Sociodemographic inequities in the burden of carcinogenic industrial air emissions in the United States.

BACKGROUND: Industrial facilities are not located uniformly across communities in the United States, but how the burden of exposure to carcinogenic air emissions may vary across population characteristics is unclear. We evaluated differences in carcinogenic industrial pollution among major sociodemographic groups in the United States and Puerto Rico. METHODS: We evaluated cross-sectional associations of population characteristics including race and ethnicity, educational attainment, and poverty at the census tract level with point-source industrial emissions of 21 known human carcinogens using regulatory data from the US Environmental Protection Agency. Odds ratios and 95% confidence intervals comparing the highest emissions (tertile or quintile) to the referent group (zero emissions [ie, nonexposed]) for all sociodemographic characteristics were estimated using multinomial, population density-adjusted logistic regression models. RESULTS: In 2018, approximately 7.4 million people lived in census tracts with nearly 12 million pounds of carcinogenic air releases. The odds of tracts having the greatest burden of benzene, 1,3-butadiene, ethylene oxide, formaldehyde, trichloroethylene, and nickel emissions compared with nonexposed were 10%-20% higher for African American populations, whereas White populations were up to 18% less likely to live in tracts with the highest emissions. Among Hispanic and Latino populations, odds were 16%-21% higher for benzene, 1,3-butadiene, and ethylene oxide. Populations experiencing poverty or with less than high school education were associated with up to 51% higher burden, irrespective of race and ethnicity. CONCLUSIONS: Carcinogenic industrial emissions disproportionately impact African American and Hispanic and Latino populations and people with limited education or experiencing poverty thus representing a source of pollution that may contribute to observed cancer disparities.

Combined CD25, CD64, and CD69 Biomarker in 3D-Printed Multizone Millifluidic Device for Sepsis Detection in Clinical Samples.

Sepsis is a serious medical condition that arises from a runaway response to an infection, which triggers the immune system to release chemicals into the bloodstream. This immune response can result in widespread inflammation throughout the body, which may cause harm to vital organs and, in more severe cases, lead to organ failure and death. Timely and accurate diagnosis of sepsis remains a challenge in analytical diagnostics. In this work, we have developed and validated a sepsis detection device, utilizing 3D printing technology, which incorporates multiple affinity separation zones. Our device requires minimal operator intervention and utilizes CD64, CD69, and CD25 as the biomarker targets for detecting sepsis in liquid biopsies. We assessed the effectiveness of our 3D-printed multizone cell separation device by testing it on clinical samples obtained from both septic patients (n = 35) and healthy volunteers (n = 8) and validated its performance accordingly. Unlike previous devices using poly(dimethyl siloxane), the 3D-printed device had reduced nonspecific binding for anti-CD25 capture, allowing this biomarker to be assayed for the first time in cell separations. Our results showed a statistically significant difference in cell capture between septic and healthy samples (with p values of 0.0001 for CD64, CD69, and CD25), suggesting that 3D-printed multizone cell capture is a reliable method for distinguishing sepsis. A receiver operator characteristic (ROC) analysis was performed to determine the accuracy of the captured cell counts for each antigen in detecting sepsis. The ROC area under the curve (AUC) values for on-chip detection of CD64+, CD69+, and CD25+ leukocytes were 0.96, 0.92, and 0.88, respectively, indicating our diagnostic test matches clinical outcomes. When combined for sepsis diagnosis, the AUC value for CD64, CD69, and CD25 was 0.99, indicating an improved diagnostic performance due to the use of multiple biomarkers.

Residues of an anthelmintic veterinary drug (closantel) detected in red foxes (Vulpes vulpes) in Scotland.

The contamination of the environment by some veterinary medicines and their impact on wild animals is of increasing concern. However, there is a lack of information about their residues in wildlife. The sentinel animals most commonly used for monitoring the level of environmental contamination are birds of prey, and information on other carnivores and scavengers scarce. This study examined the livers from 118 foxes for residues of a range of 18 veterinary medicines (16 anthelmintic agents and 2 metabolites) used on farm livestock. The samples were collected from foxes, primarily in Scotland, shot during legal pest control activities conducted between 2014 and 2019. Closantel residues were detected in 18 samples, and the concentrations found ranged from 6.5 µgkg-1 to 1383 µgkg-1. No other compounds were found in significant quantities. The results show a surprising frequency and level of closantel contamination, raising concerns about both the route of contamination and the potential impacts on wild animals and the environment, such as the potential for significant wildlife contamination to contribute to the development of closantel-resistant parasites. The results also suggest that red fox (Vulpes vulpes) could be a useful sentinel species for detecting and monitoring some veterinary medicine residues in the environment.

