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The objective of the paper is to analyze the importance of institutional changes in the financial system for the efficacy of monetary policy and in particular for the connection between the balance of payments (capital account) and monetary policy. Particular institutional developments studied include the emergence of certificates of deposit and the removal of interest rate ceilings in 1973. The result established, using a general equilibrium model, is that the degree to which transactions in the capital account of the balance of payments offset a domestic monetary expansion is greater in a regime of market-determined interest rates than in a regime of administered rates. [ABSTRACT FROM AUTHOR]

Background: As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC).Methods: In a national study, we compared the characteristics of patients with fatal cases of EVALI with those of patients with nonfatal cases to improve the ability of clinicians to identify patients at increased risk for death from the condition. Health departments reported cases of EVALI to the CDC and included, when available, data from medical-record abstractions and patient interviews. Analyses included all the patients with fatal or nonfatal cases of EVALI that were reported to the CDC as of January 7, 2020. We also present three case reports of patients who died from EVALI to illustrate the clinical characteristics common among such patients.Results: Most of the patients with fatal or nonfatal cases of EVALI were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively). The proportion of patients with fatal or nonfatal cases was higher among those who were non-Hispanic white (39 of 49 [80%] and 1104 of 1818 [61%], respectively) than among those in other race or ethnic groups. The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]). Among the patients who had an available medical history, a higher proportion of those with fatal cases than those with nonfatal cases had a history of asthma (13 of 57 [23%] vs. 102 of 1297 [8%]), cardiac disease (26 of 55 [47%] vs. 115 of 1169 [10%]), or a mental health condition (32 of 49 [65%] vs. 575 of 1398 [41%]). A total of 26 of 50 patients (52%) with fatal cases had obesity. Half the patients with fatal cases (25 of 54 [46%]) were seen in an outpatient setting before hospitalization or death.Conclusions: Chronic conditions, including cardiac and respiratory diseases and mental health conditions, were common among hospitalized patients with EVALI. [ABSTRACT FROM AUTHOR]

Importance: Recreational use of drug-soaked paper strips (hereafter, strips) in correctional facilities poses a major public health risk owing to the diverse and potentially severe toxic effects of the substances they contain. Understanding the clinical manifestations and outcomes of exposure to these strips is important for developing effective management and prevention strategies., Objective: To characterize the clinical manifestations, management, and outcomes of intoxication from strips in a correctional facility population, and to identify the specific substances present in these strips., Design, Setting, and Participants: This is a case series with a retrospective medical record review and biospecimen analysis. Participants were incarcerated individuals from a county jail who presented to the emergency department of an urban hospital in Atlanta, Georgia, with suspected strip exposure between August 1, 2022, and November 1, 2023. Strip samples were tested using gas chromatography-mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), and serum samples were analyzed via LC-QTOF-MS., Exposures: All patients had suspected exposure to strips, thought to contain opioids, synthetic cannabinoid receptor agonists (SCRAs), and other novel synthetic drugs., Main Outcomes and Measures: The primary outcomes were clinical manifestations of strip exposure, including clinical signs and symptoms, vital sign derangements, laboratory and imaging findings, treatments administered, and patient outcomes., Results: There were 18 patients (all male; median [IQR] age, 27.5 [18.0-45.0] years) in total. Bradycardia (11 patients [61%]) and central nervous system depression (17 patients [94%]) were the most common clinical findings. Other symptoms included agitation (6 patients [33%]) and seizures (4 patients [22%]). Treatment primarily involved supportive care, with 2 patients requiring intubation. One patient died as a result of hypoxic ischemic encephalopathy. Analysis of strip samples revealed the presence of synthetic cannabinoids and benzimidazole opioids, but no household cleaners or pesticides. Serum testing confirmed the presence of SCRAs and their metabolites., Conclusions and Relevance: In this case series study of strip intoxication among incarcerated individuals, severe and variable clinical manifestations were observed, predominantly associated with their SCRA content. Bradycardia in the context of major central nervous system depression was an indicator of severe SCRA toxic effects. Further research is needed to better understand strip use and to develop effective prevention and treatment strategies.

Purpose: Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial., Methods: We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction., Results: Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen's Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) ( p-value-for-interaction = 0.03)., Conclusion: Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.

