educational program to address it. This period of monitoring included the years of the COVID-19 pandemic that produced high rates of workforce turnover in many hospitals, dramatically affecting nursing and respiratory therapy services. We hypothesized that frequency of UEs would depend on the etiology and that the workforce changes produced by the COVID-19 pandemic would increase UEs., Methods: This study was a prospective tracking and retrospective review of trauma registry and performance improvement data from 2012-2021., Results: UE subjects were younger, were more frequently male, were diagnosed more frequently with pneumonia (38% vs 27%), and had longer hospital (19 d vs 15 d) and ICU length of stay (LOS) (12 d vs 10 d) (all P < .05). Most UEs were due to patient factors (self-extubation) that decreased after education, while UEs from other etiologies (mechanical, provider) were stable. Subjects with UEs from mechanical or provider etiologies had longer ICU LOS, higher mortality, and were less likely to be discharged home. The COVID-19 pandemic was associated with more total patient admissions and more days of ventilator use, but the rate of UEs was not changed., Conclusions: UEs were decreased by education with ongoing tracking, and UEs from patient factors were associated with better outcome than other etiologies. Workforce changes produced by the COVID-19 pandemic did not change the rate of UEs., (Copyright © 2023 by Daedalus Enterprises.)

Phenol-soluble modulins (PSMs) are the primary proteinaceous component of Staphylococcus aureus biofilms. Residence in the protective environment of biofilms allows bacteria to rapidly evolve and acquire antimicrobial resistance, which can lead to persistent infections such as those caused by methicillin-resistant S. aureus (MRSA). In their soluble form, PSMs hinder the immune response of the host and can increase the virulence potential of MRSA. PSMs also self-assemble into insoluble functional amyloids that contribute to the structural scaffold of biofilms. The specific roles of PSM peptides in biofilms remain poorly understood. Here, we report the development of a genetically tractable yeast model system for studying the properties of PSMα peptides. Expression of PSMα peptides in yeast drives the formation of toxic insoluble aggregates that adopt vesicle-like structures. Using this system, we probed the molecular drivers of PSMα aggregation to delineate key similarities and differences among the PSMs and identified a crucial residue that drives PSM features. Biofilms are a major public health threat; thus, biofilm disruption is a key goal. To solubilize aggregates comprised of a diverse range of amyloid and amyloid-like species, we have developed engineered variants of Hsp104, a hexameric AAA+ protein disaggregase from yeast. Here, we demonstrate that potentiated Hsp104 variants counter the toxicity and aggregation of PSMα peptides. Further, we demonstrate that a potentiated Hsp104 variant can drive the disassembly of preformed S. aureus biofilms. We suggest that this new yeast model can be a powerful platform for screening for agents that disrupt PSM aggregation and that Hsp104 disaggregases could be a promising tool for the safe enzymatic disruption of biofilms. IMPORTANCE Biofilms are complex mixtures secreted by bacteria that form a material in which the bacteria can become embedded. This process transforms the properties of the bacteria, and they become more resistant to removal, which can give rise to multidrug-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA). Here, we study phenol-soluble modulins (PSMs), which are amyloidogenic proteins secreted by S. aureus, that become incorporated into biofilms. Biofilms are challenging to study, so we have developed a new genetically tractable yeast model to study the PSMs. We used our system to learn about several key features of the PSMs. We also demonstrate that variants of an amyloid disaggregase, Hsp104, can disrupt the PSMs and, more importantly, dissolve preformed S. aureus biofilms. We propose that our system can be a powerful screening tool and that Hsp104 disaggregases may be a new avenue to explore for biofilm disruption agents., Competing Interests: The authors declare no conflict of interest.

The TREM2-DAP12 receptor complex sustains microglia functions. Heterozygous hypofunctional TREM2 variants impair microglia, accelerating late-onset Alzheimer's disease. Homozygous inactivating variants of TREM2 or TYROBP-encoding DAP12 cause Nasu-Hakola disease (NHD), an early-onset dementia characterized by cerebral atrophy, myelin loss and gliosis. Mechanisms underpinning NHD are unknown. Here, single-nucleus RNA-sequencing analysis of brain specimens from DAP12-deficient NHD individuals revealed a unique microglia signature indicating heightened RUNX1, STAT3 and transforming growth factor-β signaling pathways that mediate repair responses to injuries. This profile correlated with a wound healing signature in astrocytes and impaired myelination in oligodendrocytes, while pericyte profiles indicated vascular abnormalities. Conversely, single-nuclei signatures in mice lacking DAP12 signaling reflected very mild microglial defects that did not recapitulate NHD. We envision that DAP12 signaling in microglia attenuates wound healing pathways that, if left unchecked, interfere with microglial physiological functions, causing pathology in human. The identification of a dysregulated NHD microglia signature sparks potential therapeutic strategies aimed at resetting microglia signaling pathways., (© 2023. Springer Nature America, Inc.)

