Pediatric Homicides: Not Just a Teenage Problem.

INTRODUCTION: Homicide is a leading cause of death for American children. We hypothesized demographics and homicide circumstances would differ by victim age. METHODS: We performed a retrospective analysis of the 2003-2020 National Violent Death Reporting System. The National Violent Death Reporting System collects data from nearly all 50 states, the District of Columbia, and Puerto Rico. Demographics (age, sex, race, and ethnicity), homicide year, and weapon type were abstracted. Inclusion criteria were pediatric victims (age < 18). Two groups: 0-4 y old (young cohort [YC]) and 13-17 y old (teen cohort [TC]) were compared. Chi-squared tests, p-test, and t-tests with significance P < 0.05 were used to determine the association between victim demographics, cohort, and homicide mechanism. RESULTS: 10,569 pediatric (male: 70.2% [n = 7424], median age: 12 y old [interquartile range 1-16], black: 52.7% [n = 5573]) homicides met inclusion. Homicides demonstrated a bimodal age distribution (YC: 40.9% [n = 4320] versus TC: 48.9% [n = 5164]). Gender and race were both associated with homicide victimhood (P < 0.001). TC homicides were more likely to be male (YC: 57.8% [n = 2496] versus TC: 83.7% [n = 4320], P < 0.001) and black (YC: 40.1% [n = 1730] versus TC: 65.0% [n = 3357], P < 0.001). Pediatric homicides increased from 2018 (n = 1049) to 2020 (n = 1597), with only TC demonstrating a significant increase (2018: n = 522 versus 2020: n = 971, P < 0.001). Homicide mechanism was significantly associated with age (Blunt: YC: 57.5% [n = 2484] versus TC: 2.9% [n = 148], P < 0.001; Penetrating: YC: 7.9% [n = 340] versus TC: 92.8% [n = 4794], P < 0.001). CONCLUSIONS: Pediatric homicides demonstrate distinct demographic characteristics and homicide mechanisms between two at risk age cohorts. Age-based education and intervention strategies may increase injury prevention programs' efficacy.

An Academic-Community Partnership to Address Gun Violence in the Roseland Neighborhood of Chicago.

BACKGROUND AND OBJECTIVES: Gun violence is the leading cause of death for youth. This study examined an academic-community partnership to address gun violence through a strength-based approach called Asset-Based Community Development. METHODS: We used a case study design. Participants were Black youth who encounter frequent gun violence (average age = 16.7 years; 72% male). Our partnership involved survey development/completion and semistructured discussions. We also interviewed community stakeholders to collect data on local assets. We interpreted data through a communitywide forum to guide social action to address gun violence. RESULTS: The majority of youth (76%) witnessed neighborhood violence in the last year. The top youth concerns related to gun violence included poverty, guns, and gangs. Community stakeholders saw local people and local organizations as primary community assets. A community forum to interpret these data led to social action in the form of an environmental strategy-cleaning up an unused commercial building for the development of a youth tech center. The majority of youth participants (89.5%) agreed or strongly agreed that they had a voice in the research process. CONCLUSION: Participatory research that takes an asset-based approach can enable relevant inquiry that engages youth and guides social action to address gun violence.

Treatment of cerebrotendinous xanthomatosis in pregnancy: Patient and physician perspectives.

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive disorder of bile acid synthesis that presents with varied and progressive symptomology. Early treatment with chenodeoxycholic acid (CDCA) improves symptoms and slows degeneration. Patients with CTX are commonly recommended to discontinue CDCA treatment during pregnancy because of theoretical risks to the fetus, but patient and clinician concerns about the risks of stopping treatment cause uncertainty. Herein, we report the experiences and perspectives of two women with CTX from the time of diagnosis through pregnancy, as well as decisions regarding CDCA treatment during pregnancy. Before becoming pregnant, both women were concerned about potential risks to their newborns if they continued or stopped CDCA treatment during pregnancy. Reassurance from their CTX specialist was the primary factor in their decision to continue treatment during pregnancy. After pregnancies complicated by preeclampsia, one gave birth to a healthy infant and the other gave birth to an infant later diagnosed with periventricular leukomalacia. Neither experienced CDCA-related complications.