Background: The cerebellum is a key structure involved in balance and motor control, and has become a new stimulation target in brain regulation technology. Interference theta-burst simulation (iTBS) is a novel simulation mode of repetitive transcranial magnetic simulation. However, the impact of cerebellar iTBS on balance function and gait in stroke patients is still unknown., Aim: The aim of this study was to determine whether cerebellar iTBS can improve function, particularly balance and gait, in patients with post-stroke hemiplegia., Design: This study is a randomized, double-blind, sham controlled clinical trial., Setting: The study was carried out at the Department of Rehabilitation Medicine in a general hospital., Population: Patients with stroke with first unilateral lesions were enrolled in the study., Methods: Thirty-six patients were randomly assigned to the cerebellar iTBS group or sham stimulation group. The cerebellar iTBS or pseudo stimulation site is the ipsilateral cerebellum on the paralyzed side, which is completed just before daily physical therapy. The study was conducted five times a week for two consecutive weeks. All patients were assessed before the intervention (T0) and at the end of 2 weeks of treatment (T1), respectively. The primary outcome was the Berg Balance Scale (BBS), while secondary outcome measures included the Fugl Meyer Lower Limb Assessment Scale (FMA-LE), timed up and go (TUG), Barthel Index (BI), and gait analysis., Results: After 2 weeks of intervention, the BBS, FMA-LE, TUG, and BI score in both the iTBS group and the sham group were significantly improved compared to the baseline (all P<0.05). Also, there was a significant gait parameter improvement including the cadence, stride length, velocity, step length compared to the baseline (P<0.05) in the iTBS group, but only significant improvement in cadence was identified in the sham group (P<0.05). Intergroup comparison showed that the BBS (P<0.001), FMA-LE (P<0.001), and BI (P=0.002) in the iTBS group were significantly higher than those in the sham group, and the TUG in the iTBS was significantly lower than that in the sham group (P=0.002). In addition, there were significant differences in cadence (P=0.029), strip length (P=0.046), gain velocity (P=0.002), and step length of affected lower limb (P=0.024) between the iTBS group and the sham iTBS group., Conclusions: Physical therapy is able to improve the functional recovery in hemiplegic patients after stroke, but the cerebellar iTBS can facilitate and accelerate the recovery, particularly the balance function and gait. Cerebellar iTBS could be an efficient and facilitative treatment for patients with stroke., Clinical Rehabilitation Impact: Cerebellar iTBS provides a convenient and efficient treatment modality for functional recovery of patients with stroke, especially balance function and gait.

Liquid biopsies-tests that detect circulating tumor cellular components in the bloodstream-have the potential to transform cancer by reducing health inequities in screening, diagnostics, and monitoring. Today, liquid biopsies are being used to guide treatment choices for patients and monitor for cancer recurrence, and promising work in multi-cancer early detection is ongoing. However, without awareness of the barriers to adoption of this new technology and a willingness to build mitigation efforts into the implementation of widespread liquid biopsy testing, the communities that could most benefit may be the last to access and use them. In this work, we review the challenges likely to affect the accessibility of liquid biopsies in both the general population and underserved populations, and recommend specific actions to facilitate equitable access for all patients.

Background: Hydrofluoric acid (HF) is associated with systemic toxicity, particularly with high-concentration formulations. However, most existing data describe dermal exposures; there is a paucity of data related to outcomes after ingestions., Objective: To determine the morbidity and mortality associated with HF ingestions as reported to the National Poison Data System (NPDS). A secondary objective is to assess for clinical criteria that are associated with serious outcomes after HF ingestion., Methods: We performed a retrospective review of HF ingestions reported to the NPDS from 2007 to 2017. Data including patient demographics, exposure and caller sites, electrolyte abnormalities, treatments, and serious (moderate or major effect or death as documented in NPDS) and non-serious outcomes were abstracted from case narratives. Cases meeting the criteria for a qualifiable HF ingestion were included in the study., Results: During the study period, there were 653 HF ingestions reported to NPDS, of which 142 were included in the final data analysis. Most HF exposures occurred in men (68.3%), and the most common exposure site was at the exposed individual's own residence (78.2%). Nearly half of all exposures (46.5%) were due to transfer into a non-labeled secondary storage container. Total of 45.8% of the cases resulted in a serious outcome. Electrolyte disturbances were associated with an increased risk of a serious outcome. Hypocalcemia was the most frequently reported electrolyte abnormality, occurring in 24.6% of cases. Nine (6.3%) individuals died., Conclusions: Mortality after HF ingestion is low. However, a large cohort of exposures occurred after the transfer of HF to secondary containers. Targeted interventions to reduce this practice are necessary to decrease hazardous chemical exposures., Competing Interests: The authors have no conflicts of interest to report., (© 2023 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Introduction: Medical toxicology is a small but growing specialty. To ensure that the specialty continues to grow and attract strong candidates, it is important to understand what influences physicians to pursue medical toxicology training. This would allow for targeted interventions to recruit strong candidates to the field., Methods: A cross-sectional survey was sent via email to current medical toxicology fellows and to medical toxicologists who completed fellowship in the last 5 years. ACMT listservs were utilized to target recipients. The survey was created through an iterative writing process among the study authors. Responses to the survey were recorded in REDCap. Descriptive statistics were obtained and analyzed., Results: A total of 126 participants responded to the survey request (46 fellows and 80 recent graduates). Most were primarily trained in emergency medicine. Interest in medical toxicology usually started during residency when exposure to the field was highest. Most respondents cite a mentor as a primary influence in pursuing medical toxicology training., Conclusions: Among current fellows and recent graduates of medical toxicology, having a mentor in the field of medical toxicology, having exposure to medical toxicology during residency, and participating in a clinical rotation in medical toxicology were common shared experiences that led to the decision to subspecialize in the field. These results may guide targeted intervention to continue to recruit strong candidates to medical toxicology., (© 2023. American College of Medical Toxicology.)

