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We previously reported that dibenzo[ a,l]pyrene (DB[ a,l]P), the most potent known environmental carcinogen among polycyclic aromatic hydrocarbons (PAH) congeners, is carcinogenic in the oral tissues of mice. We have now developed a new mouse model which employs the oral application of the fjord region diol epoxide, (±)- anti−11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[ a,l]pyrene (DB[ a,l]PDE), a metabolite of the tobacco smoke constituent DB[ a,l]P, and we show its specific induction of oral squamous cell carcinoma (OSCC) in both tongue and other oral tissues. Groups of B6C3F1 mice (20/group) received 6 or 3 nmol of (±)- anti-DB[ a,l]PDE administered into the oral cavity; 3 times per week for 38 weeks. Additional groups received the vehicle alone or were left untreated. Mice were sacrificed 42 weeks after the first carcinogen administration. The high dose induced 74 and 100% OSCC in the tongue and other oral tissues, respectively; the corresponding values at the lower dose were 45 and 89%. Using immunohistochemistry, we showed that DB[ a,l]PDE resulted in overexpression of p53 and COX-2 proteins in malignant tissues when compared to normal oral tissues and tongues. Consistent with the carcinogenicity, we demonstrated powerful mutagenicity in cII gene in B6C3F1 (Big Blue) mouse tongue. The mutational profile in lacI reporter gene is similar to those detected in human head and neck cancer, and p53 mutations were observed in mouse oral tumor tissues. Taken together, we conclude that the formation of diol epoxides plays a major role among the mechanisms by which DB[ a,l]P exerts its oral mutagenicity and tumorigenicity. [ABSTRACT FROM AUTHOR]

Awad AS, Gao T, Gvritishvili A, You H, Liu Y, Cooper TK, Reeves WB, Tombran-Tink J. Protective role of small pigment epithelium-derived factor (PEDF) peptide in diabetic renal injury. Am J Physiol Renal Physiol 305: F891-F900, 2013. First published July 24, 2013; doi:10.1152/ajprenal.00149.2013.--Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, antioxidative, and anti-inflammatory properties. PEDF is involved in the pathogenesis of diabetic retinopathy, but its direct role in the kidneys remains unclear. We hypothesize that a PEDF fragment (P78-PEDF) confers kidney protection in diabetic nephropathy (DN). The localization of the full-length PEDF protein were determined in DBA mice following multiple low doses of streptozotocin. Using immunohistochemistry, PEDF was localized in the kidney vasculature, interstitial space, glomeruli, tubules, and renal medulla. Kidney PEDF protein and mRNA expression were significantly reduced in diabetic mice. Continuous infusion of P78-PEDF for 6 wk resulted in protection from diabetic neuropathy as indicated by reduced albuminuria and blood urea nitrogen, increased nephrin expression, decreased kidney macrophage recruitment and inflammatory cytokines, and reduced histological changes compared with vehicle-treated diabetic mice. In vitro, P78-PEDF blocked the increase in podocyte permeability to albumin and disruption of the actin cytoskeleton induced by puromycin aminonucleoside treatment. These findings highlight the importance of P78-PEDF peptide as a potential therapeutic modality in early phase diabetic renal injury. [ABSTRACT FROM AUTHOR]

This article responds to current critiques of Ulrich Beck's ‘risk society’ thesis by historians of science and medicine. Those who have engaged with the concept of risk society have been content to accept the fundamental categories of Beck's analysis. In contrast, we argue that Beck's risk society thesis underplays two key themes. First, the role of capitalist social relations as the driver of technological change and the transformation of everyday life; and second, the ways in which hegemonic discourses of risk can be appropriated and transformed by counter-hegemonic forces. In place of ‘risk society’, we propose an approach based upon a ‘political ecology of risk’, which emphasises the social relations that are fundamental to the everyday politics of environmental health. [ABSTRACT FROM PUBLISHER]

Repeated bolus intravenous (IV) administration of large doses of beta-lactams and aminoglycosides has previously been associated with the development of eosinophilic and occlusive arterial lesions limited to the lungs in calves. Reviewing 13 years worth of records from left ventricular assist device implantation studies, morphologically identical segmental arterial lesions were present in 32 of the 56 calves receiving IV antibiotics, affecting lungs (6/50), kidneys (12/56), or lungs and kidneys (14/50). In 16 of these calves, renal arterial lesions spatially colocalized with renal cortical infarctions. Lesions were noted in additional abdominal organs in 4 of the 50 calves and were exclusively present in the liver in a single calf. Similar arterial lesions were also noted in the lungs (3/4), kidneys (1/4), liver (1/4), and spleen (1/4) of unimplanted calves receiving similar IV antibiotic regimens for bacterial infections. Lesions were observed with therapeutic IV doses of cephalosporins with or without aminoglycosides over shorter intervals than previously implicated. Lesions were significantly associated with increased peripheral eosinophil counts and mildly elevated, not reduced, arterial pulse pressures. This report documents the features of an idiosyncratic drug reaction with features strongly suggestive of an acute type-I hypersensitivity in this species. [ABSTRACT FROM AUTHOR]

