Evaluating the use of 3'-(p-Aminophenyl) fluorescein for determining the formation of highly reactive oxygen species in particle suspensions

<p>Abstract</p> <p>Background</p> <p>Given the importance of highly reactive oxygen species (hROS) as reactants in a wide range of biological, photochemical, and environmental systems there is an interest in detection and quantification of these species. The extreme reactivity of the hROS, which includes hydroxyl radicals, presents an analytical challenge. 3'-(<it>p</it>-Aminophenyl) fluorescein (APF) is a relatively new probe used for measuring hROS. Here, we further evaluate the use of APF as a method for the detection of hydroxyl radicals in particle suspensions.</p> <p>Results</p> <p>Particle-generated hROS can be quantified with an estimated detection limit of 50 nM. Measurements of hROS in two National Institute of Standards and Technology (NIST 2709 and 2710) soil suspensions and a pyrite suspension show non-linear particle dose-response curves for hROS generation. APF can also be used in solutions containing no dissolved molecular oxygen (O₂) to determine the role of O₂in the formation of hROS. Results confirm that O₂is mechanistically important in the formation of hROS by dissolved ferrous iron and in pyrite suspensions.</p> <p>Conclusion</p> <p>Given the non-linear dose-response curves for particle generation of hROS, we recommend using several particle loadings in experiments aimed to compare particles for their hROS generation potential. The method presented here is specific to hROS and simple to perform. The analysis can be conducted in mobile labs as only basic laboratory equipment is required.</p

Frequency of human immunodeficiency virus (HIV) testing in urban vs. rural areas of the United States: Results from a nationally-representative sample

<p>Abstract</p> <p>Background</p> <p>Studies in the United States show that rural persons with HIV are more likely than their urban counterparts to be diagnosed at a late stage of infection, suggesting missed opportunities for HIV testing in rural areas. To inform discussion of HIV testing policies in rural areas, we generated nationally representative, population-based estimates of HIV testing frequencies in urban vs. rural areas of the United States.</p> <p>Methods</p> <p>Secondary analysis of 2005 and 2009 Behavioral Risk Factor Surveillance System (BRFSS) data. Dependent variables were self-reported lifetime and past-year HIV testing. Urban vs. rural residence was determined using the metropolitan area framework and Urban Influence Codes and was categorized as 1) metropolitan, center city (the most urban); 2) metropolitan, other; 3) non-metropolitan, adjacent to metropolitan; 4) non-metropolitan, micropolitan; and 4) remote, non-metropolitan (the most rural).</p> <p>Results</p> <p>The 2005 sample included 257,895 respondents. Lifetime HIV testing frequencies ranged from 43.6% among persons residing in the most urban areas to 32.2% among persons in the most rural areas (P < 0.001). Past-year testing frequencies ranged from 13.5% to 7.3% in these groups (P < 0.001). After adjusting for demographics (age, sex, race/ethnicity, and region of residence) and self-reported HIV risk factors, persons in the most remote rural areas were substantially less likely than persons in the most urban areas to report HIV testing in the past year (odds ratio 0.65, 95% CI 0.57-0.75). Testing rates in urban and rural areas did not change substantively following the 2006 Centers for Disease Control and Prevention recommendation for routine, population-based HIV testing in healthcare settings. In metropolitan (urban) areas, 11.5% (95% CI 11.2-11.8) reported past-year HIV testing in 2005 vs. 11.4% (95% CI 11.1%-11.7%) in 2009 (P = 0.93). In non-metropolitan areas, 8.7% (95% CI 8.2%-9.2%) were tested in 2005 vs. 7.7% (95% CI 7.2%-8.2%) in 2009 (P = 0.03).</p> <p>Conclusions</p> <p>Rural persons are less likely than urban to report prior HIV testing, which may contribute to later HIV diagnosis in rural areas. There is need to consider strategies to increase HIV testing in rural areas.</p

Dogs and humans respond to emotionally competent stimuli by producing different facial actions