Significance Statement: We describe circulating proteins associated with albuminuria in a population of African American Study of Kidney Disease and Hypertension with CKD (AASK) using the largest proteomic platform to date: nearly 7000 circulating proteins, representing approximately 2000 new targets. Findings were replicated in a subset of a general population cohort with kidney disease (ARIC) and a population with CKD Chronic Renal Insufficiency Cohort (CRIC). In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in the Black group, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. LMAN2, TNFSFR1B, and members of the ephrin superfamily had the strongest associations. Pathway analysis also demonstrated enrichment of ephrin family proteins., Background: Proteomic techniques have facilitated understanding of pathways that mediate decline in GFR. Albuminuria is a key component of CKD diagnosis, staging, and prognosis but has been less studied than GFR. We sought to investigate circulating proteins associated with higher albuminuria., Methods: We evaluated the cross-sectional associations of the blood proteome with albuminuria and longitudinally with doubling of albuminuria in the African American Study of Kidney Disease and Hypertension (AASK; 38% female; mean GFR 46; median urine protein-to-creatinine ratio 81 mg/g; n =703) and replicated in two external cohorts: a subset of the Atherosclerosis Risk in Communities (ARIC) study with CKD and the Chronic Renal Insufficiency Cohort (CRIC)., Results: In cross-sectional analysis, 104 proteins were significantly associated with albuminuria in AASK, of which 67 of 77 available proteins were replicated in ARIC and 68 of 71 available proteins in CRIC. Proteins with the strongest associations included LMAN2, TNFSFR1B, and members of the ephrin superfamily. Pathway analysis also demonstrated enrichment of ephrin family proteins. Five proteins were significantly associated with worsening albuminuria in AASK, including LMAN2 and EFNA4, which were replicated in ARIC and CRIC., Conclusions: Among individuals with CKD, large-scale proteomic analysis identified known and novel proteins associated with albuminuria and suggested a role for ephrin signaling in albuminuria progression., (Copyright © 2023 by the American Society of Nephrology.)

Background: The objectives of this study were to describe trends in the prevalence of postpartum suicidal behaviors in California, 2013-2018, and to estimate associations between adverse perinatal outcomes and suicidal behaviors. Materials and Methods: We used data from a population-based cohort derived from all birth and fetal death certificates. Records were individually linked to maternal hospital discharge records for the years before and after delivery. We estimated the prevalence of postpartum suicidal ideation and attempt by year. Then, we estimated crude and adjusted associations between adverse perinatal outcomes and these suicidal behaviors. The sample included 2,563,288 records. Results: The prevalence of postpartum suicidal ideation and attempt increased from 2013 to 2018. People with postpartum suicidal behavior were younger, had less education, and were more likely to live in rural areas. A greater proportion of those with postpartum suicidal behavior were Black and publicly insured. Severe maternal morbidity, neonatal intensive care unit admission, and fetal death were associated with greater risk of ideation and attempt. Major structural malformation was not associated with either outcome. Conclusions: The burden of postpartum suicidal behavior has increased over time and is unequally distributed across population subgroups. Adverse perinatal outcomes may help identify individuals that could benefit from additional care during the postpartum period.

Importance: Understanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood., Objective: To determine the association of genetic diseases with infant mortality., Design, Setting, and Participants: This cohort study was conducted at a large pediatric hospital system in San Diego County (California) and included 546 infants (112 infant deaths [20.5%] and 434 infants [79.5%] with acute illness who survived; age, 0 to 1 year) who underwent diagnostic whole-genome sequencing (WGS) between January 2015 and December 2020. Data analysis was conducted between 2015 and 2022., Exposure: Infants underwent WGS either premortem or postmortem with semiautomated phenotyping and diagnostic interpretation., Main Outcomes and Measures: Proportion of infant deaths associated with single-locus genetic diseases., Results: Among 112 infant deaths (54 girls [48.2%]; 8 [7.1%] African American or Black, 1 [0.9%] American Indian or Alaska Native, 8 [7.1%] Asian, 48 [42.9%] Hispanic, 1 [0.9%] Native Hawaiian or Pacific Islander, and 34 [30.4%] White infants) in San Diego County between 2015 and 2020, single-locus genetic diseases were the most common identifiable cause of infant mortality, with 47 genetic diseases identified in 46 infants (41%). Thirty-nine (83%) of these diseases had been previously reported to be associated with childhood mortality. Twenty-eight death certificates (62%) for 45 of the 46 infants did not mention a genetic etiology. Treatments that can improve outcomes were available for 14 (30%) of the genetic diseases. In 5 of 7 infants in whom genetic diseases were identified postmortem, death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission., Conclusions and Relevance: In this cohort study of 112 infant deaths, the association of genetic diseases with infant mortality was higher than previously recognized. Strategies to increase neonatal diagnosis of genetic diseases and immediately implement treatment may decrease infant mortality. Additional study is required to explore the generalizability of these findings and measure reduction in infant mortality.

