A graded neonatal mouse model of necrotizing enterocolitis demonstrates that mild enterocolitis is sufficient to activate microglia and increase cerebral cytokine expression.

Background: Necrotizing enterocolitis (NEC) is an inflammatory gastrointestinal process that afflicts approximately 10% of preterm infants born in the United States each year, with a mortality rate of 30%. NEC severity is graded using Bell's classification system, from stage I mild NEC to stage III severe NEC. Over half of NEC survivors present with neurodevelopmental impairment during adolescence, a long-term complication that is poorly understood but can occur even after mild NEC. Although multiple animal models exist, none allow the experimenter to control nor represent the gradient of symptom severities seen in NEC patients. We bridge this knowledge gap by developing a graded murine model of NEC and studying its relationship with neuroinflammation across a range of NEC severities. Methods: Postnatal day 3 (P3) C57BL/6 mice were fed a formula containing different concentrations (0% control, 0.25%, 1%, 2%, and 3%) of dextran sodium sulfate (DSS). P3 mice were fed every 3 hours for 72-hours. We collected data on weight gain and behavior (activity, response, body color) during feeding. At the end of the experiment, we collected tissues (intestine, liver, plasma, brain) for immunohistochemistry, immunofluorescence, and cytokine and chemokine analysis. Results: Throughout NEC induction, mice fed higher concentrations of DSS died sooner, lost weight faster, and became sick or lethargic earlier. Intestinal characteristics (dilation, color, friability) were worse in mice fed with higher DSS concentrations. Histology revealed small intestinal disarray among mice fed all DSS concentrations, while higher DSS concentrations resulted in reduced small intestinal cellular proliferation and increased hepatic and systemic inflammation. In the brain, IL-2, G-CSF, and CXCL1 concentrations increased with higher DSS concentrations. Although the number of neurons and microglia in the CA1 hippocampal region did not differ, microglial branching was significantly reduced in DSS-fed mice. Conclusion: We characterize a novel graded model of NEC that recapitulates the full range of NEC severities. We show that mild NEC is sufficient to initiate neuroinflammation and microglia activation. This model will facilitate studies on the neurodevelopmental effects of NEC.

Associations of a toenail metal mixture with attention and memory in the Gulf long-term follow-up (GuLF) study.

BACKGROUND: Research on metal-associated neurodegeneration has largely focused on single metals. Since metal exposures typically co-occur as combinations of both toxic and essential elements, a mixtures framework is important for identifying risk and protective factors. This study examined associations between toenail levels of an eight-metal mixture and attention and memory in men living in US Gulf states. METHODS: We measured toenail concentrations of toxic (arsenic, chromium, lead, and mercury) and essential (copper, manganese, selenium, and zinc) metals in 413 non-smoking men (23-69 years, 46 % Black) from the Gulf Long-Term Follow-Up (GuLF) Study. Sustained attention and working memory were assessed at the time of toenail sample collection using the continuous performance test (CPT) and digit span test (DST), respectively. Associations between toenail metal concentrations and performance on neurobehavioral tests were characterized using co-pollutant adjusted general linear models and Bayesian Kernel Machine Regression. RESULTS: Adjusting for other metals, one interquartile range (IQR) increase in toenail chromium was associated with a 0.19 (95 % CI: -0.31, -0.07) point reduction in CPT D Prime score (poorer ability to discriminate test signals from noise). One IQR increase in toenail manganese was associated with a 0.20 (95 % CI, -0.41, 0.01) point reduction on the DST Reverse Count (fewer numbers recalled). Attention deficits were greater among Black participants compared to White participants for the same increase in toenail chromium concentrations. No evidence of synergistic interaction between metals or adverse effect of the overall metal mixture was observed for either outcome. CONCLUSIONS: Our findings support existing studies of manganese-related memory deficits and are some of the first to show chromium related attention deficits in adults. Longitudinal study of cognitive decline is needed to verify chromium findings. Research into social and chemical co-exposures is also needed to explain racial differences in metal-associated neurobehavioral deficits observed in this study.

Nunchaku-like Free Fibula Osteocutaneous Flap in Through-and-through Composite Oromandibular Defect Reconstruction.