A 43-Day-Old Male With Respiratory Distress and Acute-Onset Hypotonia.

A 43-day-old, full-term, previously healthy male presented with decreased activity and oral intake. He was found to be grunting and hypoxemic on examination, and a respiratory pathogen panel was positive for rhinovirus. He was diagnosed with presumed bronchiolitis. His neurologic exam on admission was normal. Because of respiratory failure, he was escalated from high-flow nasal cannula to bilevel positive airway pressure upon admission and he was started on ceftriaxone and vancomycin while awaiting culture data. On hospital day 6, he required escalation of respiratory support. His examination at that time was notable for new hypotonia of his bilateral upper and lower extremities, sluggish pupils, bilateral exotropia, intermittent vertical nystagmus, and an absent Moro reflex. He developed a focal seizure and a computed tomography of the brain demonstrated simple right otomastoiditis. The seizure was attributed to a serum sodium of 113 mmol/L in the setting of syndrome of inappropriate antidiuretic hormone secretion, thought to be secondary to viral bronchiolitis. However, as the patient's sodium was corrected to a normal range, he continued to have neurologic deficits on examination. Given his persistent hypotonia and respiratory failure, atypical for the expected course of viral bronchiolitis, the patient underwent an extensive neurologic and infectious workup, which ultimately revealed a surprising diagnosis.

Evaluation of Injury Severity and Resource Utilization in Pediatric Firearm and Sharp Force Injuries.

Importance: Pediatric firearm injuries are a serious and growing public health problem, constituting the second leading cause of death in children and adolescents in the United States. Firearm injuries have a high case fatality, but knowledge is limited to date regarding their injury severity and health care utilization burden compared with those of other penetrating injuries, especially among children with critical injury. Objective: To describe and compare the resource utilization, injury severity, and short-term clinical outcomes associated with pediatric firearm injuries and other penetrating trauma. Design, Setting, and Participants: This retrospective cohort study used data from the National Trauma Data Bank, an encounter-level registry of trauma data in the United States, from January 1, 2007, to December 31, 2016. Encounters for firearm injury (n = 25 155) or cut or pierce injury (21 270) in children 17 years or younger were analyzed. Statistical analysis was conducted from July 15, 2018, to June 5, 2019. Exposures: Firearm injury compared with cut or pierce injury encounters. Main Outcomes and Measures: Intensive care unit (ICU) admission, hospital and ICU length of stay (LOS), and Injury Severity Score (ISS). Results: A total of 25 155 firearm injury encounters and 21 270 cut or pierce injury encounters were analyzed. Most firearm and cut or pierce injuries occurred among boys (21 573 [85.8%] and 15 864 [74.6%]) and adolescents aged 15 to 17 years (18 807 [74.8%] and 10 895 [51.2%]). A greater proportion of those with firearm injuries were African American children compared with those with cut or pierce injuries (15 019 [61.3%] vs 6397 [31.2%]). A greater proportion of those with firearm injuries compared with cut or pierce injuries were admitted to the ICU (7682 [30.5%] vs 2712 [12.8%]). Compared with cut or pierce injuries, firearm injuries were associated with a higher mean (SD) ISS (4.6 [6.8] vs 10.9 [12.7] points), longer mean (SD) hospital LOS (2.8 [4.1] vs 5.0 [8.4] days), and longer mean (SD) ICU LOS (3.1 [4.5] vs 5.1 [7.7] days). Firearm injuries accounted for 126 027 hospital days and 39 255 ICU days, whereas cut or pierce injuries accounted for 58 705 hospital days and 8353 ICU days. After adjustments for age, sex, year, and hospital, those with firearm injuries were more likely to require ICU admission (relative risk [RR], 2.3; 95% CI, 2.1-2.5; P < .001) and to have higher ISS scores (6.7 points higher for all injuries; 95% CI, 6.1-7.2) compared with those with cut or pierce injuries, even among critical injuries. Multinomial logistic regression demonstrated higher risk of prolonged hospital LOS (RR ratio, 4.11; 95% CI, 3.46-4.89; P < .001) and ICU LOS (RR ratio, 2.2; 95% CI, 1.9-2.3) for firearm injuries compared with cut or pierce injuries. Conclusions and Relevance: This study found that pediatric firearm injuries were associated with greater severity and health care utilization compared with penetrating trauma from other mechanisms, suggesting that the mechanism of injury is an important consideration in penetrating sharp force trauma in children and adolescents. Public health measures, legislative efforts, and safe storage practices are among the interventions needed to reduce pediatric firearm injuries.