Scalable technologies to sequence the transcriptomes and epigenomes of single cells are transforming our understanding of cell types and cell states. The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative Cell Census Network (BICCN) is applying these technologies at unprecedented scale to map the cell types in the mammalian brain. In an effort to increase data FAIRness (Findable, Accessible, Interoperable, Reusable), the NIH has established repositories to make data generated by the BICCN and related BRAIN Initiative projects accessible to the broader research community. Here, we describe the Neuroscience Multi-Omic Archive (NeMO Archive; nemoarchive.org), which serves as the primary repository for genomics data from the BRAIN Initiative. Working closely with other BRAIN Initiative researchers, we have organized these data into a continually expanding, curated repository, which contains transcriptomic and epigenomic data from over 50 million brain cells, including single-cell genomic data from all of the major regions of the adult and prenatal human and mouse brains, as well as substantial single-cell genomic data from non-human primates. We make available several tools for accessing these data, including a searchable web portal, a cloud-computing interface for large-scale data processing (implemented on Terra, terra.bio), and a visualization and analysis platform, NeMO Analytics (nemoanalytics.org)., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: Many studies of sudden unexpected infant death (SUID) have focused on individual domains of risk factors (maternal, infant, and environmental), resulting in limited capture of this multifactorial outcome. The objective of this study was to examine the geographic distribution of SUID in San Diego County, and assess maternal, infant, and environmental risk factors from a large, administrative research platform., Study Design: Births in California between 2005 and 2017 were linked to hospital discharge summaries and death files. From this retrospective birth cohort, cases of SUID were identified from infant death files in San Diego County. We estimated adjusted hazard ratios (aHRs) for infant, maternal, and environmental factors and SUID in multivariable Cox regression analysis. Models were adjusted for maternal sociodemographic characteristics and prenatal nicotine exposure., Results: There were 211 (44/100,000 live births; absolute risk 0.04%) infants with a SUID among 484,905 live births. There was heterogeneity in geographic distribution of cases. Multiparity (0.05%; aHR 1.4, 95% confidence interval (CI) 1.1, 1.9), maternal depression (0.11%; aHR 1.8, 95% CI 1.0, 3.4), substance-related diagnoses (0.27%; aHR 2.3, 95% CI 1.3, 3.8), cannabis-related diagnosis (0.35%; aHR 2.7, 95% CI 1.5, 5.0), prenatal nicotine use (0.23%; aHR 2.5, 95% CI 1.5, 4.2), preexisting hypertension (0.11%; aHR 2.3, 95% CI 1.2, 4.3), preterm delivery (0.09%; aHR 2.1, 95% CI 1.5, 3.0), infant with a major malformation (0.09%; aHR 2.0, 95% CI 1.1, 3.6), respiratory distress syndrome (0.12%; aHR 2.6, 95% CI 1.5, 4.6), and select environmental factors were all associated with SUID., Conclusions: Multiple risk factors were confirmed and expanded upon, and the geographic distribution for SUID in San Diego County was identified. Through this approach, prevention efforts can be targeted to geographies that would benefit the most.

