TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer.

A subgroup of breast cancers has several metabolic compartments. The mechanisms by which metabolic compartmentalization develop in tumors are poorly characterized. TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. Hence we set out to determine the effects of TIGAR expression on breast carcinoma and fibroblast glycolytic phenotype and tumor growth. The overexpression of this bisphosphatase in carcinoma cells induces expression of enzymes and transporters involved in the catabolism of lactate and glutamine. Carcinoma cells overexpressing TIGAR have higher oxygen consumption rates and ATP levels when exposed to glutamine, lactate, or the combination of glutamine and lactate. Coculture of TIGAR overexpressing carcinoma cells and fibroblasts compared with control cocultures induce more pronounced glycolytic differences between carcinoma and fibroblast cells. Carcinoma cells overexpressing TIGAR have reduced glucose uptake and lactate production. Conversely, fibroblasts in coculture with TIGAR overexpressing carcinoma cells induce HIF (hypoxia-inducible factor) activation with increased glucose uptake, increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and lactate dehydrogenase-A expression. We also studied the effect of this enzyme on tumor growth. TIGAR overexpression in carcinoma cells increases tumor growth in vivo with increased proliferation rates. However, a catalytically inactive variant of TIGAR did not induce tumor growth. Therefore, TIGAR expression in breast carcinoma cells promotes metabolic compartmentalization and tumor growth with a mitochondrial metabolic phenotype with lactate and glutamine catabolism. Targeting TIGAR warrants consideration as a potential therapy for breast cancer

Endoscopic outcomes in patients with AERD treated with topical antibiotics and intranasal corticosteroids

Background: Identifying effective therapy for recalcitrant chronic rhinosinusitis with nasal polyposis (CRSwNP) is a major challenge; and subtypes such as aspirin-exacerbated respiratory disease (AERD) are even more difficult to treat. Evidence on topical antibiotics use in (CRSwNP) is lacking. Current consensus guidelines recommend against its routine use, but recent reviews show some benefit when managing recalcitrant disease after endoscopic sinus surgery (ESS). Objective: Evaluate the effect of culture-directed topical antibiotics on sinonasal outcomes in AERD patients with a positive perioperative sinonasal bacterial culture who have undergone ESS. Methods: A retrospective cohort study of AERD patients with positive sinonasal culture, who underwent ESS from 2016 to 2021 was performed. Forty-four patients were identified and stratified based on their postoperative medical treatment. Twenty-six underwent postoperative intranasal corticosteroids (INCS) alone, while eighteen underwent INCS plus a 4-weeks treatment with topical antibiotics. SNOT-22 and Lund-Kennedy score (LKS) were assessed preoperatively and at 4-weeks and 4-6 months after ESS. Results: A statistically significant improvement in the 4-weeks and 4-6 months postoperative SNOT-22 and LKS were noted within both groups (p(p=0.01). Our linear regression model demonstrated a relationship between the use of combined therapy with INCS and topical antibiotics and the LKS 4-weeks post ESS (p=0.015). Conclusion: In AERD patients with a confirmed sinus infection, the combination of culture-directed topical antibiotics and intranasal corticosteroid irrigations in the postoperative period can provide a short-term improvement in endoscopic scores

The American Preparedness Project: Where the US Public Stands in 2015

The American Preparedness Project was launched by the National Center for Disaster Preparedness (NCDP) in 2002, in the aftermath of the 9/11 attacks in order to survey public perceptions and opinions on disaster preparedness and to acknowledge that a comprehensive understanding of the concerns of individuals and families is critical to emergency planning efforts on all levels. Characterizing such trends is critical because in order to develop effective disaster plans, as well as a sustainable long term disaster preparedness strategy, people need to be confident in (a) the reliability of information from official sources, (b) the capacity of government to perform effectively in a crisis and (c) the capability of response systems, particularly health systems and first responders.The major findings of the 2015 American Preparedness Project are presented in the Key Findings section of this report. The American Preparedness Project survey has been administered eight times since the launch of the project in 2002. Although the content of the questionnaire has changed over time to reflect the changing disaster landscape, a select set of questions has been asked in every iteration of the survey in order to capture changes over time.These questions are presented in the National Trends Since 9/11 section of this report and capture national confidence in household and community preparedness, response systems, and leadership. Following the overview of national trends over time, the report highlights findings from the current survey (see Key Findings in 2015) across the domains of General Preparedness, Natural Disasters and Climate Change,Terrorism, and Children in Disasters. The report concludes with Recommendations for improving national, community and household-level preparedness

Children in Disasters: Do Americans Feel Prepared? A National Survey

This study was led by the National Center for Disaster Preparedness (NCDP) at Columbia University’s Earth Institute on behalf of the Resilient Children/Resilient Communities (RCRC) Initiative, in partnership with Save the Children with funding from GSK.The purpose of the study was to learn more about people’s opinions and attitudes toward disaster preparedness with a focus on children in disasters.The national survey of American households was conducted in December 2015. Eligible participants were 18 years of age or older, and included participants, with or without children, in their household. Many of the families surveyed had children in a K-12 school or in daycare

Advanced cotton fibers exhibit efficient photocatalytic self-cleaning and antimicrobial activity

Functional cotton fibers have a wide range of applications in domestic, commercial, and military settings, and so enhancing the properties of these materials can yield substantial benefits. Herein, we report the creation of functional fibers that are self-cleaning, anti-microbial, and protective against UV radiation. A uniform, and high surface area films of TiO2 were deposited on cotton fibers and gold/silver nanoparticles were directly incorporated on the nanostructured TiO2 surface. The synthetic method is simple and the produced TiO2 film is homogenous and the nanoparticles were shown to be effectively distributed on the surface using a simple photocatalytic reduction method. The Ag/Au-TiO2 coated fibers was morphologically characterized using atomic force microscopy (AFM) and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS), and the self-cleaning properties of noble metal nanoparticle/TiO2 coated fibers were demonstrated by repeated staining followed by exposure to simulated solar light. The 1 mM Ag-TiO2 coated fabric was observed to have the largest improvement in rate of stain extinction compared to the untreated fibers with a methylene blue stain, and the 1 mM Au-TiO2 coated fibers were observed to have the largest improvement versus untreated fibers when stained with Congo red. The fibers maintained consistent photocatalytic activity over multiple cycles, and the resistance of the Ag/Au-TiO2 coated cotton to degradation was verified using Fourier transform infrared spectroscopy (FTIR). An efficient anti-microbial activity of the fibers was confirmed by exposure of the fibers to bacterial culture (Escherichia Coli) and direct observation of antimicrobial activity

Comparing Adult Cannabis Treatment-Seekers Enrolled in a Clinical Trial with National Samples of Cannabis Users in the United States

Background—Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment Episodes Data Set – Admissions. Methods—Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results—Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. Conclusions—These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings

Abuse and Diversion of Buprenorphine Sublingual Tablets and Film

Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants\u27 Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ( unique recipients of a dispensed drug, URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned

TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer

A subgroup of breast cancers has several metabolic compartments. The mechanisms by which metabolic compartmentalization develop in tumors are poorly characterized. TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. Hence we set out to determine the effects of TIGAR expression on breast carcinoma and fibroblast glycolytic phenotype and tumor growth. The overexpression of this bisphosphatase in carcinoma cells induces expression of enzymes and transporters involved in the catabolism of lactate and glutamine. Carcinoma cells overexpressing TIGAR have higher oxygen consumption rates and ATP levels when exposed to glutamine, lactate, or the combination of glutamine and lactate. Coculture of TIGAR overexpressing carcinoma cells and fibroblasts compared with control cocultures induce more pronounced glycolytic differences between carcinoma and fibroblast cells. Carcinoma cells overexpressing TIGAR have reduced glucose uptake and lactate production. Conversely, fibroblasts in coculture with TIGAR overexpressing carcinoma cells induce HIF (hypoxia-inducible factor) activation with increased glucose uptake, increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and lactate dehydrogenase-A expression. We also studied the effect of this enzyme on tumor growth. TIGAR overexpression in carcinoma cells increases tumor growth in vivo with increased proliferation rates. However, a catalytically inactive variant of TIGAR did not induce tumor growth. Therefore, TIGAR expression in breast carcinoma cells promotes metabolic compartmentalization and tumor growth with a mitochondrial metabolic phenotype with lactate and glutamine catabolism. Targeting TIGAR warrants consideration as a potential therapy for breast cancer

The Fifth Data Release of the Sloan Digital Sky Survey

This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and represents the completion of the SDSS-I project (whose successor, SDSS-II will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 square degrees, and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 square degrees of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS Sixth Data Release (DR6) is now public, available from http://www.sdss.or