Bioremediation of a Common Product of Food Processing by a Human Gut Bacterium.

Dramatic increases in processed food consumption represent a global health threat. Maillard reaction products (MRPs), which are common in processed foods, form upon heat-induced reaction of amino acids with reducing sugars and include advanced glycation end products with deleterious health effects. To examine how processed foods affect the microbiota, we fed gnotobiotic mice, colonized with 54 phylogenetically diverse human gut bacterial strains, defined sugar-rich diets containing whey as the protein source or a matched amino acid mixture. Whey or ϵ-fructoselysine, an MRP in whey and many processed foods, selectively increases Collinsella intestinalis absolute abundance and induces Collinsella expression of genomic loci directing import and metabolism of ϵ-fructoselysine to innocuous products. This locus is repressed by glucose in C. aerofaciens, whose abundance decreases with whey, but is not repressed in C. intestinalis. Identifying gut organisms responding to and degrading potentially harmful processed food components has implications for food science, microbiome science, and public health.

Pediatric Acute Myocarditis: Predicting Hemodynamic Compromise at Presentation to Health Care.

BACKGROUND: The clinical spectrum of pediatric acute myocarditis ranges from minimal symptoms with intact hemodynamics to rapid cardiovascular collapse and death. We sought to identify factors on initial presentation associated with subsequent hemodynamic compromise. METHODS: We performed a retrospective cohort study of patients with acute myocarditis at a freestanding pediatric hospital from 2007 to 2016. We defined 2 cohorts: high-acuity patients with hemodynamic compromise defined as requiring inotropic or vasoactive medications, cardiopulmonary resuscitation, extracorporeal membrane oxygenation, ventricular assist devices, or transplant or who died and low-acuity patients without these interventions. We collected the first recorded set of vital signs, symptoms, laboratory values, and chest radiograph, electrocardiogram, and echocardiography results. Univariate analysis was performed, and 2 multivariable logistic regression models were created to discriminate between cohorts. RESULTS: A total of 74 patients were included: 33 high acuity and 41 low acuity. There were significant differences in demographics, symptoms, and physical examination, laboratory, electrocardiogram, and echocardiography findings between high- and low-acuity cohorts. Multivariable logistic regression models were highly discriminate in predicting those in the high-acuity cohort. The first model included presence of tachycardia, tachypnea, creatinine, and cardiomegaly on chest radiograph (area under the curve = 0.913). The second model added the presence of pericardial effusion to the above variables (area under the curve = 0.964). CONCLUSIONS: Models based on factors available at initial presentation with acute myocarditis are predictive of subsequent hemodynamic compromise. If our results can be validated in a multicenter study, these models may help disposition patients with suspected acute myocarditis (with those who meet model criteria being admitted to centers capable of rapidly providing extracorporeal membrane oxygenation, ventricular assist devices, and heart transplant evaluation).

Attenuated Effects of Bile Acids on Glucose Metabolism and Insulin Sensitivity in a Male Mouse Model of Prenatal Undernutrition.

