Trace levels of sewage effluent are sufficient to increase class 1 integron prevalence in freshwater biofilms without changing the core community

Most river systems are impacted by sewage effluent. It remains unclear if there is a lower threshold to the concentration of sewage effluent that can significantly change the structure of the microbial community and its mobile genetic elements in a natural river biofilm. We used novel in situ mesocosms to conduct replicated experiments to study how the addition of low-level concentrations of sewage effluent (nominally 2.5 ppm) affects river biofilms in two contrasting Chalk river systems, the Rivers Kennet and Lambourn (high/low sewage impact, respectively). 16S sequencing and qPCR showed that community composition was not significantly changed by the sewage effluent addition, but class 1 integron prevalence (Lambourn control 0.07% (SE ± 0.01), Lambourn sewage effluent 0.11% (SE ± 0.006), Kennet control 0.56% (SE ± 0.01), Kennet sewage effluent 1.28% (SE ± 0.16)) was significantly greater in the communities exposed to sewage effluent than in the control flumes (ANOVA, F = 5.11, p = 0.045) in both rivers. Furthermore, the difference in integron prevalence between the Kennet control (no sewage effluent addition) and Kennet sewage-treated samples was proportionally greater than the difference in prevalence between the Lambourn control and sewage-treated samples (ANOVA (interaction between treatment and river), F = 6.42, p = 0.028). Mechanisms that lead to such differences could include macronutrient/biofilm or phage/bacteria interactions. Our findings highlight the role that low-level exposure to complex polluting mixtures such as sewage effluent can play in the spread of antibiotic resistance genes. The results also highlight that certain conditions, such as macronutrient load, might accelerate spread of antibiotic resistance genes

Morphological and functional evaluation of an animal model for the retinal degeneration induced by N-methyl-N-nitrosourea

The retinal degeneration (RD) is a general cause of blindness. To study its pathophysiology and evaluate the effects of new therapeutic agents before clinical trials, it is essential to establish reliable and stable animal models. This study evaluated a RD animal model in which blindness was induced by N-methyl-N-nitrosourea (MNU), a potent retinotoxin leading to apoptosis of photoreceptors. MNU was applied to the Sprague-Dawley rats by a single intraperitoneal injection in different doses (40, 50, and 60 mg/kg). The retinal functions were examined at 1 week after MNU injection by electroretinogram (ERG). Afterwards, each retina was examined by hematoxylin and eosin stain and immunohistochemistry with anti-glial fibrillary acidic protein antibody. Upon MNU injection of 40, 50 and 60 mg/kg, the ERG amplitude of a-waves showed significant reductions of 7, 26, and 44%, respectively, when compared to that of normal a-waves. The b-wave amplitudes were about 89, 65, and 58% of normal b-waves in the response to scotopic light stimulus. At 1 week, 2 weeks, and 4 weeks after MNU injection (50 mg/kg), all scotopic ERG components decreased progressively. In addition, degeneration of retinal neurons was observed in a time- and dose-dependent manner after MNU injection. Taken together, functional reduction following RD induced by MNU correlates with morphological changes. Thus, this RD rat model may be a useful model to study its pathophysiology and to evaluate the effects of new therapeutic agents before clinical trials

Reflections Magazine of the Faculty of Education. Volume 5 No. 6 June 1993

La Revista Reflexiones de la Facultad de Educación de la Universidad Autónoma de Bucaramanga recibe para su publicación trabajos sobre Educación, Infancia, formación de Docentes, Trabajo Comunitario, Psicología Infantil y temas afines.EDITORIAL. -- USOS Y ABUSOS DEL QUINTO CENTENARIO. -- Los basuriegos del carrasco. --- Ciudad norte. -- Fundamentos teóricos a tener en cuenta en el diseño del programa de formación moral. -- La dimensión de las palabras. -- Nuestra universidad¡ hacia dónde?. -- Filosofía personal. --The Reflections Magazine of the Faculty of Education of the Autonomous University of Bucaramanga receives for its publication of works on Education, Childhood, Teacher Training, Community Work, Child Psychology and topics related

Reflections Magazine of the Faculty of Education. Volume 5 No. 6 September 1995

La Universidad Autónoma de Bucaramanga desde 1.992 viene realizando acciones tendientes a la clarificación y definición de políticas y criterios que señalen directrices para la actualización del Proyecto Educativo Institucional a la luz de los nuevos desarrollos sociales, políticos y culturales del país.The Autonomous University of Bucaramanga since 1992 has been carrying out actions aimed at clarifying and defining of policies and criteria that indicate guidelines for updating the Institutional Educational Project in light of the new social, political and cultural developments in the country.Modalidad Presencia

Multicriteria decision analysis for the evaluation of water quality improvement and ecosystem service provision

Water and land management decisions require consideration of multiple factors. Multicriteria decision analysis (MCDA) provides a structured, auditable and transparent tool that helps inform and add rigour to multioption decisions. MCDA was used in a payment for ecosystem services (PES) project to evaluate options for delivering good ecological status in Tortworth Brook, Gloucestershire, UK. Following a process of stakeholder engagement, final options considered were: (1) doing nothing; (2) modifying existing sewage treatment works; (3) a single integrated constructed wetland (ICW) targeting multiple ecosystem service outcomes; and (4) catchment wide multiple ICWs. The analysis concluded that the ‘do nothing’ option and modifying the existing works are both likely to provide poor utility and value for money. Both ICW options offered the greatest utility in terms of optimising the benefits to all stakeholders

The Inflammatory Response After Ischemic Stroke: Targeting β\u3csub\u3e2\u3c/sub\u3e and β\u3csub\u3e1\u3c/sub\u3e Integrins

Ischemic stroke is a leading cause of death and disability with limited therapeutic options. Resulting inflammatory mechanisms after reperfusion (removal of the thrombus) result in cytokine activation, calcium influx, and leukocytic infiltration to the area of ischemia. In particular, leukocytes migrate toward areas of inflammation by use of integrins, particularly integrins β1 and β2. Integrins have been shown to be necessary for leukocyte adhesion and migration, and thus are of immediate interest in many inflammatory diseases, including ischemic stroke. In this review, we identify the main integrins involved in leukocytic migration following stroke (αLβ2, αDβ2, α4β1, and α5β1) and targeted clinical therapeutic interventions

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)