The commonality of facial expressions of emotion has been studied in different species since Darwin, with most of the research focusing on closely related primate species. However, it is unclear to what extent there exists common facial expression in species more phylogenetically distant, but sharing a need for common interspecific emotional understanding. Here we used the objective, anatomically-based tools, FACS and DogFACS (Facial Action Coding Systems), to quantify and compare human and domestic dog facial expressions in response to emotionally-competent stimuli associated with different categories of emotional arousal. We sought to answer two questions: Firstly, do dogs display specific discriminatory facial movements in response to different categories of emotional stimuli? Secondly, do dogs display similar facial movements to humans when reacting in emotionally comparable contexts? We found that dogs displayed distinctive facial actions depending on the category of stimuli. However, dogs produced different facial movements to humans in comparable states of emotional arousal. These results refute the commonality of emotional expression across mammals, since dogs do not display human-like facial expressions. Given the unique interspecific relationship between dogs and humans, two highly social but evolutionarily distant species sharing a common environment, these findings give new insight into the origin of emotion expression

Politicians lie, so do I

This research analyzed whether political leaders make people lie via priming experiments. Priming is a non-conscious and implicit memory effect in which exposure to one stimulus affects the response to another stimulus. Following priming theories, we proposed an innovative concept that people who perceive leaders to be dishonest (such as liar) are likely to lie themselves. We designed three experiments to analyze and critically discussed the potential influence of prime effect on lying behavior, through the prime effect of French political leaders (inc. general politicians, presidents and parties). Experiment 1 discovered that participants with non-politician-prime were less likely to lie (compared to politician-prime). Experiment 2A discovered that, compared to Hollande-prime, Sarkozy-prime led to lying behavior both in gravity (i.e. bigger lies) and frequency (i.e. lying more frequently). Experiment 2B discovered that Republicans-prime yielded an impact on more lying behavior, and Sarkozy-prime made such impact even stronger. Overall, the research findings suggest that lying can be triggered by external influencers such as leaders, presidents and politicians in the organizations. Our findings have provided valuable insights to organizational leaders and managers in their personnel management practice, especially in the intervention of lying behavior. Our findings also have offered new insights to explain non-conscious lying behavior

Overcoming the barriers of teaching physical examination at the bedside: More than just curriculum design

Background: Physicians in training must achieve a high degree of proficiency in performing physical examinations and must strive to become experts in the field. Concerns are emerging about physicians' abilities to perform these basic skills, essential for clinical decision making. Learning at the bedside has the potential to support skill acquisition through deliberate practice. Previous skills improvement programs, targeted at teaching physical examinations, have been successful at increasing the frequency of performing and teaching physical examinations. It remains unclear what barriers might persist after such program implementation. This study explores residents' and physicians' perceptions of physical examinations teaching at the bedside following the implementation of a new structured bedside curriculum: What are the potentially persisting barriers and proposed solutions for improvement? Methods: The study used a constructivist approach using a qualitative inductive thematic analysis that was oriented to construct an understanding of the barriers and facilitators of physical examination teaching in the context of a new bedside curriculum. Participants took part in individual interviews and subsequently focus groups. Transcripts were coded and themes were identified. Results: Data analyses yielded three main themes: (1) the culture of teaching physical examination at the bedside is shaped and threatened by the lack of hospital support, physicians' motivation and expertise, residents' attitudes and dependence on technology, (2) the hospital environment makes bedside teaching difficult because of its chaotic nature, time constraints and conflicting responsibilities, and finally (3) structured physical examination curricula create missed opportunities in being restrictive and pose difficulties in identifying patients with findings. Conclusions: Despite the implementation of a structured bedside curriculum for physical examination teaching, our study suggests that cultural, environmental and curriculum-related barriers remain important issues to be addressed. Institutions wishing to develop and implement similar bedside curricula should prioritize recruitment of expert clinical teachers, recognizing their time and efforts. Teaching should be delivered in a protected environment, away from clinical duties, and with patients with real findings. Physicians must value teaching and learning of physical examination skills, with multiple hands-on opportunities for direct role modeling, coaching, observation and deliberate practice. Ideally, clinical teachers should master the art of combining both patient care and educational activities

