Reduced atrial contribution to left ventricular filling in patients with severe tricuspid regurgitation after tricuspid valvulectomy: A Doppler echocardiographic study

AbstractPatients undergoing valvulectomy for isolated tricuspid valve endocarditis offer the unique opportunity to study the effects of acquired right ventricular volume overload on left ventricular filling in persons free of pulmonary hypertension and preexisting left heart disease. Eleven patients who had undergone total or partial removal of the tricuspid valve were compared with 11 age-matched control subjects; Doppler echocardiographic techniques were used to quantify changes in left ventricular filling and to relate them to changes in left ventricular and left atrial geometry caused by right ventricular and right atrial distension.The late diastolic fractional transmitral flow velocity integral, a measure of the left atrial contribution to left ventricular filling, was significantly decreased in patients undergoing tricuspid valvulectomy compared with control subjects (0.22 ± 0.11 versus 0.32 ± 0.09; p < 0.04). Severe tricuspid regurgitation in these patients resulted in marked right atrial distension, reversal of the normal interatrial septal curvature and compression of the left atrium such that left atrial area was significantly smaller than in control subjects (5.9 ± 2.2 versus 8.6 ± 1.2 cm2/m2; p < 0.005).Acting as a receiving chamber, the left ventricle was maximally compressed by the volume-overloaded right ventricle in late diastole coincident with the timing of atrial systole, resulting in a significant increase in the left ventricular eccentricity index compared with that in control subjects (1.35 ± 0.14 versus 1.03 ± 0.1; p < 0.001). Thus, right ventricular volume overload due to severe tricuspid regurgitation results in left heart geometric alterations that decrease left atrial preload, impair left ventricular receiving chamber characteristics and reduce the atrial contribution to total left ventricular filling

Emerging Areas of Science: Recommendations for Nursing Science Education from the Council for the Advancement of Nursing Science Idea Festival

The Council for the Advancement of Nursing Science aims to “facilitate and recognize life-long nursing science career development” as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee (IFAC) to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2005 National Research Council report Advancing The Nation\u27s Health Needs and the 2010 American Association of Colleges of Nursing Position Statement on the Research-Focused Doctorate Pathways to Excellence, the IFAC specifically addressed the capacity of PhD programs to prepare nursing scientists to conduct cutting-edge research in the following key emerging and priority areas of health sciences research: omics and the microbiome; health behavior, behavior change, and biobehavioral science; patient-reported outcomes; big data, e-science, and informatics; quantitative sciences; translation science; and health economics. The purpose of this article is to (a) describe IFAC activities, (b) summarize 2014 discussions hosted as part of the Idea Festival, and (c) present IFAC recommendations for incorporating these emerging areas of science and technology into research-focused doctoral programs committed to preparing graduates for lifelong, competitive careers in nursing science. The recommendations address clearer articulation of program focus areas; inclusion of foundational knowledge in emerging areas of science in core courses on nursing science and research methods; faculty composition; prerequisite student knowledge and skills; and in-depth, interdisciplinary training in supporting area of science content and methods

Emerging Areas of Nursing Science and PhD Education for The 21\u3csup\u3est\u3c/sup\u3e Century: Response to Commentaries

We respond to commentaries from the American Academy of Nursing, the American Association of Colleges of Nursing, and the National Institute of Nursing Research on our thoughts about integrating emerging areas of science into nursing PhD programs. We identify areas of agreement and focus our response on cross-cutting issues arising from cautions about the unique focus of nursing science and how best to proceed with incorporation of emerging areas of science into nursing PhD programs

Characterisation of two snake toxin-targeting human monoclonal immunoglobulin G antibodies expressed in tobacco plants

Current snakebite antivenoms are based on polyclonal animal-derived antibodies, which can neutralize snake venom toxins in envenomed victims, but which are also associated with adverse reactions. Therefore, several efforts within antivenom research aim to explore the utility of recombinant monoclonal antibodies, such as human immunoglobulin G (IgG) antibodies, which are routinely used in the clinic for other indications. In this study, the feasibility of using tobacco plants as bioreactors for expressing full-length human monoclonal IgG antibodies against snake toxins was investigated. We show that the plant-produced antibodies perform similarly to their mammalian cell-expressed equivalents in terms of in vitro binding. Complete neutralization was achieved by both the plant and mammalian cell-produced anti-α-cobratoxin antibody. The feasibility of using plant-based expression systems may potentially make it easier for laboratories in resource-poor settings to work with human monoclonal IgG antibodies

Using the Social Skills Improvement System (SSiS) Rating Scales to assess social skills in youth with Down syndrome