The free fibula osteocutaneous flap (FFOCF) has been used for oromandibular reconstruction over several decades. However, when facing through-and-through composite oromandibular defects (COMDs), significant challenges still arise. The complexity of COMD necessitates the reconstruction of bone, intraoral mucosa, and extraoral skin. Additional flaps are often needed, which extend surgical durations and heighten associated risks. This report presents a 62-year-old man with squamous cell carcinoma of the left lower gingiva. After ablative surgery, successful reconstruction of a through-and-through COMD was achieved with a single FFOCF through innovative design. The flap was osteotomized into 2 segments with attached skin islands while preserving the vascular pedicle. Rotation of 1 segment created 2 skin islands on opposing sides, simultaneously repairing intraoral and extraoral defects. Postoperative outcomes at the 1-month follow-up were encouraging. Although technically challenging, the "Nunchaku-like FFOCF" offers a safe and effective approach for the comprehensive reconstruction of through-and-through COMD.

Pitch Variation Skills in Cantonese Speakers With Apraxia of Speech After Stroke: Preliminary Findings of Acoustic Analyses.

PURPOSE: Literature on apraxia of speech (AOS) in Chinese speakers is sparse compared to the English literature. This study aims to examine the pitch variation skills of Cantonese adults with AOS poststroke in terms of perceptual tone accuracy, acoustic fundamental frequency (fo) changes, and repetition durations on items with different syllable structures, lexical status, and tone syllables in various positions in a sequencing context. METHOD: Six Cantonese adults with AOS poststroke (AOS group), six adults without AOS poststroke (nAOS group), and six healthy controls (HC group) performed the tone sequencing task (TST), which was adapted from oral diadochokinetic tasks, with three different tone syllables. Tone accuracy, fo values across 10 time points, and acoustic repetition durations were compared within and between the groups. RESULTS: The AOS group produced significantly lower tone accuracy and different fo changes on the three Cantonese tone syllables compared with the control groups and significantly longer repetition durations than the HC group. The AOS group showed more difficulty with the tone syllables with the consonant-vowel structure, while a priming effect was observed on the T2 (high-rising) syllables with lexical meanings. A unique lowering of fo in the final syllable of the trisyllabic items was observed only in the AOS group. CONCLUSIONS: The AOS group showed degraded pitch variation skills. The effects of the three linguistic elements were discussed. Future investigations are called for to adapt the TST in other tonal languages to determine if degraded pitch variation skills are present in other tonal language speakers with AOS.

Metal Concentrations in E-Cigarette Aerosol Samples: A Comparison by Device Type and Flavor.

BACKGROUND: The rapid evolution of electronic cigarette (e-cigarette) products warrants surveillance of the differences in exposure across device types-modifiable devices (MODs), cartridge ("pod")-containing devices (PODs), disposable PODs (d-PODs)-and flavors of the products available on the market. OBJECTIVE: This study aimed to measure and compare metal aerosol concentrations by device type and common flavors. METHODS: We collected aerosol from 104 MODs, 67 PODs (four brands: JUUL, Bo, Suorin, PHIX), and 23 d-PODs (three brands: ZPOD, Bidi, Stig) via droplet deposition in a series of conical pipette tips. Metals and metalloids [aluminum (Al), arsenic (As), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), antimony (Sb), tin (Sn), and zinc (Zn)] were measured using inductively coupled plasma mass spectrometry (ICP-MS), results were log-transformed for statistical analysis, and concentrations are reported in aerosol units (mg/m3). RESULTS: Of the 12 elements analyzed, concentrations were statistically significantly higher in MOD devices, except for Co and Ni, which were higher in PODs and d-PODs. Of the POD brands analyzed, PHIX had the highest median concentrations among four metals (Al, Ni, Pb, and Sn) compared to the rest of the POD brands. According to POD flavor, seven metals were three to seven orders of magnitude higher in tobacco-flavored aerosol compared to those in mint and mango flavors. Among the d-POD brands, concentrations of four metals (Al, Cu, Ni, and Pb) were higher in the ZPOD brand than in Bidi Stick and Stig devices. According to d-POD flavor, only Cr concentrations were found to be statistically significantly higher in mint than tobacco-flavored d-PODs. DISCUSSION: We observed wide variability in aerosol metal concentrations within and between the different e-cigarette device types, brands, and flavors. Overall, MOD devices generated aerosols with higher metal concentrations than PODs and d-PODs, and tobacco-flavored aerosols contained the highest metal concentrations. Continued research is needed to evaluate additional factors (i.e., nicotine type) that contribute to metal exposure from new and emerging e-cigarette devices in order to inform policy. https://doi.org/10.1289/EHP11921.

