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Traffic-related air pollution has been associated with various health risks for human populations living near roadways. Understanding the relationship between traffic density and dispersion of vehicle-released air pollutants is important for assessing human exposure to near-road air pollutants. We performed a literature survey targeting publications containing measurement data of traffic-related air pollutants near roads with distance information on their concentration distribution. Concentration decay rates over down-wind distance away from major roads were calculated for black carbon (BC), carbon monoxide (CO) and nitrogen oxides (NO2 or NOx) and meta-data analysis on these rates was performed. These analyses showed metadata-based exponential decay rates of 0.0026, 0.0019, 0.0004, and 0.0027 m−1 for BC, CO, NO2 and NOx, respectively. Using these measurement data-based decay rates, concentrations for BC, CO, NO2 and NOx over various near-road distances were predicted. These results are useful for enhancing exposure modeling and thus more reliably assessing the health risk of exposure to near road air pollution.

© The Author 2014.Aims Although active-controlled trials with renin-angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compa

ABSTRACT To examine factors influencing long-term ozone ([O.sub.3]) exposures by children living in urban communities, the authors analyzed longitudinal data on personal, indoor, and outdoor [O.sub.3] concentrations, as well as [...]

Research has been conducted on different neisserial genomes. The distinction between Neisseria meningitidis and N. gonorrhoeae has been investigated in the effort to understand the differential pathogenesis of these related but distinct pathogens, and the results are described.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can cause significant physical, mental, and socioeconomic burden. There remains a paucity of literature on HSin the pediatric population. This systematic review highlights recent advances in pediatric HS in epidemiology, presentation, comorbidities, and management. PubMed, Embase, Google Scholar, and Clinicaltrials.gov databases were used to identify trials and articles published on HS in pediatric patients between January 2015 and October 2019. A total of 39 articles were included. Current evidence suggests that pediatric onset HS may be associated with genetic factors along with endocrine and metabolic abnormalities. Delayed diagnosis in children with HS contributes to poor outcomes. Overall, children and adults with HS share similar lesion types and involved areas. Pediatric HS is associated with a number of comorbid conditions including acne, obesity, inflammatory joint disease, Down syndrome, inflammatory bowel disease, and diabetes. There are currently no pediatric treatment guidelines. Adalimumab is approved for the treatment of moderate-to-severe HS in children 12 and older. Other targeted immunomodulators and hormonal modulators are under investigation. Although the number of studies concerning HS are increasing, further investigation is warranted to better characterize HS, facilitate early diagnosis, and determine the best management for children. [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated. Objectives: This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march. Methods: A literature search was conducted using the PubMed database for relevant articles with the keywords ‘atopic dermatitis’, ‘epithelial barrier’, ‘skin’, ‘gut’, ‘lung’, ‘microbiome’ and ‘immune dysregulation’. Results: Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin‐mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract. Conclusions: As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long‐term outcomes and reduce allergen sensitization in the airway and gut. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Tiffany Y Loh,1 Jennifer L Hsiao,2 Vivian Y Shi1 1University of Arizona, Division of Dermatology, Tucson, AZ, USA; 2University of California Los Angeles, Division of Dermatology, Los Angeles, CA, USACorrespondence: Vivian Y ShiDivision of Dermatology, University of Arizona, 7165 N Pima Canyon Drive, Tucson, AZ 85718, USATel +1 520 694 2055Fax +1 520 694 2005Email vshi@email.arizona.eduBackground: Atopic dermatitis (AD) is a chronic, relapsing skin condition with a wide disease spectrum. Moderate-to-severe cases often need systemic treatment. Conventional immunosuppressants have extensive side effect profiles and require close monitoring. In recent decades, there has been increasing interest in developing targeted systemic immunomodulators for AD, as they have been shown to have efficacy for AD as well as favorable safety profiles. Herein, we review the recent data on lebrikizumab, an interleukin (IL)-13 inhibitor, and its potential role in the treatment of AD.Objective: Review the mechanism of action, and available data on the efficacy and safety of lebrikizumab for the treatment of AD.Methods: PubMed, Google Scholar, and clinicaltrials.gov searches were performed with the following terms: “atopic dermatitis,” “dermatitis,” “eczema,” “lebrikizumab,” “IL-4,” and “IL-13.”Results: Two Phase II randomized controlled clinical trials have been conducted to evaluate the use of lebrikizumab in a total of 289 patients with moderate-severe AD and inadequate response to topical corticosteroids. Patients treated with lebrikizumab experienced significantly more improvement in their AD compared to placebo, as measured by Eczema Area and Severity Index (EASI)-50 and EASI-75 scores, pruritus scores, and reduction in body surface area (BSA). Its clinical efficacy appears to be dose-dependent, and it has a favorable side effect profile and is generally well tolerated.Conclusion: Lebrikizumab appears to be a promising emerging targeted biologic for the treatment of moderate-to-severe AD. Further Phase III studies investigating optimal dosing regimens and safety profile are needed.Keywords: lebrikizumab, atopic dermatitis, eczema, dermatitis, IL-4, IL-13