Objective: The objective was to investigate maternal and pregnancy characteristics associated with neonatal encephalopathy (NE)., Study Design: We queried an administrative birth cohort from California between 2011 and 2017 to determine the association between each factor and NE with and without hypothermia treatment., Results: From 3 million infants born at 35 or more weeks of gestation, 6,857 cases of NE were identified (2.3 per 1000 births), 888 (13%) received therapeutic hypothermia. Risk factors for NE were stronger among cases receiving hypothermia therapy. Substance-related diagnosis, preexisting diabetes, preeclampsia, and any maternal infection were associated with a two-fold increase in risk. Maternal overweight/obesity, nulliparity, advanced maternal age, depression, gestational diabetes or hypertension, and short or long gestations also predicted NE. Young maternal age, Asian race and Hispanic ethnicity, and cannabis-related diagnosis lowered risk of NE., Conclusions: By disseminating these results, we encourage further interrogation of these perinatal factors., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Accidental consumption of poisonous mushrooms can result in serious illness and death (1). Reports of severe poisonings from consumption of foraged mushrooms for food or hallucinogenic purposes increased during 1999-2016 (2), and approximately 7,500 poisonous mushroom ingestions were reported annually to poison control centers across the United States (1). To estimate the frequency of emergency department (ED) visits, hospitalizations, and severe adverse outcomes associated with accidental poisonous mushroom ingestion in the United States, CDC analyzed 2016 data from the Healthcare Cost and Utilization Project's* Nationwide Emergency Department Sample (HCUP-NEDS) and National Inpatient Sample (HCUP-NIS) databases as well as 2016-2018 data from three IBM MarketScan sources: Commercial Claims and Encounters (CCAE), Medicare Supplemental and Coordination of Benefits (Medicare), and Multi-State Medicaid databases. During 2016, 1,328 (standard error [SE] = 100) ED visits and 100 (SE = 22) hospitalizations (HCUP data) were associated with accidental poisonous mushroom ingestion. Among 556 patients with a diagnosis of accidental poisonous mushroom ingestion, 48 (8.6%) patients experienced a serious adverse outcome during 2016-2018 (MarketScan data). Serious adverse outcomes were more common among Medicaid-insured patients than among patients with commercial insurance or Medicare (11.5% versus 6.7%, p = 0.049). Because most mushroom poisonings are preventable, wild mushrooms should not be consumed unless they are identified by an expert; increased public health messaging about the potential dangers of mushroom poisoning is needed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objective: Rituximab is a CD20-directed cytolytic antibody used for non-Hodgkin lymphoma, chronic lymphocytic leukaemia and RA, and off label for JIA, multiple sclerosis and lupus. Owing to concerns about infant B cell depletion, the manufacturer recommends avoidance of rituximab throughout pregnancy and for 12 months before conception. The aim of this study was to add to the limited data on pregnancy outcomes in women with exposure to rituximab., Methods: Data were obtained from MotherToBaby Pregnancy Studies. Participants were enrolled prospectively into this observational study between 2007 and 2019. Pregnancy exposure and outcome data were collected from medical records, telephone interviews and dysmorphology examinations. The outcomes examined included spontaneous abortion, stillbirth, premature delivery, pregnancy complications, major and minor anomalies, small for gestational age, neonatal complications and serious infections., Results: We classified 19 women with exposure to rituximab into three groups. Group A included three women who received rituximab during pregnancy. Group B included three women who received their last infusion before conception but had assumed pregnancy exposure owing to the long half-life of the drug. Group C included 13 women who used rituximab in the 2 years before pregnancy, with the last infusion given no sooner than five half-lives before conception. Three children had a major structural defect. Preterm delivery occurred in two pregnancies, and two infants were small for gestational age on birth weight. No cases of B cell depletion were reported., Conclusion: No pattern of major structural anomalies or other adverse outcomes was reported in this case series., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Cyanide (CN) toxicity commonly occurs during enclosed-space fires. Historically, the first step in treating CN toxicity utilized amyl nitrite and sodium nitrite to induce methemoglobinemia, which can be dangerous in this population. Hydroxocobalamin (OHCob), which binds to CN to form the nontoxic metabolite cyanocobalamin, is now the first-line antidote for CN toxicity, and has the advantage of not inducing methemoglobinemia., Case Report: A 62-year-old man presented to the Emergency Department (ED) after a house fire. He was intubated for respiratory distress and hypoxia with an initial carboxyhemoglobin of 1.3%, methemoglobin 0.3%, and anion gap 19. Eleven hours after presentation, his serum lactic acid was 9 mmol/L. Given his continued deterioration, 14 h after arrival he received OHCob 5 g i.v. for presumed CN toxicity. Methemoglobin concentration 4 min prior to OHCob administration was 0.7%, and 2 h after administration was 4.2%. This subsequently increased to 14.3% (16 h after OHCob administration) and peaked at 16.3% (47 h after OHCob administration), at which time he was administered a dose of methylene blue 50 mg i.v., 60 h after ED arrival. His methemoglobin concentrations fluctuated until a consistent downward trend starting at 92 h from ED arrival. He continued to deteriorate and expired on hospital day 5 with a methemoglobin concentration of approximately 6.0%. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: CN toxicity requires immediate recognition and treatment. The antidote, OHCob, is believed to not induce methemoglobinemia. However, this potential side effect must be considered by emergency physicians when treating suspected CN toxicity, especially if the patient does not improve after antidotal therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: To date, limited information is available on the characteristics of adolescents with e-cigarette, or vaping, product use-associated lung injury (EVALI)., Objective: To inform public health and clinical practice by describing differences in demographics, substance use behaviors, and clinical characteristics of EVALI among adolescents compared with adults., Design, Setting, and Participants: Surveillance data reported to the Centers for Disease Control and Prevention during the 2019 EVALI outbreak were used to calculate adjusted prevalence ratios (aPRs) with 95% CIs and to test differences between 360 hospitalized or deceased adolescents vs 859 young adults and 936 adults with EVALI (N = 2155)., Main Outcomes and Measures: Demographics, substance use behaviors, and clinical characteristics., Results: Included in this cross-sectional study were 360 hospitalized or deceased adolescents (age range, 13-17 years; 67.9% male) vs 859 young adults (age range, 18-24 years; 72.4% male) and 936 adults (age range, 25-49 years; 65.6% male) with EVALI. Adolescents diagnosed as having EVALI reported using any nicotine-containing (62.4%), any tetrahydrocannabinol (THC)-containing (81.7%), and both (50.8%) types of e-cigarette or vaping products. Informal sources for obtaining nicotine-containing and THC-containing e-cigarette or vaping products were more commonly reported by adolescents (50.5% for nicotine and 96.5% for THC) than young adults (19.8% for nicotine [aPR, 2.49; 95% CI, 1.78-3.46] and 86.9% for THC [aPR, 1.11; 95% CI, 1.05-1.18]) or adults (24.3% for nicotine [aPR, 2.06; 95% CI, 1.49-2.84] and 75.1% for THC [aPR, 1.29; 95% CI, 1.19-1.40]). Mental, emotional, or behavioral disorders were commonly reported; a history of attention-deficit/hyperactivity disorder was almost 4 times more likely among adolescents (18.1%) than adults (4.9%) (aPR, 3.74; 95% CI, 1.92-7.26). A history of asthma was more likely to be reported among adolescents (43.6%) than adults (28.3%) (aPR, 1.53; 95% CI, 1.14-2.05). Gastrointestinal and constitutional symptoms were more common in adolescents (90.9% and 97.3%, respectively) than adults (75.3% and 94.5%, respectively) (aPR, 1.20; 95% CI, 1.13-1.28 and aPR, 1.03; 95% CI, 1.00-1.06, respectively). Because of missing data, percentages may not be able to be calculated from data provided., Conclusions and Relevance: Public health and clinical professionals should continue to provide information to adolescents about the association between EVALI and THC-containing e-cigarette or vaping product use, especially those products obtained through informal sources, and that the use of any e-cigarette or vaping product is unsafe. Compared with adults, it appears that adolescents with EVALI more frequently have a history of asthma and mental, emotional, or behavioral disorders, such as attention-deficit/hyperactivity disorder, and report nonspecific problems, including gastrointestinal and constitutional symptoms; therefore, obtaining a confidential substance use history that includes e-cigarette or vaping product use is recommended.

Three siblings with inhalational elemental mercury toxicity presented with fever, rash, and upper respiratory tract symptoms. The patients were heavily exposed to elemental mercury that was spilled in their home and then vacuumed. Initial whole blood mercury levels were elevated at >200 µg/L, 153 µg/L and 130 µg/L (Mayo Clinic Laboratories lab reference range <9 µg/L) for Cases 1, 2, and 3, respectively. All three required chelation with succimer. Clinically significant elemental mercury toxicity can resemble an infectious illness. Severe morbidity and mortality can be prevented if heavy metal poisoning is considered early, through a detailed history including an environmental exposure history. For elemental mercury spills in the home, safe and effective clean-up steps are needed. Improved public health education is needed to prevent similar household exposures., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No conflicts of interest were disclosed. All members of the Lung Injury Response Clinical Working Group have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Carolyn S. Calfee reports a grant from the FDA/NIH (Tobacco Center of Regulatory Science [TCORS]) for a project entitled Impact of Different E-cigarette Characteristics on Acute Lung Injury; a grant from GlaxoSmithKline for an observational study on sepsis and ARDS biomarkers; a grant and personal fees from Bayer for an observational study on pulmonary hypertension in ARDS and for medical consultation; and personal fees from Roche/Genentech for consultation on potential therapies for ARDS, and personal fees from Prometic, CSL Behring, and Quark for serving on medical advisory boards for ARDS. No other potential conflicts of interest were disclosed.

Objective: Atherosclerotic cardiovascular disease (ASCVD) is an increasing cause of morbidity and mortality in people with HIV since the introduction of combination antiretroviral therapy. Despite recent advances in our understanding of HIV ASCVD, controversy still exists on whether this increased risk of ASCVD is due to chronic HIV infection or other risk factors. Mounting biomarker studies indicate a role of monocyte/macrophage activation in HIV ASCVD; however, little is known about the mechanisms through which HIV infection mediates monocyte/macrophage activation in such a way as to engender accelerated atherogenesis. Here, we experimentally investigated whether HIV expression is sufficient to accelerate atherosclerosis and evaluated the role of caspase-1 activation in monocytes/macrophages in HIV ASCVD. Approach and Results: We crossed a well-characterized HIV mouse model, Tg26 mice, which transgenically expresses HIV-1, with ApoE -/- mice to promote atherogenic conditions (Tg26 +/- /ApoE -/- ). Tg26 +/- /ApoE -/- have accelerated atherosclerosis with increased caspase-1 pathway activation in inflammatory monocytes and atherosclerotic vasculature compared with ApoE -/- . Using a well-characterized cohort of people with HIV and tissue-banked aortic plaques, we documented that serum IL (interleukin)-18 was higher in people with HIV compared with non-HIV-infected controls, and in patients with plaques, IL-18 levels correlated with monocyte/macrophage activation markers and noncalcified inflammatory plaques. In autopsy-derived aortic plaques, caspase-1+ cells and CD (clusters of differentiation) 163+ macrophages correlated., Conclusions: These data demonstrate that expression of HIV is sufficient to accelerate atherogenesis. Further, it highlights the importance of caspase-1 and monocyte/macrophage activation in HIV atherogenesis and the potential of Tg26 +/- /ApoE -/- as a tool for mechanistic studies of HIV ASCVD.

Many conditions that require frequent medication use are common during pregnancy. The purpose of this article is to list some of the most common of these disorders and to discuss the risk to the developing fetus of the medications used most frequently to treat them. Included are drugs used for the treatment of asthma, nausea and vomiting, hyperthyroidism, pain and fever, and depression during pregnancy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

For the last 30 years, pregnancy exposure studies, with varying methodologies, have been the mainstay of post-marketing surveillance for new drugs likely to be used by women of reproductive age. While they provide valuable data to inform use during pregnancy, they have limitations that render them necessary but not sufficient in supplying timely information to patients and prescribers. The Organization of Teratology Information Specialists MotherToBaby Pregnancy Studies' collaborative research group operates to help fill this gap. This paper provides an overview of the research that has been and is currently being conducted, as well as best practices determined over the past two decades. The Organization of Teratology Information Specialists MotherToBaby studies can provide earlier signaling with regard to concerns following possible teratogenic exposures, which when examined in conjunction with larger database studies and case-control designs, can move us closer to developing a fuller picture of drug safety for women of reproductive age.

Objective: To survey an international sample of providers to determine their current practices for the prevention, screening, and treatment of congenital heart block (CHB) due to maternal Ro/SSA antibodies., Methods: A survey was designed by the organizing committee of the 9th International Conference of Reproduction, Pregnancy and Rheumatic Diseases. It was sent to attendants of the conference and authors of recent publications or abstracts at ACR 2012, 2013 or 2014 on rheumatic diseases and pregnancy., Results: In anti-Ro/SSA positive women, 80% of 49 respondents recommended screening by serial fetal echocardiogram (ECHO), with most starting at week 16 (59%) and stopping at week 28 (25%), although the time to stop varied widely. For women without a prior infant with neonatal lupus, respondents recommend every other week (44%) or weekly (28%) fetal ECHOs. For women with a prior infant with neonatal lupus, 80% recommend weekly fetal ECHOs. To prevent CHB, HCQ was recommended by 67% of respondents and most would start pre-pregnancy (62%). Respondents were asked about medications to treat varying degrees of CHB in a 20-week pregnant, anti-Ro and La positive SLE patient. For first degree, respondents recommended starting dexamethasone (53%) or HCQ (43%). For second degree, respondents recommended starting dexamethasone (88%). For third degree, respondents recommended starting dexamethasone (55%) or IVIg (33%), although 27% would not start treatment., Conclusion: Despite the absence of official guidelines, many physicians with a focus on pregnancy and rheumatic disease have developed similar patterns in the screening, prevention and treatment of CHB.

Purpose: Advances in health-related quality-of-life (HRQL) measurement enable point-of-care assessments. We incorporated the Patient-Reported Outcomes Measurement Information System (PROMIS ® ) Global Health Scale in routine outpatient evaluations of adolescent and young adult (AYA) oncology patients and survivors at two geographically distinct U.S. institutions., Methods: AYAs (18-39 years old) completed the 10-question PROMIS Global. Summary subscale scores for Global Physical Health (GPH) and Global Mental Health (GMH) were produced using established scoring algorithms (standardized mean = 50, standard deviation = 10). In addition to comparisons by treatment status, associations between lower subscale scores (<45, previously defined as clinically meaningful) and patient characteristics were assessed using two-sample t-tests among those off treatment., Results: Of 147 patients approached, 142 consented. Mean age was 24.6 ± 5.3 years; 53.5% were male; and 61.3% had hematologic malignancies. Most (76%) were off treatment; 43.0% had treatment complications. While mean GPH and GMH scores did not differ from the standardized population mean (GPH, 49.7 ± 8.8, p = 0.73; GMH, 50.5 ± 9.3, p = 0.55), mean GPH scores were lower among those on treatment (44.3 ± 9.0) than off treatment (51.5 ± 8.1, p < 0.0001). There was no difference in GMH scores by treatment status. Among those off treatment, 26.9% of GPH and 22.2% of GMH scores were <45. The only factor associated with lower GPH scores was treatment complications; no factors were associated with lower GMH scores., Conclusion: Point-of-care HRQL assessment with AYAs is feasible. Among patients off treatment, GPH scores were lower for patients with treatment complications. Further research is needed to understand factors associated with lower GMH scores in this AYA oncology population.

Purpose: The adolescent and young adult (AYA) population is a growing group of survivors, exceeding more than 600,000, at high risk for late effects of cancer-directed therapy. While many guidelines exist for cancer survivorship care, choosing which to use for an AYA cancer survivor is challenging, yet vital, to ensure comprehensive follow-up care., Methods: Survivorship care plans (SCPs), including treatment summaries (TS) and follow-up care plans, were created for three clinical vignettes (acute lymphoblastic leukemia, osteosarcoma, and Hodgkin lymphoma). Four sets of guidelines were used, including the Children's Oncology Group Long-Term Follow-Up Guidelines (COG LTFU), National Comprehensive Cancer Network (NCCN) Guidelines for Age- Related Recommendations: AYA Oncology (NCCN-AYA), NCCN Guidelines for Treatment of Cancer by Site (NCCN-Site), and NCCN Guidelines for Supportive Care: Survivorship (NCCN-Survivorship) and NCCN supplemental cancer screening guidelines. The follow-up care plans were compared across guidelines to determine the extent and nature of the similarities and differences concerning AYA cancer survivorship care., Results: The guidelines disagree on the link between treatment exposures and late effects, the population to be screened, the screening test to be used, and the time interval of testing. Specific examples of this include screening for cardiac toxicity, breast cancer, and neurocognitive deficits., Conclusions: While many guidelines exist for AYA survivorship care, there is discordance among the recommendations. This has significant implications for the long-term follow-up care of an AYA survivor. This study offers solutions to harmonize guidelines in order to ensure comprehensive quality survivorship care for this population.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.)

Bacterial cold water disease (BCWD) is a chronic disease of rainbow trout, and is caused by the Gram-negative bacterium Flavobacterium psychrophilum (Fp), a common aquaculture pathogen. The National Center for Cool and Cold Water Aquaculture has bred two genetic lines of rainbow trout: a line of Fp-resistant trout (ARS-Fp-R or R-line trout) and a line of susceptible trout (ARS-Fp-S, or S-line). Little is known about how phenotypic selection alters immune response parameters or how such changes relate to genetic disease resistance. Herein, we quantify interindividual variation in the distribution and abundance of B cell populations (B cell signatures) and examine differences between genetic lines of naive animals. There are limited trout-specific cell surface markers currently available to resolve B cell subpopulations and thus we developed an alternative approach based on detection of differentially expressed transcription factors and intracellular cytokines. B cell signatures were compared between R-line and S-line trout by flow cytometry using antibodies against transcription factors early B cell factor-1 (EBF1) and paired domain box protein Pax5, the pro-inflammatory cytokine IL-1β, and the immunoglobulin heavy chain mu. R-line trout had higher percentages of EBF(+) B myeloid/ progenitor and pre-B cells in PBL, anterior and posterior kidney tissues compared to S-line trout. The opposite pattern was detected in more mature B cell populations: R-line trout had lower percentages of both IgM(+) mature B cells and IgM-secreting cells in anterior kidney and PBL compared to S-line trout. In vitro LPS-activation studies of PBL and spleen cell cultures revealed no significant induction differences between R-line and S-line trout. Together, our findings suggest that selective resistance to BCWD may be associated with shifts in naive animal developmental lineage commitment that result in decreased B lymphopoiesis and increased myelopoiesis in BCWD resistant trout relative to susceptible trout., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Recent studies suggest that the anti-diabetic drug metformin may reduce the risk of cancer and have anti-proliferative effects for some but not all cancers. In this study, we examined the effects of metformin on human retinoblastoma cell proliferation in vitro and in vivo. Two different human retinoblastoma cell lines (Y79, WERI) were treated with metformin in vitro and xenografts of Y79 cells were established in nu/nu immune-deficient mice and used to assess the effects of pharmacological levels of metformin in vivo. Metformin inhibited proliferation of the retinoblastoma cells in vitro. Similar to other studies, high concentrations of metformin (mM) blocked the cell cycle in G0‑G1, indicated by a strong decrease of G1 cyclins, especially cyclin D, cyclin-dependent kinases (4 and 6), and flow cytometry assessment of the cell cycle. This was associated with activation of AMPK, inhibition of the mTOR pathways and autophagy marker LC3B. However, metformin failed to suppress growth of xenografted tumors of Y79 human retinoblastoma cells in nu/nu mice, even when treated with a maximally tolerated dose level achieved in human patients. In conclusion, suprapharmacological levels (mM) of metformin, well above those tolerated in vivo, inhibited the proliferation of retinoblastoma cells in vitro. However, physiological levels of metformin, such as seen in the clinical setting, did not affect the growth of retinoblastoma cells in vitro or in vivo. This suggests that the potential beneficial effects of metformin seen in epidemiological studies may be limited to specific tumor types or be related to indirect effects/mechanisms not observed under acute laboratory conditions.

Several studies in recent years have described protocols, both genetic- and culture-based, that induce the differentiation of embryonic stem (ES) cells towards a pancreatic beta-cell type. The success of previous protocols in generating insulin-producing beta-cells has been questioned due in part to uncertainty regarding cell lineage but also due to the controversy regarding the source of any insulin detected in these cells. In an attempt to address the latter, we designed a novel assay that can identify de novo insulin synthesis. The method is based on metabolic labeling combined with a modified radio-immunoassay and will routinely detect less than 5 pg/microl of de novo insulin synthesis in lysates from the insulinoma cell line MIN6. This assay failed to detect any newly translated insulin in an ES cell-derived population generated using an adapted version of a previously published, 5-stage differentiation protocol. In combination with other techniques, including immunofluorescent staining and western blot analysis to detect and quantify C-peptide, we conclude that the majority of the insulin found in these differentiated ES cell cultures is medium-derived.