Characterization of e-cigarette users according to device type, use behaviors, and self-reported health outcomes: Findings from the EMIT study.

INTRODUCTION: Electronic cigarettes (e-cigarettes) rapidly evolved from large modifiable (MOD) devices, to small and affordable 'POD' devices. Detailed information on user demographics and preferences according to device type, which can inform potential chemical exposure and policy recommendations, is currently limited. The goal of this study is to describe user demographics, use behaviors and preferences, as well as self-reported health outcomes according to the e-cigarette device type used. METHODS: From April 2019 to March 2020, 91 participants from Maryland (18 MOD users, 26 POD users, 16 dual users (use of both combustible and e-cigarettes), and 31 non-users (never e-cigarette users and never smokers or >6 months former use) were recruited. A comprehensive questionnaire collected sociodemographic characteristics, e-cigarette/tobacco use behaviors, self-reported health outcomes, device characteristics and preferences. Chi-squared tests for categorical variables, ANOVA for continuous variables, qualitative thematic analysis, linear and logistic regressions were used to assess relationships between variables and groups. RESULTS: POD users were younger (average 22.5 years) than MOD users (30.8 years) or dual users (34.3 years) (p<0.001). MOD users reported more puffs per day (mean ± SD: 373 ± 125 puffs) compared to POD users (123.0 ± 172.5). E-cigarette users who were former smokers used 1.16 mg/mL lower nicotine concentrations compared to lifetime exclusive e-cigarette users (p=0.03) in linear models. Exclusive POD users self-reported more coughing than exclusive MOD or dual users (p=0.02). E-cigarette users reported more shortness of breath, headaches, and fatigue from their e-cigarette use compared to non-users. CONCLUSIONS: We found significant differences between user demographics, e-cigarette preferences, device characteristics, and use behaviors by user group. This information can help explain exposure to chemicals from e-cigarettes, including compounds with known toxic effects (e.g. metals, formaldehyde), and help inform the design of prevention and intervention strategies and policy decisions.

Residential proximity to metal emitting industries and toenail metal concentration in the US Gulf States.

Objective: The US Gulf region is heavily reliant on metal-emitting petrochemical and manufacturing industries. We characterized the effect of residential proximity to metal-emitting sites and metal body burden in Gulf states residents with particular attention to potential differential exposure burden by race. Methods: We measured toenail concentrations of arsenic, chromium, lead, manganese, mercury, and selenium using inductively coupled plasma mass spectrometry in 413 non-smoking men from the Gulf Long-term Follow-Up Study. Point sources of industrial metal emissions were identified using the US EPA's National Emissions Inventory (NEI) database and geocoded to participant residential addresses. For each metal, we assessed associations of toenail metal concentrations with the inverse-distance weighted number of emissions sites and volume of air-metal emissions within 30 km radial buffers of participant residences using multivariable linear regression. Results were stratified by race. Results: Compared to self-identified Non-Hispanic (NH) White participants, NH Black participants lived closer to NEI sites but had 23-70% lower toenail metal concentrations adjusting for other personal/behavioral factors. Residential proximity to lead-emitting NEI sites was positively associated with toenail Pb concentration while proximity to mercury-emitting NEI sites was inversely associated with toenail Hg concentration. Findings for lead were significantly attenuated after adjustment for neighborhood-level socioeconomic factors. Conclusion: Residential proximity to lead-emitting NEI sites in the US Gulf region is associated with a higher body burden of lead. However, this relationship may be driven in part by non-NEI factors related to residence in industry-adjacent neighborhoods.

Development of a gastrocutaneous fistula from a marginal ulcer after repair of duodenal injury with pyloric exclusion.