Purpose/objective(s): Patients with recurrence of cervical cancer after definitive radiation therapy (RT) have < 5% long-term survival. Early detection of asymptomatic recurrence may provide an opportunity for salvage. Serum squamous cell carcinoma antigen (SCCA) is an effective biomarker for response to RT and overall prognosis. Retrospective studies indicate that elevated serum SCCA in the post-RT surveillance setting may also be useful to detect asymptomatic recurrence. We hypothesized that elevated serum SCCA at follow-up is a specific indicator of recurrence after definitive RT.Materials/methods: Serum SCCA (fuSCCA) values measured during the surveillance of patients treated with definitive-intent RT from 2007-2019 were retrospectively analyzed. Serum SCCA was measured by ELISA in a CLIA-certified lab (normal range 0.0-2.2 ng/mL), and was recorded along with patient and tumor factors. Follow-up consisted of history, physical examination, serum SCCA, and imaging when indicated. Recurrence was confirmed pathologically when possible. FuSCCA was defined as the last available value, or as the value closest to the date of recurrence (no more than 6 months prior and 3 weeks after). Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of fuSCCA was determined for recurrence. Analysis was performed for the whole cohort and for a subgroup of patients with available pretreatment SCCA values. Difference in fuSCCA between patients with and without recurrence was compared using a Student's t-test.Results: 258 patients were identified with any follow-up SCCA value, 227 with fuSCCA as defined above. Mean age at diagnosis of the whole cohort was 52.7 years. FIGO stage was IB in 19.8%, IIB in 22.9%, IIIC1 in 39.1%, and IIIC2 in 13.2% of patients. After a median of follow-up 50.4 months (range 1.4 - 147.7), 67.1% of patients had no evidence of disease, 6.2% were alive with disease, 21.7% had died of cervical cancer, and 5.0% had died of intercurrent disease. Mean fuSCCA was 0.9 ng/mL (range 0-26.6) for 175 patients with no recurrence and 6.0 ng/mL (range 0-97) for 52 patients with recurrence (two-tailed P = 0.02). Se, Sp, PPV, and NPV of last fuSCCA for recurrence all patients and those with elevated pretreatment serum SCCA is shown in Table 1. Of 81 patients with normal pre-treatment SCCA only two had an elevated value at any point during surveillance, one of whom experienced recurrence.Conclusion: For patients with elevated pre-treatment serum SCCA, surveillance serum SCCA is an inexpensive and accessible test with high specificity and negative predictive value for recurrence. Surveillance of serum SCCA is of limited utility in patients with normal pre-treatment values. [ABSTRACT FROM AUTHOR]

Author(s): Shi V. Liu [1] Sir I could not agree more with the author of your Opinion 'Resolution to enhance confident creativity' (Nature 403, 1; 2000) that 'there will always [...]

Magnetite is a common product of bacterial iron reduction and may serve as a potential physical indicator of biological activity in geological settings. Here we report the formation of single-domain magnetite under laboratory conditions by a thermophilic fermentative bacterial strain TOR-39 that was isolated from the deep subsurface. Time-course analyses were performed at 65 [degrees] C to study the effect of bacterial activity on solution chemistry and magnetite formation during the growth of TOR-39. Run products were examined by transmission electron microscopy. Magnetite particles formed exclusively outside of bacterial cells and exhibited octahedral shapes having relatively equal length and width (

Introduction. Glioblastomas multiformes (GBM) remain incurable in most cases. Their invasion into normal brain makes current therapies ineffective. Post-mortem studies suggest about a 25% of GBMs invade less than 1 cm from the tumour bulk and 20% invade more than 3 cm. Aim of study. The study aims to use DTI to assess tumour extension and determine how previously reported patterns relate to the progression-free survival (PFS). Materials and methods. Twenty-five patients with GBM treated according to the EORTC/NCIC protocol were retrospectively analysed. Patients were imaged post-operatively at 1.5 T. The sequences were composed of standard anatomical and a standard DTI sequence. As described earlier p and q maps were constructed. For each of the p and q maps, regions of interest were drawn around the visible abnormality. Patients were assigned a diffuse, localised or minimally invasive pattern. Progression was defined according to the RANO criteria4 and PFS determined in days. Kaplan-Meier plots of survival for the three groups were plotted as were the proportion of patients who had not progressed at 24 months. Results. The median PFS for the diffuse group was 278 days, for the localised group 605 days and 820 days for the minimally invasive group. Three-fourth of the minimally invasive group were progression-free at 24 months (LOG RANK 9.25; p = 0.010). Conclusion. It is possible to identify three invasive phenotypes in GBMs using Diffusion tensor imaging , and these three phenotypes have different progression free survival. A minimal phenotype (20% of patients) predicts a greater delay to progression. [ABSTRACT FROM AUTHOR]

The article features the CHAD Explorer, a web application which can be used to explore time-activity stored in the Consolidated Human Activity Database (CHAD) developed by the U.S. Environmental Protection Agency (EPA).

Background: Dietary exposure from food to toxic inorganic arsenic (iAs) in the general U.S. population has not been well studied. Objectives: The goal of this research was to quantify dietary As exposure and analyze the major contributors to total As (tAs) and iAs. Another objective was to compare model predictions with observed data. Method s: Probabilistic exposure modeling for dietary As was conducted with the Stochastic Human Exposure and Dose Simulation-Dietary (SHEDS-Dietary) model, based on data from the National Health and Nutrition Examination Survey. The dose modeling was conducted by combining the SHEDS-Dietary model with the MENTOR-3P (Modeling ENvironment for TOtal Risk with Physiologically Based Pharmacokinetic Modeling for Populations) system. Model evaluation was conducted via comparing exposure and dose-modeling predictions against duplicate diet data and biomarker measurements, respectively, for the same individuals. Results: The mean modeled tAs exposure from food is 0.38 μg/kg/day, which is approximately 14 times higher than the mean As exposures from the drinking water. The mean iAs exposure from food is 0.05 μg/kg/day (1.96 μg/day), which is approximately two times higher than the mean iAs exposures from the drinking water. The modeled exposure and dose estimates matched well with the duplicate diet data and measured As biomarkers. The major food contributors to iAs exposure were the following: vegetables (24%); fruit juices and fruits (18%); rice (17%); beer and wine (12%); and flour, corn, and wheat (11%). Approximately 10% of tAs exposure from foods is the toxic iAs form. Conclusions: The general U.S. population may be exposed to tAs and iAs more from eating some foods than from drinking water. In addition, this model evaluation effort provides more confidence in the exposure assessment tools used. [ABSTRACT FROM AUTHOR]

Over the past 20 months, reports claiming the generation of induced pluripotent stem (iPS) cells with characteristics identical to those of embryonic stem (ES) cells from nonembryonic tissue have captured great attention in both the scientific community and the general public. In the light of the continuing controversy over the use of ES cells, these reports have profound ramifications. This review calls into question the validity of many claims made in these reports—claims that have led to the rapid and premature acceptance of using iPS cells as a viable alternative to using normal stem cells for regenerative therapy. How convincing is the evidence supporting the various claims made for the iPS cells Are there other more plausible explanations for the same observations What are these iPS cells Are they really safe for therapeutic use Should the iPS technique be considered, in the absence of any direct evidence for inductionand reprogramming, as a realistic alternative for somatic cell nuclear transfer (SCNT) to generateES-like cells This review attempts to encourage reflections on and offer alternative views for key aspects of iPS cells and studies. [ABSTRACT FROM AUTHOR]