The article discusses a study on the association of atypical croup with airway lesions, croup and esophagitis. It informs that croup is respiratory illness in children in which cough, inspiratory stridor, hoarseness and respiratory distress occurs. Airway lesions are found in 39 percent cases of airway endoscopies and are accompanied with allergy and gastrointestinal investigations.

Cancer of the oral cavity is a serious disease, affecting about 30,000 individuals in US annually. There are several animal models of oral cancer, but each has certain disadvantages. As a new model, we investigated whether topical application of the tobacco smoke carcinogen, dibenzo[ a,l]pyrene (DB[ a,l]P) is mutagenic and carcinogenic in the oral cavity of the B6C3F1 lacI and B6C3F1 mouse, respectively. B6C3F1 lacI mice received DB[ a,l]P (0, 3, 6, 12 nmol) 3× per week. B6C3F1 mice received the same doses and also 24 nmol. At 38 weeks mutagenesis was measured in oral tissues in lacI mice. For the high dose group, the mutant fraction (MF) in upper mucosa and tongue increased about twofold relative to that in vehicle-alone. The increases were statistically significant. The mutational profile in the DB[ a,l]P-induced mutants was compared with that induced by benzo[ a]pyrene (BaP) in oral tissue. BaP is mutagenic in many tissues when administered by gavage. The mutational profile for DB[ a,l]P was more similar to that reported for p53 mutations in head and neck cancers than was that of BaP. At 47 weeks, oral squamous cell carcinomas (OSCC) were found in 31% of the high-dose B6C3F1 group. Elevations of p53 and COX-2 protein were observed in tumor and dysplastic tissue. As DB[ a,l]P induces mutations and tumors in the oral cavity, and has a mutational profile in oral tissue similar to that found in p53 in human OSCC, the treatment protocol described here may represent a new and relevant model for cancer of the oral cavity. [ABSTRACT FROM AUTHOR]

Here we have investigated whether inhibition of c-Fos expression in RKO human colon carcinoma cells (HCCCs) would result in reduced TGFβ1 expression and suppression of tumor growth in athymic mice. We stably transfected RKO cells with c-Fos small interfering RNA (siRNA) or with the corresponding control siRNA. Using these stable cell lines, we demonstrated that siRNA-c- Fos significantly suppressed both AP-1 binding, promoter reporter activity at the proximal AP-1 site in the TGFβ1 promoter, and TGFβ1 production. Further, we established colon cancer xenografts with each of RKO-siRNA-EV, RKO-siRNA-Ctrl and RKO-siRNA- c-Fos cells. By 24 days, the tumor size of RKO-siRNA-c-Fos xenografts was 40% that of either RKO-EV or RKO-siRNA-Ctrl. Immunohistochemistry (IHC) of tumor xenografts demonstrated that siRNA-c-Fos significantly blocked c-Fos expression, and consequently expression of TGFβ1. However, expression of TGFβ2 and TGFβ3 were unaffected. Overall, our results demonstrate that blockade of TGFβ1 production by siRNA-c-Fos effectively suppressed tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Approximately one quarter of zooxanthellate coral species have a depth distribution from shallow waters (<30 m) down to mesophotic depths of 30-60 m. The deeper populations of such species are less likely to be affected by certain environmental perturbations, including high temperature/high irradiance causing coral bleaching. This has led to the hypothesis that deep populations may serve as refuges and a source of recruits for shallow reef habitats. The extent of vertical connectivity of reef coral species, however, is largely unquantified. Using 10 coral host microsatellite loci and sequences of the host mtDNA putative control region, as well as ribosomal DNA (rDNA) ITS2 sequences of the coral's algal endosymbionts ( Symbiodinium), we examine population structure, connectivity and symbiont specificity in the brooding coral Seriatopora hystrix across a depth profile in both northwest (Scott Reef) and northeast Australia (Yonge Reef). Strong genetic structuring over depth was observed in both regions based on the microsatellite loci; however, Yonge Reef exhibited an additional partitioning of mtDNA lineages (associated with specific symbiont ITS2 types), whereas Scott Reef was dominated by a single mtDNA lineage (with no apparent host-symbiont specificity). Evidence for recruitment of larvae of deep water origin into shallow habitats was found at Scott Reef, suggesting that recovery of shallow water habitats may be aided by migration from deep water refuges. Conversely, no migration from the genetically divergent deep slope populations into the shallow habitats was evident at Yonge Reef, making recovery of shallow habitats from deeper waters at this location highly unlikely. [ABSTRACT FROM AUTHOR]

Temporal and spatial variation in the growth parameters skeletal density, linear extension and calcification rate in massive Porites from two nearshore regions of the northern Great Barrier Reef (GBR) were examined over a 16-year study period. Calcification rates in massive Porites have declined by approximately 21% in two regions on the GBR ∼450 km apart. This is a function primarily of a decrease in linear extension (∼16%) with a smaller decline in skeletal density (∼6%) and contrasts with previous studies on the environmental controls on growth of massive Porites on the GBR. Changes in the growth parameters were linear over time. Averaged across colonies, skeletal density declined over time from 1.32 g cm−3 (SE = 0.017) in 1988 to 1.25 g cm−3 (0.013) in 2003, equivalent to 0.36% yr−1 (0.13). Annual extension declined from 1.52 cm yr−1 (0.035) to 1.28 cm yr−1 (0.026), equivalent to 1.02% yr−1 (0.39). Calcification rates (the product of skeletal density and annual extension) declined from 1.96 g cm−2 yr−1 (0.049) to 1.59 g cm−2 yr−1 (0.041), equivalent to 1.29% yr−1 (0.30). Mean annual seawater temperatures had no effect on skeletal density, but a modal effect on annual extension and calcification with maxima at ∼26.7 °C. There were minor differences in the growth parameters between regions. A decline in coral calcification of this magnitude with increasing seawater temperatures is unprecedented in recent centuries based on analysis of growth records from long cores of massive Porites. We discuss the decline in calcification within the context of known environmental controls on coral growth. Although our findings are consistent with studies of the synergistic effect of elevated seawater temperatures and pCO2 on coral calcification, we conclude that further data on seawater chemistry of the GBR are required to better understand the links between environmental change and effects on coral growth. [ABSTRACT FROM AUTHOR]

Abstract: Computer modelling techniques were used to elucidate the hydration behaviour of three iron (hydr)oxide minerals at the atomic level: white rust, goethite and hematite. A potential model was first adapted and tested against the bulk structures and properties of eight different iron oxides, oxyhydroxides and hydroxides, followed by surface simulations of Fe(OH)2, α-FeO(OH) and α-Fe2O3. The major interaction between the adsorbing water molecules and the surface is through interaction of their oxygen ions with surface iron ions, followed by hydrogen-bonding to surface oxygen ions. The energies released upon the associative adsorption of water range from 1 to 17kJmol−1 for Fe(OH)2, 26 to 80kJmol−1 for goethite and 40 to 85kJmol−1 for hematite, reflecting the increasing oxidation of the iron mineral. Dissociative adsorption at goethite and hematite surfaces releases larger hydration energies, ranging from 120 to 208kJmol−1 for goethite and 76 to 190kJmol−1 for hematite. The thermodynamic morphologies of the minerals, based on the calculated surface energies, agree well with experimental morphologies, where these are available. When the partial pressures required for adsorption of water from the gas phase are plotted against temperature for the goethite and hematite surfaces, taking into account experimental entropies for water, it appears that these minerals may well be instrumental in the retention of water during the cyclic variations in the atmosphere of Mars. [Copyright &y& Elsevier]

Abstract: Atomistic simulation techniques were used to study two sodium sulphate (Na2SO4) polymorphs, phases III and V (thenardite). A new polarisable interatomic potential model for Na2SO4 was derived and used to calculate the uptake and segregation of Ca2+, Mg2+ and K+ impurities in the two phases and their effect on the equilibrium morphologies of the crystals. The lattice energies of the two phases reflect their experimental relative stabilities and the hydrated morphologies express the experimentally found surfaces. In agreement with experiment, calcium is preferentially substituted for sodium in phase III rather than phase V, as is potassium but to a lesser extent. Magnesium substitution is energetically unfavourable in both polymorphs due to the considerably smaller size of the magnesium ion compared to sodium. In general, the impurity ions remain at the surfaces of both polymorphs, rather than segregate into the bulk material, unless the impurities are adsorbed into very stable surfaces, when they do tend to segregate into the bulk. [Copyright &y& Elsevier]

Hemorrhagic smallpox, caused by variola virus (VARV), was a rare but nearly 100% lethal human disease manifestation. Hemorrhagic smallpox is frequently characterized by secondary bacterial infection, coagulopathy, and myocardial and subendocardial hemorrhages. Previous experiments have demonstrated that intravenous (IV) cowpox virus (CPXV) exposure of macaques mimics human hemorrhagic smallpox. The goal of this experiment was to further understand the onset, nature, and severity of cardiac pathology and how it may contribute to disease. The findings support an acute late-stage myocarditis with lymphohistiocytic infiltrates in the CPXV model of hemorrhagic smallpox. [ABSTRACT FROM AUTHOR]

Objective: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation.Study Design: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks.Results: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003).Conclusions: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life.Trial Registration: Clinicaltrials.gov: NCT03192839. [ABSTRACT FROM AUTHOR]

Ongoing Ebola virus disease outbreaks in the Democratic Republic of the Congo follow the largest recorded outbreak in Western Africa (2013–2016). To combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. Here we present Ebola virus disease kinetics in 24 Chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available Kikwit Ebola virus Filovirus Animal Non-Clinical Group (FANG) stock. Until reaching predetermined clinical disease endpoint criteria, six animals underwent anesthesia for repeated clinical sampling and were compared to six that did not. Groups of three animals were euthanized and necropsied on days 3, 4, 5, and 6 post-exposure, respectively. In addition, three uninfected animals served as controls. Here, we present detailed characterization of clinical and laboratory disease kinetics and complete blood counts, serum chemistries, Ebola virus titers, and disease kinetics for future medical countermeasure (MCM) study design and control data. We measured no statistical difference in hematology, chemistry values, or time to clinical endpoint in animals that were anesthetized for clinical sampling during the acute disease compared to those that were not. [ABSTRACT FROM AUTHOR]

To compare the frequency and type of diagnoses associated with pharyngeal dysfunction (PD) in children presenting with early versus late onset sleep disordered breathing (SDB). This was a retrospective, cross-sectional study. A consecutive series of children ≤3 years old who underwent management for SDB were retrospectively identified from a prospectively kept surgical database. The early onset group was compared with two separate late onset (≥4years old) groups. Diagnoses associated with PD included gastroesophageal reflux disease (GERD), swallowing dysfunction, prematurity, asthma, and obesity. Distribution of PD diagnoses, airway lesions, syndromic conditions, pulse oximetry scores, and endoscopic pattern of airway obstruction were compared. 73 patients with early onset SDB were identified (51 boys, mean age 2.25 ± 0.64 years, range 1.75–3 years) and compared with two groups of later onset SDB consisting of 75 and 72 patients with mean ages of 7.58 ± 2.40 years and 8.04 ± 3.34 years respectively (range 4–16 years). The early onset SDB group had a higher prevalence of PD diagnoses compared to the later onset group with 35 of 73 patients being diagnosed compared to 41 of 147 children (p = 0.01). Early onset SDB patients were more likely to have GERD or swallowing dysfunction (p < 0.01) while later onset patients more commonly presented with associated asthma or obesity (p < 0.01). There was no statistically significant difference in airway lesions between groups. Early-onset SDB is associated with conditions causing PD more often than later-onset SDB. Identifying these conditions and optimizing their management may impact outcomes in treating pediatric SDB. [ABSTRACT FROM AUTHOR]

Objective: Sudden sensorineural hearing loss (SSNHL) is a rare presentation requiring timely diagnosis and treatment. Despite recommendations against obtaining computed tomography (CT) imaging of the head in clinical practice guidelines, this investigation is often completed in patients with sudden hearing loss. The aim of this study was to determine the proportion of patients undergoing CT imaging of the head for SSNHL at our center and identify predictive factors for the use of CT imaging. Methods: Retrospective chart review of adult patients referred for SSNHL to two academic otology/neurotology practices between January 2018 and May 2021. Patient demographics, comorbid medical conditions, associated symptoms, location of initial presentation, audiologic results, and completed imaging studies were collected. Statistical analysis was performed with SPSS software. Results: Ninety‐eight patients with audiologically confirmed SSNHL were included. Twenty‐two patients (22.4%) underwent CT imaging as an investigation for SSNHL. The presence of vertigo (odds ratio 6.90; 95% confidence interval 2.43, 19.56) and presentation to the emergency room (odds ratio 8.71; 95% confidence interval 3.02, 25.16) were significantly associated with undergoing CT imaging. These two variables were statistically significant independent predictors of CT imaging on multivariate regression analysis (p =.01, p =.001, respectively). Conclusion: A significant proportion of patients with SSNHL undergo low‐yield CT imaging of the head, particularly patients presenting to the emergency room with vertigo. These results highlight an opportunity for focused education and quality improvement initiatives. Level of evidence: 4. [ABSTRACT FROM AUTHOR]