Introduction: Duodenal trauma is rare but can be associated with significant morbidity and mortality (Pandey et al., 2011). Adjunct procedures, such as pyloric exclusion, can be performed to assist in surgical repair of these injuries. However, pyloric exclusion can lead to severe long-term complications associated with significant morbidity that can be difficult to repair. Case: A 35-year-old man with a history of duodenal trauma from a gunshot wound (GSW) status post pyloric exclusion and Roux-en-Y gastrojejunostomy presented to the Emergency Department (ED) with complaints of abdominal pain and leakage of food particles and fluid from an open wound around his surgical scar. Computed tomography (CT) scan on admission showed a tract extending from the gastrojejunostomy anastomosis to the skin representing a fistula. Esophago-gastro-duodenoscopy (EGD) reconfirmed a large marginal ulcer that had fistulized to the skin. After nutritional repletion, the patient was taken to the operating room (OR) for takedown of the enterocutaneous fistula and Roux-en-Y gastrojejunostomy, closure of gastrostomy and enterotomy, pyloroplasty and feeding jejunostomy tube placement. The patient was re-admitted after discharge with abdominal pain, vomiting and early satiety. EGD showed gastric outlet obstruction and severe pyloric stenosis which was managed with endoscopic balloon dilation. Conclusion: This case represents the severe and potentially life-threatening complications that may occur after pyloric exclusion with Roux-en-Y gastrojejunostomy. Gastrojejunostomies are prone to marginal ulceration which can perforate if not adequately treated. Free perforations cause peritonitis, but if the perforation is contained it can erode through the abdominal wall creating the rare complication of a gastrocutaneous fistula. Even after restoration of normal anatomy with a pyloroplasty, patients may suffer additional complications such as pyloric stenosis requiring continued intervention.

Reliability of low mass toenail samples as biomarkers of chronic metal exposure.

BACKGROUND: Toenails are a promising matrix for chronic metal exposure assessment, but there are currently no standard methods for collection and analysis. Questions remain about sample mass requirements and the extent to which metals measured in this matrix are representative of chronic body burden. OBJECTIVE: This study proposes a method to maximize sample conservation for toenail metals analysis using inductively coupled plasma mass spectrometry (ICP-MS). We demonstrate the reliability of an ~25 mg toenail sample (typically 1-2 clippings) for metals analysis and evaluate the intra-individual variability of multiple metals in this matrix over time in men from the Gulf Long-term Follow-up (GuLF) Study. METHODS: Toenail samples from 123 GuLF Study participants were collected at two visits 3 years apart and analyzed for 18 elements using ICP-MS. Participants with samples exceeding 200 mg at the first visit (n = 29) were selected for triplicate sub-sample analysis. Kendall's coefficient of concordance (W) was used to assess sub-sample reliability and Spearman's correlation coefficients (ρ) were used to evaluate fluctuations in elemental concentrations over time. RESULTS: Results were not reported for Cd, Co, Mo, Sb, and V (detected in <60% of the samples). There was strong agreement among triplicate samples (Kendall's W: 0.72 (Cu)-0.90 (Cu)) across all elements evaluated, moderate correlations of elemental concentrations (Spearman's ρ: 0.21-0.42) over 3 years for As, Ca, Cr, Fe, Pb, Mn, and Zn, and strong correlations (>0.50) for Se, Cu, and Hg. IMPACT STATEMENT: This toenail reliability study found that a low-mass (~25 mg) toenail sample (1-2 clippings) is suitable for the determination of most elements using ICP-MS and helps to increase the analytical capacity of limited toenail biospecimens collected in cohort studies. The results highlight differences in the suitability of toenails for chronic metal exposure assessment by element and underscore the need to consider intra-person variability, especially when comparing results across studies. We also provide recommendations for analytical standardization and the partitioning of the total collected toenail sample into multiple analytic sub-samples for future studies using toenail biospecimen for multiple assays.

Clinical characteristics and overall survival among acute myeloid leukemia patients with TP53 gene mutation or chromosome 17p deletion.