The most commonly injured nerves at surgery: A comprehensive review.

Iatrogenic nerve injury during surgery is a major source of concern for both patients and surgeons. This study aimed to identify the nerves most commonly injured during surgery, along with the commonly associated operative procedures. A literature search was conducted using the PubMed database to identify nerves commonly injured during surgery, along with the surgical procedure associated with the injury. The following 11 nerves, ranked in order with their associated surgical procedures, were found to be the most commonly injured: (a) intercostobrachial nerve in axillary lymph node dissections and transaxillary breast augmentations, (b) vestibulocochlear nerve in cerebellopontine tumor resections and vestibular schwannoma removals, c) facial nerve in surgeries of the inner ear and cheek region, (d) long thoracic nerve in axillary lymph node dissections, (e) spinal accessory nerve in surgeries of the posterior triangle of the neck and cervical lymph node biopsies, (f) recurrent laryngeal nerve in thyroid surgeries, (g) genitofemoral nerve in inguinal hernia and varicocele surgeries, (h) sciatic nerve in acetabular fracture repairs and osteotomies, (i) median nerve in carpal tunnel release surgeries, (j) common fibular nerve in varicose vein and short saphenous vein surgeries, and (k) ulnar nerve in supracondylar fracture surgeries. Although the root cause of iatrogenic nerve injury differs for each nerve, there are four unifying factors that could potentially decrease this risk for all peripheral nerves. These four influencing factors include knowledge of potential anatomical variations, visual identification of at-risk nerves during the procedure, intraoperative nerve monitoring, and expertise of the surgeon.

Multi-residue determination of anticoagulant rodenticides in vertebrate wildlife and domestic animals using Ultra (High) Performance Liquid Chromatography Tandem Mass Spectrometry.

Anticoagulant rodenticide (AR) products are used globally to control rodent pests in domestic, urban, agricultural and industrial environments. However, there is a substantial volume of evidence that non-target vertebrate wildlife i.e. predators and scavengers in particular and other animals, are vulnerable to contamination via direct or indirect routes of exposure. The determination of multiple AR residues in liver tissue samples that can range from remnants of a small bird of prey liver to an intact liver from a large mammal is complicated as residue levels encountered can vary considerably too. So, the utilisation of ultra-sensitive systems has to be carefully considered in order to allow routine application of the method to all sample compositions presented for analysis. The UHPLC-MSMS method described now: •permits quantitative analysis of ultra-low levels of multiple-residues (0.0025-1 mg kg-1) in a single experiment.•uses the same U(H)PLC column for the determination of AR and multiple-pesticide residue in similar specimens.•allows higher sample throughput due to shaking rather than tumbling of samples during the extraction procedure.

Rate of exposure of a sentinel species, invasive American mink (Neovison vison) in Scotland, to anticoagulant rodenticides.

Anticoagulant rodenticides (ARs) are highly toxic compounds that are exclusively used for the control of rodent pests. Despite their defined use, they are nonetheless found in a large number of non-target species indicating widespread penetration of wildlife. Attempts to quantify the scale of problem are complicated by non-random sampling of individuals tested for AR contamination. The American mink (Neovison vison) is a wide ranging, non-native, generalist predator that is subject to wide scale control efforts in the UK. Exposure to eight ARs was determined in 99 mink trapped in NE Scotland, most of which were of known age. A high percentage (79%) of the animals had detectable residues of at least one AR, and more than 50% of the positive animals had two or more ARs. The most frequently detected compound was bromadiolone (75% of all animals tested), followed by difenacoum (53% of all mink), coumatetralyl (22%) and brodifacoum (9%). The probability of mink exposure to ARs increased by 4.5% per month of life, and was 1.7 times higher for mink caught in areas with a high, as opposed to a low, density of farms. The number of AR compounds acquired also increased with age and with farm density. No evidence was found for sexual differences in the concentration and number of ARs. The wide niche and dietary overlap of mink with several native carnivore species, and the fact that American mink are culled for conservation throughout Europe, suggest that this species may act as a sentinel species, and the application of these data to other native carnivores is discussed.

Soil-plant N processes in a High Arctic ecosystem, NW Greenland are altered by long-term experimental warming and higher rainfall.

Rapid temperature and precipitation changes in High Arctic tundra ecosystems are altering the biogeochemical cycles of carbon (C) and nitrogen (N), but in ways that are difficult to predict. The challenge grows from the uncertainty of N cycle responses and the extent to which shifts in soil N are coupled with the C cycle and productivity of tundra systems. We used a long-term (since 2003) experiment of summer warming and supplemental summer water additions to a High Arctic ecosystem in NW Greenland, and applied a combination of discrete sampling and in situ soil core incubations to measure C and N pools and seasonal microbial processes that might control plant-available N. We hypothesized that elevated temperature and increased precipitation would stimulate microbial activity and net inorganic N mineralization, thereby increasing plant N-availability through the growing season. While we did find increased N mineralization rates under both global change scenarios, water addition also significantly increased net nitrification rates, loss of NO3 (-) -N via leaching, and lowered rates of labile organic N production. We also expected the chronic warming and watering would lead to long-term changes in soil N-cycling that would be reflected in soil δ(15) N values. We found that soil δ(15) N decreased under the different climate change scenarios. Our results suggest that temperature accelerates biological processes and existing C and N transformations, but moisture increases soil hydraulic connectivity and so alters the pathways, and changes the fate of the products of C and N transformations. In addition, our findings indicate that warmer, wetter High Arctic tundra will be cycling N and C in ways that may transform these landscapes in part leading to greater C sequestration, but simultaneously, N losses from the upper soil profile that may be transported to depth dissolved in water and or transported off site in lateral flow.

Complex carbon cycle responses to multi-level warming and supplemental summer rain in the high Arctic.

The Arctic has experienced rapid warming and, although there are uncertainties, increases in precipitation are projected to accompany future warming. Climate changes are expected to affect magnitudes of gross ecosystem photosynthesis (GEP), ecosystem respiration (ER) and the net ecosystem exchange of CO2 (NEE). Furthermore, ecosystem responses to climate change are likely to be characterized by nonlinearities, thresholds and interactions among system components and the driving variables. These complex interactions increase the difficulty of predicting responses to climate change and necessitate the use of manipulative experiments. In 2003, we established a long-term, multi-level and multi-factor climate change experiment in a polar semidesert in northwest Greenland. Two levels of heating (30 and 60 W m(-2) ) were applied and the higher level was combined with supplemental summer rain. We made plot-level measurements of CO2 exchange, plant community composition, foliar nitrogen concentrations, leaf δ(13) C and NDVI to examine responses to our treatments at ecosystem- and leaf-levels. We confronted simple models of GEP and ER with our data to test hypotheses regarding key drivers of CO2 exchange and to estimate growing season CO2 -C budgets. Low-level warming increased the magnitude of the ecosystem C sink. Meanwhile, high-level warming made the ecosystem a source of C to the atmosphere. When high-level warming was combined with increased summer rain, the ecosystem became a C sink of magnitude similar to that observed under low-level warming. Competition among our ER models revealed the importance of soil moisture as a driving variable, likely through its effects on microbial activity and nutrient cycling. Measurements of community composition and proxies for leaf-level physiology suggest GEP responses largely reflect changes in leaf area of Salix arctica, rather than changes in leaf-level physiology. Our findings indicate that the sign and magnitude of the future High Arctic C budget may depend upon changes in summer rain.

Association of differentiation state of CD4+ T cells and disease progression in HIV-1 perinatally infected children.

BACKGROUND: In the USA, most HIV-1 infected children are on antiretroviral drug regimens, with many individuals surviving through adolescence and into adulthood. The course of HIV-1 infection in these children is variable, and understudied. METHODOLOGY/PRINCIPAL FINDINGS: We determined whether qualitative differences in immune cell subsets could explain a slower disease course in long term survivors with no evidence of immune suppression (LTS-NS; CD4%≥25%) compared to those with severe immune suppression (LTS-SS; CD4%≤15%). Subjects in the LTS-NS group had significantly higher frequencies of naïve (CCR7+CD45RA+) and central memory (CCR7+CD45RA-) CD4+ T cells compared to LTS-SS subjects (p = 0.0005 and <0.0001, respectively). Subjects in the rapid progressing group had significantly higher levels of CD4+ T(EMRA) (CCR7-CD45RA+) cells compared to slow progressing subjects (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Rapid disease progression in vertical infection is associated with significantly higher levels of CD4+ T(EMRA) (CCR7-CD45RA+) cells.

Identification of human endogenous retrovirus-specific T cell responses in vertically HIV-1-infected subjects.

Human endogenous retrovirus (HERV)-specific T cell responses in HIV-1-infected adults have been reported. Whether HERV-specific immunity exists in vertically HIV-1-infected children is unknown. We performed a cross-sectional analysis of HERV-specific T cell responses in 42 vertically HIV-1-infected children. HERV (-H, -K, and -L family)-specific T cell responses were identified in 26 of 42 subjects, with the greatest magnitude observed for the responses to HERV-L. These HERV-specific T cell responses were inversely correlated with the HIV-1 plasma viral load and positively correlated with CD4(+) T cell counts. These data indicate that HERV-specific T cells may participate in controlling HIV-1 replication and that certain highly conserved HERV-derived proteins may serve as promising therapeutic vaccine targets in HIV-1-infected children.

Immunodominance of HIV-1 specific CD8+ T-cell responses is related to disease progression rate in vertically infected adolescents.

BACKGROUND: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups. CONCLUSIONS/SIGNIFICANCE: Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions.

Sequential formation of ion pairs during activation of a sodium channel voltage sensor.

Electrical signaling in biology depends upon a unique electromechanical transduction process mediated by the S4 segments of voltage-gated ion channels. These transmembrane segments are driven outward by the force of the electric field on positively charged amino acid residues termed "gating charges," which are positioned at three-residue intervals in the S4 transmembrane segment, and this movement is coupled to opening of the pore. Here, we use the disulfide-locking method to demonstrate sequential ion pair formation between the fourth gating charge in the S4 segment (R4) and two acidic residues in the S2 segment during activation. R4 interacts first with E70 at the intracellular end of the S2 segment and then with D60 near the extracellular end. Analysis with the Rosetta Membrane method reveals the 3-D structures of the gating pore as these ion pairs are formed sequentially to catalyze the S4 transmembrane movement required for voltage-dependent activation. Our results directly demonstrate sequential ion pair formation that is an essential feature of the sliding helix model of voltage sensor function but is not compatible with the other widely discussed gating models.

Cross-sectional dating of novel haplotypes of HERV-K 113 and HERV-K 115 indicate these proviruses originated in Africa before Homo sapiens.

The human genome, human endogenous retroviruses (HERV), of which HERV-K113 and HERV-K115 are the only known full-length proviruses that are insertionally polymorphic. Although a handful of previously published papers have documented their prevalence in the global population; to date, there has been no report on their prevalence in the United States population. Here, we studied the geographic distribution of K113 and K115 among 156 HIV-1+ subjects from the United States, including African Americans, Hispanics, and Caucasians. In the individuals studied, we found higher insertion frequencies of K113 (21%) and K115 (35%) in African Americans compared with Caucasians (K113 9% and K115 6%) within the United States. We also report the presence of three single nucleotide polymorphism sites in the K113 5' long terminal repeats (LTRs) and four in the K115 5' LTR that together constituted four haplotypes for K113 and five haplotypes for K115. HERV insertion times can be estimated from the sequence differences between the 5' and 3' LTR of each insertion, but this dating method cannot be used with HERV-K115. We developed a method to estimate insertion times by applying coalescent inference to 5' LTR sequences within our study population and validated this approach using an independent estimate derived from the genetic distance between K113 5' and 3' LTR sequences. Using our method, we estimated the insertion dates of K113 and K115 to be a minimum of 800,000 and 1.1 million years ago, respectively. Both these insertion dates predate the emergence of anatomically modern Homo sapiens.

"Changing for my kid": fatherhood experiences of Mexican-origin teen fathers involved in the justice system.

A descriptive phenomenological study was conducted with six adolescent fathers of Mexican origin on juvenile probation for a variety of serious offenses. All participants successfully completed a parenting program designed especially for teen fathers. In a series of consecutive in-depth interviews, teen fathers were asked to discuss their experiences as fathers. Four phenomena were identified from the data: (a) not giving up and deciding to be a dad, (b) figuring out my relationships after becoming a father, (c) wanting to be a good father, and (d) wanting to be Brown and a father. Findings challenge negative stereotypes associated with Mexican-origin teen fathers engaged in delinquent behaviors and describe the ways in which fatherhood became an important positive motivator in the lives of participants.

Functional properties and differential neuromodulation of Na(v)1.6 channels.

The voltage-gated sodium channel Na(v)1.6 plays unique roles in the nervous system, but its functional properties and neuromodulation are not as well established as for Na(V)1.2 channels. We found no significant differences in voltage-dependent activation or fast inactivation between Na(V)1.6 and Na(V)1.2 channels expressed in non-excitable cells. In contrast, the voltage dependence of slow inactivation was more positive for Na(v)1.6 channels, they conducted substantially larger persistent sodium currents than Na(v)1.2 channels, and they were much less sensitive to inhibition by phosphorylation by cAMP-dependent protein kinase and protein kinase C. Resurgent sodium current, a hallmark of Na(v)1.6 channels in neurons, was not observed for Na(V)1.6 expressed alone or with the auxiliary beta(4) subunit. The unique properties of Na(V)1.6 channels, together with the resurgent currents that they conduct in neurons, make these channels well-suited to provide the driving force for sustained repetitive firing, a crucial property of neurons.

Single-cell, phosphoepitope-specific analysis demonstrates cell type- and pathway-specific dysregulation of Jak/STAT and MAPK signaling associated with in vivo human immunodeficiency virus type 1 infection.

Despite extensive evidence of cell signaling alterations induced by human immunodeficiency virus type 1 (HIV-1) in vitro, the relevance of these changes to the clinical and/or immunologic status of HIV-1-infected individuals is often unclear. As such, mapping the details of cell type-specific degradation of immune function as a consequence of changes to signaling network responses has not been readily accessible. We used a flow cytometric-based assay of signaling to determine Janus kinase/signal transducers and activators of transcription (Jak/STAT) signaling changes at the single-cell level within distinct cell subsets from the primary immune cells of HIV-1-infected donors. We identified a specific defect in granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven Stat5 phosphorylation in the monocytes of HIV-1+ donors. This inhibition was statistically significant in a cohort of treated and untreated individuals. Ex vivo Stat5 phosphorylation levels varied among HIV-1+ donors but did not correlate with CD4(+) T-cell counts or HIV-1 plasma viral load. Low Stat5 activation occurred in HIV-1-infected donors despite normal GM-CSF receptor levels. Investigation of mitogen-activated protein kinase (MAPK) pathways, also stimulated by GM-CSF, led to the observation that lipopolysaccharide-stimulated extracellular signal-regulated kinase phosphorylation is enhanced in monocytes. Thus, we have identified a specific, imbalanced monocyte signaling profile, with inhibition of STAT and enhancement of MAPK signaling, associated with HIV-1 infection. This understanding of altered monocyte signaling responses that contribute to defective antigen presentation during HIV-1 infection could lead to immunotherapeutic approaches that compensate for the deficiency.

HIV-1/HSV-2 co-infected adults in early HIV-1 infection have elevated CD4+ T cell counts.

INTRODUCTION: HIV-1 is often acquired in the presence of pre-existing co-infections, such as Herpes Simplex Virus 2 (HSV-2). We examined the impact of HSV-2 status at the time of HIV-1 acquisition for its impact on subsequent clinical course, and total CD4+ T cell phenotypes. METHODS: We assessed the relationship of HSV-1/HSV-2 co-infection status on CD4+ T cell counts and HIV-1 RNA levels over time prior in a cohort of 186 treatment naïve adults identified during early HIV-1 infection. We assessed the activation and differentiation state of total CD4+ T cells at study entry by HSV-2 status. RESULTS: Of 186 recently HIV-1 infected persons, 101 (54%) were sero-positive for HSV-2. There was no difference in initial CD8+ T cell count, or differences between the groups for age, gender, or race based on HSV-2 status. Persons with HIV-1/HSV-2 co-infection sustained higher CD4+ T cell counts over time (+69 cells/ul greater (SD = 33.7, p = 0.04) than those with HIV-1 infection alone (Figure 1), after adjustment for HIV-1 RNA levels (-57 cells per 1 log(10) higher HIV-1 RNA, p<0.0001). We did not observe a relationship between HSV-2 infection status with plasma HIV-1 RNA levels over time. HSV-2 acquisition after HIV-1 acquisition had no impact on CD4+ count or viral load. We did not detect differences in CD4+ T cell activation or differentiation state by HSV-2+ status. DISCUSSION: We observed no effect of HSV-2 status on viral load. However, we did observe that treatment naïve, recently HIV-1 infected adults co-infected with HSV-2+ at the time of HIV-1 acquisition had higher CD4+ T cell counts over time. If verified in other cohorts, this result poses a striking paradox, and its public health implications are not immediately clear.

"Wanting to be a good father": experiences of adolescent fathers of Mexican descent in a teen fathers program.

Adolescent fatherhood has received limited attention in research and clinical practice. This article describes the design and implementation of a parenting program for adolescent fathers, largely minority, involved in the juvenile justice system. In the teen fathers groups, adolescent fathers were exposed to therapeutic (e.g., family-of-origin) as well as psychoeducational (e.g., child development and parenting) interventions. Findings from a descriptive phenomenological study with six former group participants indicate that the program is an effective way of assisting teen fathers in increasing their commitment as fathers as well as their involvement with their children.