Introduction and MethodsThis study provides preliminary data on the Social Skills Improvement System (SSiS) Rating Scales Parent Form to measure social skills in a sample of 124 children and adolescents with Down syndrome (DS) ages 6–17 years.ResultsOverall, participants demonstrated relatively mild symptoms, with the sample’s average standard score falling within 1 standard deviation from the mean of the normative sample for the social skills (M = 92, SD = 15) and problem behaviors (M = 104, SD = 12) domains (normative sample M = 100, SD = 15 for both domains). However, a wide range of scores was observed across the sample for the composite and subscale scores. Differential patterns were also observed by subscale. For some subscales (i.e., Cooperation, Assertion, Responsibility, Engagement, Externalizing, Hyperactivity/Inattention, and Autism Spectrum), a disproportionate number of participants scored in the below average (i.e., lower levels of social skills) or above average (i.e., more symptomatic in problem behaviors or autism spectrum) range relative to the normative sample; for other subscales (i.e., Communication, Empathy, Self-Control, Bullying, and Internalizing), participants’ score distribution aligned more closely to that of the normative sample. SSiS composite scores correlated in the expected directions with standardized measures of autism characteristics, executive function, and expressive language.DiscussionThis study provides some of the first evidence validating the use of the SSiS in youth with DS, filling a gap in standardized measures of social functioning in this population

Young people’s use of e-cigarettes in Wales, England and Scotland before and after introduction of EU Tobacco Products Directive regulations: a mixed-method natural experimental evaluation

Background: Young people's experimentation with e-cigarettes has increased in recent years, although regular use remains limited. EU Tobacco Products Directive (TPD) regulations introduced packet warnings, advertising restrictions, and regulated nicotine strength from 2016, in part due to concerns regarding use by young people. This paper examines e-cigarette use trajectories before and after TPD. Methods: E-cigarette use data were obtained from School Health Research Network/Health Behaviour in School-aged Children surveys in Wales and Smoking Drinking and Drug Use surveys in England. Data from Wales were analysed using segmented logistic regression, with before and after regression analyses of English data. Semi-structured group interviews included young people aged 14-16 years in Wales, England and Scotland in 2017 and 2018. Results: In Wales, ever use of e-cigarettes increased over time, but under a range of assumptions, growth did not appear to continue post-TPD. A small and non-significant change in trend was observed post-implementation (OR=0.96; 95%CI=0.91 to 1.01), which increased in size and significance after adjusting for ever smoking (OR=0.93; 95%CI=0.88 to 0.98). There was little increase in regular e-cigarette use from 2015 to 2017 in Wales. However, ever and regular use increased from 2014 to 2016 in England. Young people in all nations described limited interactions with components of TPD, while describing e-cigarette use as a ‘fad’, which had begun to run its course. Conclusions: This study provides preliminary evidence that young people's e-cigarette experimentation may be plateauing in UK nations. The extent to which this arises from regulatory changes, or due to a fad having begun to lose its appeal among young people in the UK countries, remains unclear. These trends contrast to those observed in North America, where newer products whose EU market entry and marketing have been impacted by TPD, have gained traction among young people. Long-term monitoring of e-cigarette use trends and perceptions among young people remain vital

Potent Nonnucleoside Reverse Transcriptase Inhibitors Target HIV-1 Gag-Pol

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) target HIV-1 reverse transcriptase (RT) by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation

Challenges in managing urinary tract infection and the potential of a point-of-care test guided care in primary care: an international qualitative study

Background Little is known about clinicians’ experiences of using a point-of-care test (POCT) to inform management of urinary tract infection (UTI) in general practice. Aim To explore experiences of using the Flexicult test to inform management of UTI and views on requirements for an optimal POCT to inform successful implementation. Design & setting Telephone interviews with 35 primary care clinicians and healthcare professionals in Wales, England, Spain, and the Netherlands, who had participated in a trial of the Flexicult POCT for UTI based on urine culture. Method Thematic analysis of semi-structured interviews. Results Most primary care clinicians interviewed agreed on the need for a POCT in UTI management, and that the Flexicult POCT delivered quicker results than laboratory results used in usual care, reassured patients, boosted their confidence in decision-making, and reminded them about antibiotic stewardship. However, clinicians also reported difficulties in interpreting results, limitations on when the Flexicult could be used, and concerns that testing all patients would strain care delivery and prolong patient discomfort when delaying decisions until a non-rapid POCT result was available. An optimal POCT would produce more rapid results, and be reliable and easy to use. Uptake into routine care would be enhanced by: clear guidance on which patients should be tested; training for interpreting ‘grey area’ results; reiterating that even ‘straightforward’ cases might be better managed with a test; clear messages about stopping unnecessary antibiotics versus completing a course; and better self-management strategies to accompany implementation of delayed, or non-prescription of, antibiotics. Conclusion Primary care clinicians believe that POCT tests could play a useful role in the management of UTI and gave clear recommendations for successful implementation