Approximately 5% to 15% of acute myeloid leukemia (AML) patients have TP53 gene mutations (TP53m), which are associated with very poor outcomes. Adults (≥18 years) with a new AML diagnosis were included from a nationwide, de-identified, real-world database. Patients receiving first-line therapy were divided into three cohorts: venetoclax (VEN) + hypomethylating agents (HMAs; Cohort A), intensive chemotherapy (Cohort B), or HMA without VEN (Cohort C). A total of 370 newly diagnosed AML patients with TP53m (n = 124), chromosome 17p deletion (n = 166), or both (n = 80) were included. The median age was 72 years (range, 24-84); most were male (59%) and White (69%). Baseline bone marrow (BM) blasts were ≤30%, 31%-50%, and >50% in 41%, 24%, and 29% of patients in Cohorts A, B, and C, respectively. BM remission (<5% blasts) with first-line therapy was reported in 54% of patients (115/215) overall, and 67% (38/57), 62% (68/110), and 19% (9/48) for respective cohorts (median BM remission duration: 6.3, 6.9, and 5.4 months). Median overall survival (95% CI) was 7.4 months (6.0-8.8) for Cohort A, 9.4 months (7.2-10.4) for Cohort B, and 5.9 months (4.3-7.5) for Cohort C. There were no differences in survival by treatment type after adjusting for the effects of relevant covariates (Cohort A vs. C adjusted hazard ratio [aHR] = 0.9; 95% CI, 0.7-1.3; Cohort A vs. B aHR = 1.0; 95% CI, 0.7-1.5; and Cohort C vs. B aHR = 1.1; 95% CI, 0.8-1.6). Patients with TP53m AML have dismal outcomes with current therapies, demonstrating the high unmet need for improved treatments.

Laboratory and field evaluation of a low-cost methane sensor and key environmental factors for sensor calibration.

Low-cost sensors enable finer-scale spatiotemporal measurements within the existing methane (CH4) monitoring infrastructure and could help cities mitigate CH4 emissions to meet their climate goals. While initial studies of low-cost CH4 sensors have shown potential for effective CH4 measurement at ambient concentrations, sensor deployment remains limited due to questions about interferences and calibration across environments and seasons. This study evaluates sensor performance across seasons with specific attention paid to the sensor's understudied carbon monoxide (CO) interferences and environmental dependencies through long-term ambient co-location in an urban environment. The sensor was first evaluated in a laboratory using chamber calibration and co-location experiments, and then in the field through two 8 week co-locations with a reference CH4 instrument. In the laboratory, the sensor was sensitive to CH4 concentrations below ambient background concentrations. Different sensor units responded similarly to changing CH4, CO, temperature, and humidity conditions but required individual calibrations to account for differences in sensor response factors. When deployed in-field, co-located with a reference instrument near Baltimore, MD, the sensor captured diurnal trends in hourly CH4 concentration after corrections for temperature, absolute humidity, CO concentration, and hour of day. Variable performance was observed across seasons with the sensor performing well (R 2 = 0.65; percent bias 3.12%; RMSE 0.10 ppm) in the winter validation period and less accurately (R 2 = 0.12; percent bias 3.01%; RMSE 0.08 ppm) in the summer validation period where there was less dynamic range in CH4 concentrations. The results highlight the utility of sensor deployment in more variable ambient CH4 conditions and demonstrate the importance of accounting for temperature and humidity dependencies as well as co-located CO concentrations with low-cost CH4 measurements. We show this can be addressed via Multiple Linear Regression (MLR) models accounting for key covariates to enable urban measurements in areas with CH4 enhancement. Together with individualized calibration prior to deployment, the sensor shows promise for use in low-cost sensor networks and represents a valuable supplement to existing monitoring strategies to identify CH4 hotspots.

A Rare Occurrence of Rotational Retro-Esophageal Gastric Body Herniation Through a Nissen Fundoplication.

Anti-reflux procedures have become a mainstay in managing gastroesophageal reflux disease (GERD) and hiatal hernia. Unfortunately, post-operative events such as breakdown of the wrap, downward slippage, or transdiaphragmatic herniation of an intact wrap cause these procedures to fail and create complications such as recurrent hiatal hernia and reflux dysphagia, regurgitation, and obstruction requiring revision surgery. We discuss a case of a rotational retro-esophageal herniation of the gastric body through a Nissen fundoplication presenting as obstruction, dysphagia, and regurgitation, highlighting the peculiar nature of this presentation and the ease of misdiagnosis given its rarity.

Child Disruptions, Remote Learning, and Parent Mental Health during the COVID-19 Pandemic.