Background: The COVID-19 pandemic has altered daily life on a global scale and has resulted in significant mortality with &gt;985,000 lives lost in the United States alone. Superimposed on the COVID-19 pandemic has been a concurrent worsening of longstanding urban gun violence. We sought to evaluate the impact attributable to these 2 major public health issues on the greater Louisville region as determined by years of potential life lost., Methods: Using the Collaborative Jefferson County Firearm Injury Database, all firearm injuries from January 1, 2011 to December 31, 2021 were examined. The COVID-19 data was compiled from the Louisville Metro Department of Public Health and Wellness. Pre-COVID (March 1, 2019-February 29, 2020) and COVID (March 1, 2020-February 28, 2021) time intervals were examined. The demographics, outcomes data, and years of potential life lost were determined for the groups, and injury locations were geocoded., Results: From 2011 to 2021, there were 6,043 firearm injuries in Jefferson County, Kentucky. During the COVID time interval, there were 4,574 years of potential life lost due to the SARS-CoV-2 virus and 9,722 years of potential life lost due to all-cause gun violence. In the pre-COVID time interval, there were 5,723 years of potential life lost due to all-cause gun violence., Conclusion: In Louisville, greater years of potential life lost were attributable to firearm fatalities than the SARS-CoV-2 virus. Given the impact of COVID-19, the robust response has been proportionate and appropriate. The lack of response to firearm injury and fatality is striking in comparison. Additional resources to combat the sequelae of gun violence are needed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose : The Breastfeeding Relationship Scale (BFRS) was developed to measure mother-infant mutual responsiveness during breastfeeding. The purpose of this study was to develop and test the psychometric properties of the BFRS. Methods : Construct validity of a 16-item three-factor model (Mother-Infant Breastfeeding Interaction, Perceived Adequate Milk Supply, and Breastfeeding Synchronicity) was assessed using confirmatory factor analysis (CFA) and reliability (Cronbach's alpha) across two independent samples. Results : CFA of the hypothesized three-factor model demonstrated good fit in both samples (comparative fit index >.90, root mean square error of approximation <.06, square root mean residual < .061). Cronbach's alpha for the constructs ranged between .73 and .83. Conclusion : The BFRS is a valid measure of breastfeeding relations between mother and infant. Reliability was acceptable for all constructs in both samples., (© Copyright 2022 Springer Publishing Company, LLC.)

Purpose: Neuroendocrine neoplasms (NENs) of the gallbladder are very rare. As a result, the classification of pathologic specimens from gallbladder NENs, currently classified as gallbladder neuroendocrine tumors (GB-NETs) and carcinomas (GB-NECs), is inconsistent and makes nomenclature, classification, and management difficult. Our study aims to evaluate the epidemiological trend, tumor biology, and outcomes of GB-NET and GB-NEC over the last 5 decades., Methods: This is a retrospective analysis of the SEER database from 1973 to 2016. The epidemiological trend was analyzed using the age-adjusted Joinpoint regression analysis. Survival was assessed with Kaplan-Meier analysis and Cox regression was used to assess predictors of poor survival., Results: A total of 482 patients with GB-NEN were identified. Mean age at diagnosis was 65.2 ± 14.3 years. Females outnumbered males (65.6% vs. 34.4%). The Joinpoint nationwide trend analysis showed a 7% increase per year from 1973 to 2016. The mean survival time after diagnosis of GB-NEN was 37.11 ± 55.3 months. The most common pattern of nodal distribution was N0 (50.2%) followed by N1 (30.9%) and N2 (19.2%). Advanced tumor spread (into the liver, regional, and distant metastasis) was seen in 60.3% of patients. Patients who underwent surgery had a significant survival advantage (111.0 ± 8.3 vs. 8.3 ± 1.2 months, p < 0.01). Cox regression analysis showed advanced age (p < 0.01), tumor stage (P < 0.01), tumor extension (p < 0.01), and histopathologic grade (p < 0.01) were associated with higher mortality., Conclusion: Gallbladder NENs are a rare histopathological variant of gallbladder cancer that is showing a rising incidence in the USA. In addition to tumor staging, surgical resection significantly impacts patient survival, when patients are able to undergo surgery irrespective of tumor staging. Advanced age, tumor extension, and histopathological grade of the tumor were associated with higher mortality., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Current data on the epidemiology of firearm injury in the United States are incomplete. Common sources include hospital, law enforcement, consumer, and public health databases, but each database has limitations that exclude injury subgroups. By integrating hospital (inpatient and outpatient) and law enforcement databases, we hypothesized that a more accurate depiction of the totality of firearm injury in our region could be achieved., Methods: We constructed a collaborative firearm injury database consisting of all patients admitted as inpatients to the regional level 1 trauma hospital (inpatient registry), patients treated and released from the emergency department (ED), and subjects encountering local law enforcement as a result of firearm injury in Jefferson County, Kentucky. Injuries recorded from January 1, 2016, to December 31, 2020, were analyzed. Outcomes, demographics, and injury detection rates from individual databases were compared with those of the combined collaborative database and compared using χ2 testing across databases., Results: The inpatient registry (n = 1,441) and ED database (n = 1,109) were combined, resulting in 2,550 incidents in the hospital database. The law enforcement database consisted of 2,665 patient incidents, with 2,008 incidents in common with the hospital database and 657 unique incidents. The merged collaborative database consisted of 3,207 incidents. In comparison with the collaborative database, the inpatient, total hospital (inpatient and ED), and law enforcement databases failed to include 55%, 20%, and 17% of all injuries, respectively. The hospital captured nearly 94% of survivors but less than 40% of nonsurvivors. Law enforcement captured 93% of nonsurvivors but missed 20% of survivors. Mortality (11-26%) and injury incidence were markedly different across the databases., Discussion: The utilization of trauma registry or law enforcement databases alone do not accurately reflect the epidemiology of firearm injury and may misrepresent areas in need of greater injury prevention efforts., Level of Evidence: Epidemiological, level IV., (Copyright © 2021 American Association for the Surgery of Trauma.)