Background: Occurrence of tumors at multiple sites is a hallmark of malignant cancers and contributes to the high mortality of cancers. The formation of multi-site cancers (MSCs) has conventionally been regarded as a result of hematogenous metastasis. However, some MSCs may appear as unusual in the sense of vascular dissemination pattern and therefore be explained by alternative metastasis models or even by non-metastatic independent formation mechanisms. Results: Through literature review and incorporation of recent advance in understanding aging and development, we identified two alternative mechanisms for the independent formation of MSCs: 1) formation of separate tumors from cancer-initiating cells (CICs) mutated at an early stage of development and then diverging as to their physical locations upon further development, 2) formation of separate tumors from different CICs that contain mutations in some convergent ways. Either of these processes does not require long-distance migration and/or vascular dissemination of cancer cells from a primary site to a secondary site. Thus, we classify the formation of these MSCs from indigenous CICs (iCICs) into a new mechanistic category of tumor formation -- multigenesis. Conclusion: A multigenesis view on multi-site cancer (MSCs) may offer explanations for some "unusual metastasis" and has important implications for designing expanded strategies for the diagnosis and treatment of cancers. [ABSTRACT FROM AUTHOR]

To examine factors influencing long-term ozone (O3) exposures by children living in urban communities, the authors analyzed longitudinal data on personal, indoor, and outdoor O3 concentrations, as well as related housing and other questionnaire information collected in the one-year- long Harvard Southern California Chronic Ozone Exposure Study. Of 224 children contained in the original data set, 160 children were found to have longitudinal measurements of O3 concentrations in at least six months of 12 months of the study period. Data for these children were randomly split into two equal sets: one for model development and the other for model validation. Mixed models with various variance-covariance structures were developed to evaluate statistically important predictors for chronic personal ozone exposures. Model predictions were then validated against the field measurements using an empirical best-linear unbiased prediction technique. The results of model fitting showed that the most important predictors for personal ozone exposure include indoor O3 concentration, central ambient O3 concentration, outdoor O3 concentration, season, gender, outdoor time, house fan usage, and the presence of a gas range in the house. Hierarchical models of personal O3 concentrations indicate the following levels of explanatory power for each of the predictive models: indoor and outdoor O3 concentrations plus questionnaire variables, central and indoor O3 concentrations plus questionnaire variables, indoor O3 concentrations plus questionnaire variables, central O3 concentrations plus questionnaire variables, and questionnaire data alone on time activity and housing characteristics. These results provide important information on key predictors of chronic human exposures to ambient O3 for children and offer insights into how to reliably and cost-effectively predict personal O3 exposures in the future. Furthermore, the techniques and findings derived from this study also have strong implications for selecting the most reliable and cost-effective exposure study design and modeling approaches for other ambient pollutants, such as fine particulate matter and selected urban air toxics. [ABSTRACT FROM AUTHOR]

Discusses the isolation and characterization of metal-reducing Thermoanaerobacter ethanolicus strains from samples taken from the Piceance Basin in Colorado. Results of the molecular analyses of bacterial isolates; Physiological characteristics of isolates; Mineralogical characteristics.

Linked Article: Howells et al. Br J Dermatol 2021; 185:921–934. [ABSTRACT FROM AUTHOR]

Khiem A Tran,1,* Michelle Y Cheng,1,* Anupam Mitra,1 Hiromi Ogawa,1 Vivian Y Shi,1 Laura P Olney,1 April M Kloxin,2 Emanual Maverakis1 1Department of Dermatology, University of California, Davis, Sacramento, CA, USA; 2Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA *These authors contributed equally to this work Abstract: The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy. Keywords: cobimetinib, trametinib, vemurafenib, dabrafenib, BRAF inhibitor, MAPK pathway