New York City (NYC) was an epicenter of the COVID-19 pandemic, which resulted in broad economic, social, and emotional consequences in the lives of individuals. The current study examined associations between pandemic-related stressors and adverse mental health symptoms among NYC parents/caregivers. Community-based participatory research was used to develop a survey, and logistic regression models were utilized to assess associations between factors including disruptions in child routines and remote learning, and parent-reported symptoms of stress, anxiety, depression, and post-traumatic stress disorder (PTSD). Some 91.0% of parents reported stress and 41.2, 26.6, and 33.7% reported symptoms of anxiety, depression, and PTSD, respectively. Most parents (87.6%) reported cancellation of at least one child activity. Of the parents, 60.3% reported that their children participated in remote learning and the majority (70.3%) reported feeling overwhelmed by it. Having more cancelled child activities was associated with higher odds of reported mental health symptoms, with not being able to play outside associated with higher odds of anxiety (1.80 (1.26, 2.58), p = 0.001), depression (1.93 (1.29, 2.91), p = 0.002), PTSD (1.64 (1.13, 2.39), p = 0.009), and stress (2.34 (1.27, 4.44), p = 0.008). Feeling overwhelmed by remote learning was also associated with higher odds of all four outcomes. Pre-existing mental illness, lower resilience scores, and lower socioeconomic status emerged as additional factors associated with symptoms of mental illness. These findings highlight the importance of resources to minimize adverse psychological effects among vulnerable families.

Ephaptic Coupling Is a Mechanism of Conduction Reserve During Reduced Gap Junction Coupling.

Many cardiac pathologies are associated with reduced gap junction (GJ) coupling, an important modulator of cardiac conduction velocity (CV). However, the relationship between phenotype and functional expression of the connexin GJ family of proteins is controversial. For example, a 50% reduction of GJ coupling has been shown to have little impact on myocardial CV due to a concept known as conduction reserve. This can be explained by the ephaptic coupling (EpC) theory whereby conduction is maintained by a combination of low GJ coupling and increased electrical fields generated in the sodium channel rich clefts between neighboring myocytes. At the same time, low GJ coupling may also increase intracellular charge accumulation within myocytes, resulting in a faster transmembrane potential rate of change during depolarization (dV/dt_max) that maintains macroscopic conduction. To provide insight into the prevalence of these two phenomena during pathological conditions, we investigated the relationship between EpC and charge accumulation within the setting of GJ remodeling using multicellular simulations and companion perfused mouse heart experiments. Conduction along a fiber of myocardial cells was simulated for a range of GJ conditions. The model incorporated intercellular variations, including GJ coupling conductance and distribution, cell-to-cell separation in the intercalated disc (perinexal width-WP), and variations in sodium channel distribution. Perfused heart studies having conditions analogous to those of the simulations were performed using wild type mice and mice heterozygous null for the connexin gene Gja1. With insight from simulations, the relative contributions of EpC and charge accumulation on action potential parameters and conduction velocities were analyzed. Both simulation and experimental results support a common conclusion that low GJ coupling decreases and narrowing WP increases the rate of the AP upstroke when sodium channels are densely expressed at the ends of myocytes, indicating that conduction reserve is more dependent on EpC than charge accumulation during GJ uncoupling.

Characterizing spatiotemporal variability in airborne heavy metal concentration: Changes after 18 Years in Baltimore, MD.

INTRODUCTION: This study investigates the impact of changes in local industry, urban development, and proximity to suspected emission sources on airborne metal concentration in Baltimore, Maryland between 2001 and 2019 with particular focus on the urban industrial community of Curtis Bay in South Baltimore. METHODS: Integrated PM2.5 and PM10 Harvard Impactors were set up at six locations in the Baltimore City metropolitan area in weeklong sampling sessions from January-July 2019 to assess variation in airborne metal concentration by proximity to suspected metal emission sources. PM2.5 and PM10 were collected on Teflo filters and analyzed for a panel of 12 metals and metalloids (As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, and Zn) using inductively coupled plasma mass spectrometry. The findings were compared against airborne metal concentrations reported by the Baltimore Supersite in 2001 and 2003 to assess changes over the 18-year period. RESULTS: PM2.5 concentrations reported from this study ranged from 3.27 µg/m3 to 36.0 µg/m3 and PM10 concentrations ranged from 9.00 µg/m3 to 30.1 µg/m3 across all sampling sites. Metal concentrations ranged from 1.4 times (Cd) to 4.8 times (Cr) higher in PM10 compared to PM2.5. Compared to the study reference site, median PM2.5 concentrations of Co and Fe were roughly 1.8 times and 2.1 times higher, respectively, at near-road sampling sites indicating significant variability in airborne metal concentration by proximity to local traffic emissions. PM2.5 and PM10 Sb concentrations were 3.4 times and 6.7 times higher at a near incinerator site compared to the reference, consistent with existing evidence of Sb sourcing from municipal incinerators in Baltimore City. Decreases in Cr (-40%), Ni (-73%), Pb (-55%), and Zn (-36%) concentrations were observed over the 18-year period while concentrations of Cu, Fe, and Mn were not statistically significantly different. CONCLUSION: Declines in airborne Cr, Ni, Pb, and Zn concentration since 2001 appear to coincide with industrial decline highlighting the success of remediation and redevelopment efforts. Remaining spatial variability is related to vehicular traffic and proximity to a municipal incinerator which should be focal areas for future intervention to reduce metal exposure disparities in Baltimore City.

Next Directions in Measurement of the Home Mathematics Environment: An International and Interdisciplinary Perspective.

This article synthesizes findings from an international virtual conference, funded by the National Science Foundation (NSF), focused on the home mathematics environment (HME). In light of inconsistencies and gaps in research investigating relations between the HME and children's outcomes, the purpose of the conference was to discuss actionable steps and considerations for future work. The conference was composed of international researchers with a wide range of expertise and backgrounds. Presentations and discussions during the conference centered broadly on the need to better operationalize and measure the HME as a construct - focusing on issues related to child, family, and community factors, country and cultural factors, and the cognitive and affective characteristics of caregivers and children. Results of the conference and a subsequent writing workshop include a synthesis of core questions and key considerations for the field of research on the HME. Findings highlight the need for the field at large to use multi-method measurement approaches to capture nuances in the HME, and to do so with increased international and interdisciplinary collaboration, open science practices, and communication among scholars.

The conduction velocity-potassium relationship in the heart is modulated by sodium and calcium.

The relationship between cardiac conduction velocity (CV) and extracellular potassium (K+) is biphasic, with modest hyperkalemia increasing CV and severe hyperkalemia slowing CV. Recent studies from our group suggest that elevating extracellular sodium (Na+) and calcium (Ca2+) can enhance CV by an extracellular pathway parallel to gap junctional coupling (GJC) called ephaptic coupling that can occur in the gap junction adjacent perinexus. However, it remains unknown whether these same interventions modulate CV as a function of K+. We hypothesize that Na+, Ca2+, and GJC can attenuate conduction slowing consequent to severe hyperkalemia. Elevating Ca2+ from 1.25 to 2.00 mM significantly narrowed perinexal width measured by transmission electron microscopy. Optically mapped, Langendorff-perfused guinea pig hearts perfused with increasing K+ revealed the expected biphasic CV-K+ relationship during perfusion with different Na+ and Ca2+ concentrations. Neither elevating Na+ nor Ca2+ alone consistently modulated the positive slope of CV-K+ or conduction slowing at 10-mM K+; however, combined Na+ and Ca2+ elevation significantly mitigated conduction slowing at 10-mM K+. Pharmacologic GJC inhibition with 30-µM carbenoxolone slowed CV without changing the shape of CV-K+ curves. A computational model of CV predicted that elevating Na+ and narrowing clefts between myocytes, as occur with perinexal narrowing, reduces the positive and negative slopes of the CV-K+ relationship but do not support a primary role of GJC or sodium channel conductance. These data demonstrate that combinatorial effects of Na+ and Ca2+ differentially modulate conduction during hyperkalemia, and enhancing determinants of ephaptic coupling may attenuate conduction changes in a variety of physiologic conditions.