Rewriting a Deep Generative Model

A deep generative model such as a GAN learns to model a rich set of semantic and physical rules about the target distribution, but up to now, it has been obscure how such rules are encoded in the network, or how a rule could be changed. In this paper, we introduce a new problem setting: manipulation of specific rules encoded by a deep generative model. To address the problem, we propose a formulation in which the desired rule is changed by manipulating a layer of a deep network as a linear associative memory. We derive an algorithm for modifying one entry of the associative memory, and we demonstrate that several interesting structural rules can be located and modified within the layers of state-of-the-art generative models. We present a user interface to enable users to interactively change the rules of a generative model to achieve desired effects, and we show several proof-of-concept applications. Finally, results on multiple datasets demonstrate the advantage of our method against standard fine-tuning methods and edit transfer algorithms.Comment: ECCV 2020 (oral). Code at https://github.com/davidbau/rewriting. For videos and demos see https://rewriting.csail.mit.edu

Chronic Losartan Administration Reduces Mortality and Preserves Cardiac but Not Skeletal Muscle Function in Dystrophic Mice

Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6–9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the study endpoint, 88% of treated mice were alive compared to only 44% of untreated (p = 0.05). No difference in skeletal muscle morphology, function, or fibrosis was noted in losartan-treated animals. Cardiac function was significantly preserved with losartan treatment, with a trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal muscle disease progression, suggesting that other pathways that trigger fibrosis dominate over angiotensin II in skeletal muscle long term, unlike the situation in the heart. Our study suggests that ARB may be an important prophylactic treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle disease

Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey

BACKGROUND: Persistence is a key factor for long-term blood pressure control, which is of high prognostic importance for patients at increased cardiovascular risk. Here we present the results of a post-marketing survey including 4769 hypertensive patients treated with irbesartan in 886 general practices in Switzerland. The goal of this survey was to evaluate the tolerance and the blood pressure lowering effect of irbesartan as well as the factors affecting persistence in a large unselected population. METHODS: Prospective observational survey conducted in general practices in all regions of Switzerland. Previously untreated and uncontrolled pre-treated patients were started with a daily dose of 150 mg irbesartan and followed up to 6 months. RESULTS: After an observation time slightly exceeding 4 months, the average reduction in systolic and diastolic blood pressure was 20 (95% confidence interval (CI) -19.6 to -20.7 mmHg) and 12 mmHg (95% CI -11.4 to -12.1 mmHg), respectively. At this time, 26% of patients had a blood pressure < 140/90 mmHg and 60% had a diastolic blood pressure < 90 mmHg. The drug was well tolerated with an incidence of adverse events (dizziness, headaches,...) of 8.0%. In this survey more than 80% of patients were still on irbesartan at 4 month. The most important factors predictive of persistence were the tolerability profile and the ability to achieve a blood pressure target ≤ 140/90 mmHg before visit 2. Patients who switched from a fixed combination treatment tended to discontinue irbesartan more often whereas those who abandoned the previous treatment because of cough (a class side effect of ACE-Inhibitors) were more persistent with irbesartan. CONCLUSION: The results of this survey confirm that irbesartan is effective, well tolerated and well accepted by patients, as indicated by the good persistence. This post-marketing survey also emphasizes the importance of the tolerability profile and of achieving an early control of blood pressure as positive predictors of persistence

Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design

Background Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss. This has been supported by the recently published EMPA-REG trial which showed a striking 38 and 35 % reduction in cardiovascular death and HF hospitalisation respectively. Methods The REFORM trial is a novel, phase IV randomised, double blind, placebo controlled clinical trial that has been ongoing since March 2015. It is designed specifically to test the safety and efficacy of the SLGT2 inhibitor, dapagliflozin, on diabetic patients with known HF. We utilise cardiac-MRI, cardio-pulmonary exercise testing, body composition analysis and other tests to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard of care over a 1 year observation period. The primary outcome is to detect the change in left ventricular (LV) end systolic and LV end diastolic volumes. The secondary outcome measures include LV ejection fraction, LV mass index, exercise tolerance, fluid status, quality of life measures and others. Conclusions This trial will be able to determine if SGLT2 inhibitor therapy produces potentially beneficial effects in patients with DM and HF, thereby replacing current medications as the drug of choice when treating patients with both DM and HF

Cardiovascular and renal outcomes of renin-angiotensin system blockade in adult patients with diabetes mellitus: a systematic review with network meta-analyses

Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes