Factors that support Indigenous involvement in multi-actor environmental stewardship

Regional, multi-actor environmental collaborations bring together diverse parties to achieve environmental protection and stewardship outcomes. Involving a range of participants helps involve alternative forms of knowledge, expertise, and perspectives; it may also present greater challenges in reaching agreements, particularly when both Indigenous and non-Indigenous parties are involved. The authors conduct a cross-case study of 39 regional partnerships involving Indigenous nations from the Great Lakes basin of North America with the aim of determining the factors that enable Indigenous partners to remain engaged in multi-actor collaborations. Six characteristics influenced Indigenous nations’ willingness to remain engaged: respect for Indigenous knowledges, control of knowledge mobilization, intergenerational involvement, self-determination, continuous cross-cultural education, and early involvement. Being attentive of these factors can help partnerships achieve their environmental goals by keeping important partners at the table

Population PK modelling and simulation based on fluoxetine and norfluoxetine concentrations in milk: a milk concentration-based prediction model

AIMS: Population pharmacokinetic (pop PK) modelling can be used for PK assessment of drugs in breast milk. However, complex mechanistic modelling of a parent and an active metabolite using both blood and milk samples is challenging. We aimed to develop a simple predictive pop PK model for milk concentration-time profiles of a parent and a metabolite, using data on fluoxetine (FX) and its active metabolite, norfluoxetine (NFX), in milk

Assessing the effect of mercury pollution on cultured benthic foraminifera community using morphological and eDNA metabarcoding approaches

none14sìMercury (Hg) is a highly toxic element for living organisms and is known to bioaccumulate and biomagnify. Here, we analyze the response of benthic foraminifera communities cultured in mesocosm and exposed to different concentrations of Hg. Standard morphological analyses and environmental DNA metabarcoding show evidence that Hg pollution has detrimental effects on benthic foraminifera. The molecular analysis provides a more complete view of foraminiferal communities including the soft-walled single-chambered monothalamiids and small-sized hard-shelled rotaliids and textulariids than the morphological one. Among these taxa that are typically overlooked in morphological studies we found potential bioindicators of Hg pollution. The mesocosm approach proves to be an effective method to study benthic foraminiferal responses to various types and concentrations of pollutants over time. This study further supports foraminiferal metabarcoding as a complementary and/or alternative method to standard biomonitoring program based on the morphological identification of species communities.openFrontalini, Fabrizio; Greco, Mattia; Di Bella, Letizia; Lejzerowicz, Franck; Reo, Emanuela; Caruso, Antonio; Cosentino, Claudia; Maccotta, Antonella; Scopelliti, Giovanna; Nardelli, Maria Pia; Losada, Maria Teresa; Armynot du Châtelet, Eric; Coccioni, Rodolfo; Pawlowski, JanFrontalini, Fabrizio; Greco, Mattia; Di Bella, Letizia; Lejzerowicz, Franck; Reo, Emanuela; Caruso, Antonio; Cosentino, Claudia; Maccotta, Antonella; Scopelliti, Giovanna; Nardelli, Maria Pia; Losada, Maria Teresa; Armynot du Châtelet, Eric; Coccioni, Rodolfo; Pawlowski, Ja

Embolic stroke complicating Staphylococcus aureus endocarditis circumstantially linked to rectal trauma from foreign body: a first case report

BACKGROUND: Diagnostic and therapeutic instrumentation of the lower gastrointestinal tract has been reported to result in bacteremia and endocarditis. No such case has been reported in persons with a history of rectal foreign body insertion despite its potential for greater trauma. CASE PRESENTATION: A 58-year-old male was admitted with confusion and inability to speak. His past history was notable for hospitalization to extract a retained plastic soda bottle from the rectosigmoid two years prior. On examination, he was febrile, tachycardic and hypotensive. There was an apical pansystolic murmur on cardiac examination. He had a mixed receptive and expressive aphasia, and a right hemiparesis. On rectal examination he had perianal erythema and diminished sphincter tone. Magnetic resonance imaging of the brain showed infarction of the occipital and frontal lobes. Transesophageal Echocardiography of the heart revealed vegetations on the mitral valve. All of his blood culture bottles grew methicillin sensitive Staphylococcus aureus. He was successfully treated for bacterial endocarditis with intravenous nafcillin and gentamicin. The rectum is frequently colonized by Staphylococcus aureus and trauma to its mucosa can lead to bacteremia and endocarditis with this organism. In the absence of corroborative evidence such as presented here, it is difficult to make a correlation between staphylococcal endocarditis and anorectal foreign body insertion due to patients being less than forthcoming CONCLUSION: There is a potential risk of staphylococcal bacteremia and endocarditis with rectal foreign body insertion. Further studies are needed to explore this finding. Detailed sexual history and patient counseling should be made a part of routine primary care

Comparative Study on the Inhibitory Effects of α-Tocopherol and Radon on Carbon Tetrachloride-Induced Renal Damage

Since the 2011 nuclear accident in Fukushima, the effects of low-dose irradiation, especially internal exposure, are at the forefront of everyone’s attention. However, low-dose radiation induced various stimulating effects such as activation of antioxidative and immune functions. In this study, we attempted to evaluate the quantitative effects of the activation of antioxidative activities in kidney induced by radon inhalation on carbon tetrachloride (CCl4)-induced renal damage. Mice were subjected to intraperitoneal (i.p.) injection of CCl4 after inhaling approximately 1000 or 2000 Bq/m3 radon for 24 h, or immediately after i.p. injection of α-tocopherol (100, 300, or 500 mg/kg bodyweight). In case of renal function, radon inhalation at a concentration of 2000 Bq/m3 has the inhibitory effects similar to α-tocopherol treatment at a dose of 300–500 mg/kg bodyweight. The activities of superoxide dismutase and catalase in kidneys were significantly higher in mice exposed to radon as compared to mice treated with CCl4 alone. These findings suggest that radon inhalation has an antioxidative effect against CCl4-induced renal damage similar to the antioxidative effects of α-tocopherol due to induction of antioxidative functions

Prospective Study of Infection, Colonization and Carriage of Methicillin-Resistant Staphylococcus Aureus in an Outbreak Affecting 990 Patients

In the three years between November 1989 and October 1992, an outbreak of methicillin-resistantStaphylococcus aureus (MRSA) affected 990 patients at a university hospital. The distribution of patients with carriage, colonization or infection was investigated prospectively. Nosocomial acquisition was confirmed in at least 928 patients, 525 of whom were identified from clinical specimens as being infected (n=418) or colonized (n=107) by MRSA. An additional 403 patients were identified from screening specimens, of whom 58 subsequently became infected and 18 colonized. Screening of the nose, throat and perineum detected 98 % of all carriers. Of the 580 infections in 476 patients, surgical wound, urinary tract and skin infections accounted for 58 % of the infections. Of the 476 infected patients, death was attributable to MRSA infection in 13 %. Colonization with MRSA was found in 127 patients and 42 % of 165 colonized sites were the skin. Auto-infection from nasal carriage or cross-infection, probably via staff hands, seemed to be the most common mode of acquisition of MRSA infections

Epigenetic Regulation of Cell Type–Specific Expression Patterns in the Human Mammary Epithelium

Differentiation is an epigenetic program that involves the gradual loss of pluripotency and acquisition of cell type–specific features. Understanding these processes requires genome-wide analysis of epigenetic and gene expression profiles, which have been challenging in primary tissue samples due to limited numbers of cells available. Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, as well as gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type–specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation

A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of <it>KRAS </it>are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells.</p> <p>Methods</p> <p>DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for <it>KRAS </it>amplification by quantitative PCR, and investigated <it>KRAS </it>amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of <it>KRAS </it>knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively.</p> <p>Results</p> <p>DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the <it>KRAS </it>gene locus. Amplification of the <it>KRAS </it>locus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification). <it>KRAS </it>mutations were identified in two of the three cell lines in which <it>KRAS </it>was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased <it>KRAS </it>copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type <it>KRAS</it>, but not in cells with amplified mutant <it>KRAS</it>. Knock-down of <it>KRAS </it>in gastric cancer cells that carried amplified wild-type <it>KRAS </it>resulted in the inhibition of cell growth and suppression of p44/42 MAP kinase and AKT activity.</p> <p>Conclusion</p> <p>Our study highlights the utility of DGS for identification of copy-number alterations. Using DGS, we identified <it>KRAS </it>as a gene that is amplified in human gastric cancer. We demonstrated that gene amplification likely forms the molecular basis of overactivation of KRAS in gastric cancer. Additional studies using a larger cohort of gastric cancer specimens are required to determine the diagnostic and therapeutic implications of <it>KRAS </it>amplification and overexpression.</p

Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles

Saliva is a readily accessible and informative biofluid, making it ideal for the early detection of a wide range of diseases including cardiovascular, renal, and autoimmune diseases, viral and bacterial infections and, importantly, cancers. Saliva-based diagnostics, particularly those based on metabolomics technology, are emerging and offer a promising clinical strategy, characterizing the association between salivary analytes and a particular disease. Here, we conducted a comprehensive metabolite analysis of saliva samples obtained from 215 individuals (69 oral, 18 pancreatic and 30 breast cancer patients, 11 periodontal disease patients and 87 healthy controls) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We identified 57 principal metabolites that can be used to accurately predict the probability of being affected by each individual disease. Although small but significant correlations were found between the known patient characteristics and the quantified metabolites, the profiles manifested relatively higher concentrations of most of the metabolites detected in all three cancers in comparison with those in people with periodontal disease and control subjects. This suggests that cancer-specific signatures are embedded in saliva metabolites. Multiple logistic regression models yielded high area under the receiver-operating characteristic curves (AUCs) to discriminate healthy controls from each disease. The AUCs were 0.865 for oral cancer, 0.973 for breast cancer, 0.993 for pancreatic cancer, and 0.969 for periodontal diseases. The accuracy of the models was also high, with cross-validation AUCs of 0.810, 0.881, 0.994, and 0.954, respectively. Quantitative information for these 57 metabolites and their combinations enable us to predict disease susceptibility. These metabolites are promising biomarkers for medical screening

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p