Effects of yoga on improving quality of life in patients with breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Complications of breast cancer treatment can cause physical and psychosocial distress in patients. Yoga demonstrates substantial potential as a supportive therapy for patients with breast cancer. Our aim is to conduct a meta-analysis of randomized controlled trials to evaluate the effectiveness of yoga in enhancing the quality of life (QoL) of patients with breast cancer. METHODS: We searched for studies published before March 2020 in the PubMed, Embase, and Cochrane Library databases. Individual effect sizes were standardized, and the pooled effect size was calculated using a random effect model. Measured outcomes included QoL, anxiety and depression, stress, fatigue, pain severity, and sleep quality. RESULTS: In total, 26 trials involving 2069 patients were reviewed. Significant enhancement in QoL was observed immediately after the yoga intervention. The pooled mean differences in social (weighted mean difference [WMD]: 1.36, 95% confidence interval [CI] 0.12-2.61), emotional (WMD: 1.46, 95% CI 0.26-2.66), and functional well-being (WMD: 2.04, 95% CI 0.21-3.87) were significantly higher in the yoga group than in the control group. Patients practicing yoga exhibited significant improvements in physical well-being, mental well-being, and sleep quality as well as reductions in anxiety, depression, stress, fatigue, and pain severity after the intervention. CONCLUSIONS: Yoga may enhance QoL in patients with breast cancer experiencing post-treatment complications. Therefore, we recommend yoga as a supportive therapy for patients with breast cancer to relieve post-treatment distress.

Andexanet versus prothrombin complex concentrates: Differences in reversal of factor Xa inhibitors in in vitro thrombin generation.

BACKGROUND: Andexanet alfa (andexanet) is a modified human factor Xa (FXa) approved for anticoagulation reversal in patients with life-threatening bleeding treated with rivaroxaban or apixaban. Four-factor prothrombin complex concentrates (4F-PCCs) are approved for reversal of vitamin K antagonist-induced anticoagulation but not FXa inhibitors. The mechanism and effectiveness of 4F-PCCs for FXa inhibitor reversal are unclear. OBJECTIVE: To investigate the mechanism and impact of 4F-PCCs on reversal of rivaroxaban and apixaban in vitro compared to andexanet. METHODS: The effect of 4F-PCCs (or individual factors) on tissue factor-initiated thrombin generation (TF-TG) was evaluated in human plasma, with or without rivaroxaban or apixaban, and compared with andexanet under the same conditions. RESULTS: In the TF-TG assay, 4F-PCC completely reversed warfarin anticoagulation. Andexanet normalized TF-TG over a wide range of apixaban and rivaroxaban concentrations tested (19-2000 ng/mL). However, 4F-PCC (or individual factors) was unable to normalize endogenous thrombin potential (ETP) or peak thrombin (Peak) in the presence of apixaban or rivaroxaban (75-500 ng/mL). TF-TG was only normalized by 4F-PCC at inhibitor concentrations <75 ng/mL (ETP) or <37.5 ng/mL (Peak). These data can be explained by the estimated thresholds of FXa activity required to support normal TF-TG based on the inhibitor:FXa ratios and levels of uninhibited FXa. The data are consistent with healthy volunteer studies where TF-TG is not normalized until inhibitor levels are substantially decreased. CONCLUSIONS: Both the theoretical calculations and experimental data demonstrated that 4F-PCCs are only able to normalize TG over a low and narrow range of FXa inhibitor concentrations (<75 ng/mL).

Genomic and epigenomic EBF1 alterations modulate TERT expression in gastric cancer.

Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark of cancer, occurring in 90% of human malignancies. However, specific mechanisms driving TERT reactivation remain obscure for many tumor types and in particular gastric cancer (GC), a leading cause of global cancer mortality. Here, through comprehensive genomic and epigenomic analysis of primary GCs and GC cell lines, we identified the transcription factor early B cell factor 1 (EBF1) as a TERT transcriptional repressor and inactivation of EBF1 function as a major cause of TERT upregulation. Abolishment of EBF1 function occurs through 3 distinct (epi)genomic mechanisms. First, EBF1 is epigenetically silenced via DNA methyltransferase, polycomb-repressive complex 2 (PRC2), and histone deacetylase activity in GCs. Second, recurrent, somatic, and heterozygous EBF1 DNA-binding domain mutations result in the production of dominant-negative EBF1 isoforms. Third, more rarely, genomic deletions and rearrangements proximal to the TERT promoter remobilize or abolish EBF1-binding sites, derepressing TERT and leading to high TERT expression. EBF1 is also functionally required for various malignant phenotypes in vitro and in vivo, highlighting its importance for GC development. These results indicate that multimodal genomic and epigenomic alterations underpin TERT reactivation in GC, converging on transcriptional repressors such as EBF1.