Prenatal undernutrition and low birth weight are associated with risk of type 2 diabetes and obesity. Prenatal caloric restriction results in low birth weight, glucose intolerance, obesity, and reduced plasma bile acids (BAs) in offspring mice. Because BAs can regulate systemic metabolism and glucose homeostasis, we hypothesized that BA supplementation could prevent diet-induced obesity and glucose intolerance in this model of developmental programming. Pregnant dams were food restricted by 50% from gestational days 12.5 to 18.5. Offspring of both undernourished (UN) and control (C) dams given unrestricted diets were weaned to high-fat diets with or without supplementation with 0.25% w/w ursodeoxycholic acid (UDCA), yielding four experimental groups: C, UN, C + UDCA, and UN + UDCA. Glucose homeostasis, BA composition, liver and intestinal gene expression, and microbiota composition were analyzed in the four groups. Although UDCA supplementation ameliorated diet-induced obesity in C mice, there was no effect in UN mice. UDCA similarly lowered fasting insulin, and improved glucose tolerance, pyruvate tolerance, and liver steatosis in C, but not UN, animals. BA composition differed significantly, and liver and ileal expression of genes involved in BA metabolism (Cyp7b1, Shp) were differentially induced by UDCA in C vs UN animals. Bacterial taxa in fecal microbiota correlated with treatment groups and metabolic parameters. In conclusion, prenatal undernutrition alters responsiveness to the metabolic benefits of BA supplementation, with resistance to the weight-lowering and insulin-sensitizing effects of UDCA supplementation. Our findings suggest that BA metabolism may be a previously unrecognized contributor to developmentally programmed diabetes risk.

Functional genomic analysis of human mitochondrial RNA processing.

Both strands of human mtDNA are transcribed in continuous, multigenic units that are cleaved into the mature rRNAs, tRNAs, and mRNAs required for respiratory chain biogenesis. We sought to systematically identify nuclear-encoded proteins that contribute to processing of mtRNAs within the organelle. First, we devised and validated a multiplex MitoString assay that quantitates 27 mature and precursor mtDNA transcripts. Second, we applied MitoString profiling to evaluate the impact of silencing each of 107 mitochondrial-localized, predicted RNA-binding proteins. With the resulting data set, we rediscovered the roles of recently identified RNA-processing enzymes, detected unanticipated roles of known disease genes in RNA processing, and identified new regulatory factors. We demonstrate that one such factor, FASTKD4, modulates the half-lives of a subset of mt-mRNAs and associates with mtRNAs in vivo. MitoString profiling may be useful for diagnosing and deciphering the pathogenesis of mtDNA disorders.

A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs.

BACKGROUND: Mounting evidence suggests a major role for epigenetic feedback in Plasmodium falciparum transcriptional regulation. Long non-coding RNAs (lncRNAs) have recently emerged as a new paradigm in epigenetic remodeling. We therefore set out to investigate putative roles for lncRNAs in P. falciparum transcriptional regulation. RESULTS: We used a high-resolution DNA tiling microarray to survey transcriptional activity across 22.6% of the P. falciparum strain 3D7 genome. We identified 872 protein-coding genes and 60 putative P. falciparum lncRNAs under developmental regulation during the parasite's pathogenic human blood stage. Further characterization of lncRNA candidates led to the discovery of an intriguing family of lncRNA telomere-associated repetitive element transcripts, termed lncRNA-TARE. We have quantified lncRNA-TARE expression at 15 distinct chromosome ends and mapped putative transcriptional start and termination sites of lncRNA-TARE loci. Remarkably, we observed coordinated and stage-specific expression of lncRNA-TARE on all chromosome ends tested, and two dominant transcripts of approximately 1.5 kb and 3.1 kb transcribed towards the telomere. CONCLUSIONS: We have characterized a family of 22 telomere-associated lncRNAs in P. falciparum. Homologous lncRNA-TARE loci are coordinately expressed after parasite DNA replication, and are poised to play an important role in P. falciparum telomere maintenance, virulence gene regulation, and potentially other processes of parasite chromosome end biology. Further study of lncRNA-TARE and other promising lncRNA candidates may provide mechanistic insight into P. falciparum transcriptional regulation.