Purpose of Review: Food insecurity and gun violence are timely and relevant public health issues impacting many regions within the USA with a potential association. Terminology surrounding food access and food security can be confusing, which is important to understand when examining the relationship between these issues and gun violence., Recent Findings: Food insecurity is an individual level risk factor that appears to correlate with an increased rate of exposure and future involvement in violence. Food deserts represent geographic regions with limited access to food but do not necessarily represent regions with high prevalence of food insecurity. Although both food insecurity and food deserts in urban regions have been linked with increased incidence of gun violence, a high prevalence of food insecurity was found to be more predictive. A high prevalence of food insecurity in urban regions likely serves as a marker for socioeconomic disadvantage and intentional disinvestment. These regions are predictably associated with a higher incidence of interpersonal gun violence. Food deserts in rural areas have not, to date, been shown to correlate with interpersonal gun violence. Urban food insecurity and gun violence are both likely the byproduct of structural violence. Despite the significant overlap and similar contributors, the application of the public health framework in addressing these two issues has historically been quite different., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Many operations for complications after bariatric surgery are performed by surgeons without bariatric expertise at centers without teams who routinely care for bariatric patients. This study sought to evaluate whether bariatric expertise affects patterns of care and perioperative outcomes among patients undergoing operative intervention for complications after bariatric surgery., Methods: Administrative claims data from the Kentucky Office of Health Policy were queried for inpatients undergoing operative intervention for complications related to bariatric surgery between 2015 and 2018. Patients were stratified with respect to whether or not they underwent surgery at a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) accredited bariatric surgery center (BCE) or not (non-BCE). Groups were compared with respect to demographic, procedural, and outcome variables., Results: BCE patients were more often Caucasian than non-BCE patients (p < 0.001) and have either private insurance or Medicare coverage (p = 0.02). Regarding operative approach, operations were more likely to be performed laparoscopically in BCE (88.5% BCE vs. 80.9% non-BCE, p = 0.007). Length of stay was significantly shorter for BCE patients (median 2 days BCE vs. 3 days non-BCE, p < 0.001), and BCE patients were more likely to be discharged home (85.4% BCE vs. 78.5% non-BCE, p = 0.02). Inpatient mortality and average total charges per patient did not differ significantly between the two groups CONCLUSIONS: Surgical management of complications after bariatric surgery at BCE is associated with greater utilization of minimally invasive techniques, shorter hospital stay, and increased likelihood of routine home discharge. These findings should prompt a review and standardization of care patterns for patients with complications after bariatric surgery aimed at optimizing outcomes and improving value.

Paediatric cancers commonly harbour quiet mutational landscapes and are instead characterized by single driver events such as the mutation of critical chromatin regulators, expression of oncohistones, or expression of oncogenic fusion proteins. These events ultimately promote malignancy through disruption of normal gene regulation and development. The driver protein in Ewing sarcoma, EWS/FLI, is an oncogenic fusion and transcription factor that reshapes the enhancer landscape, resulting in widespread transcriptional dysregulation. Lysine-specific demethylase 1 (LSD1) is a critical functional partner for EWS/FLI as inhibition of LSD1 reverses the transcriptional activity of EWS/FLI. However, how LSD1 participates in fusion-directed epigenomic regulation and aberrant gene activation is unknown. We now show EWS/FLI causes dynamic rearrangement of LSD1 and we uncover a role for LSD1 in gene activation through colocalization at EWS/FLI binding sites throughout the genome. LSD1 is integral to the establishment of Ewing sarcoma super-enhancers at GGAA-microsatellites, which ubiquitously overlap non-microsatellite loci bound by EWS/FLI. Together, we show that EWS/FLI induces widespread changes to LSD1 distribution in a process that impacts the enhancer landscape throughout the genome.