Eye movements: viewing the window of opportunity

When searching with our eyes, parallel programming of successive eye movements ensures that visual information arriving too late to alter the direction of one eye movement can still influence the direction of the next. Paradoxically, we can use random noise to probe the time period over which visual information influences where next to direct our gaze.     

Fenestration: a window of opportunity for carnivorous plants

A long-standing but controversial hypothesis assumes that carnivorous plants employ aggressive mimicry to increase their prey capture success. A possible mechanism is that pitcher plants use aggressive mimicry to deceive prey about the location of the pitcher''s exit. Specifically, species from unrelated families sport fenestration, i.e. transparent windows on the upper surfaces of pitchers which might function to mimic the exit of the pitcher. This hypothesis has not been evaluated against alternative hypotheses predicting that fenestration functions to attract insects from afar. By manipulating fenestration, we show that it does not increase the number of Drosophila flies or of two ant species entering pitchers in Sarracenia minor nor their retention time or a pitcher''s capture success. However, fenestration increased the number of Drosophila flies alighting on the pitcher compared with pitchers of the same plant without fenestration. We thus suggest that fenestration in S. minor is not an example of aggressive mimicry but rather functions in long-range attraction of prey. We highlight the need to evaluate aggressive mimicry relative to alternative concepts of plant–animal communication.     

Cotranslational control of DNA transposition: a window of opportunity

Transposable elements are important in genome dynamics and evolution. Bacterial insertion sequences (IS) constitute a major group in number and impact. Understanding their role in shaping genomes requires knowledge of how their transposition activity is regulated and interfaced with the host cell. One IS regulatory phenomenon is a preference of their transposases (Tpases) for action on the element from which they are expressed (cis) rather than on other copies of the same element (trans). Using IS911, we show in vivo that activity in cis was ~200 fold higher than in trans. We also demonstrate that a translational frameshifting pause signal influences cis preference presumably by facilitating sequential folding and cotranslational binding of the Tpase. In vitro, IS911 Tpase bound IS ends during translation but not after complete translation. Cotranslational binding of nascent Tpase permits tight control of IS proliferation providing a mechanistic explanation for cis regulation of transposition involving an unexpected partner, the ribosome.     

A window of opportunity: timing protein degradation by trimming of sugars and ubiquitins

Of the many post-translational modifications of proteins, ubiquitination and N-glycosylation stand out because they are polymeric additions. In contrast to single-unit modifications, the fate of the modified protein is determined by the dynamic equilibrium of polymerization versus depolymerization, rather than by the initial addition itself. Notably, it is the trimming of sugar chains and elongation of polyubiquitin that target the protein to degradation. Recent research suggests that, for each process, special receptors recognize chains that reach an appropriate length and commit the conjugated substrate for proteasomal disposal. We propose that the 'magic numbers' are loss of at least three mannose residues from the initial chain, or extension to at least four ubiquitins. Although these processes are compartmentalized to either side of the endoplasmic reticulum (ER) membrane, some proteins are sequentially subjected to both because they transverse this membrane for ER-associated degradation.     

The window of opportunity: a relevant concept for axial spondyloarthritis

The window of opportunity is a concept critical to rheumatoid arthritis treatment. Early treatment changes the outcome of rheumatoid arthritis treatment, in that response rates are higher with earlier disease-modifying anti-rheumatic drug treatment and damage is substantially reduced. Axial spondyloarthritis is an inflammatory axial disease encompassing both nonradiographic axial spondyloarthritis and established ankylosing spondylitis. In axial spondyloarthritis, studies of magnetic resonance imaging as well as tumor necrosis factor inhibitor treatment and withdrawal studies all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This potential would suggest that the concept of a window of opportunity is relevant not only to rheumatoid arthritis but also to axial spondyloarthritis. The challenge now remains to identify high-risk patients early and to commence treatment without delay. Developments in risk stratification include new classification criteria, identification of clinical risk factors, biomarkers, genetic associations, potential antibody associations and an ankylosing spondylitis-specific microbiome signature. Further research needs to focus on the evidence for early intervention and the early identification of high-risk individuals.     

Arterial function in youth: window into cardiovascular risk.

Noninvasive measures of arterial function, such as intima-media thickness (IMT), endothelial function, and arterial stiffness are associated with and are prognostic of cardiovascular events in adults. Postmortem evidence, however, has established that the atherosclerotic process starts in childhood. Furthermore, cardiovascular morbidities in childhood disrupt arterial health and may lead to adverse outcomes in adulthood. Thus it is important to examine the developmental changes in IMT, endothelial function, and arterial stiffness in healthy youth in contrast to the arterial health profile of youth with cardiovascular morbidities and to examine the effect of lifestyle interventions. In healthy youth, IMT may increase slightly, arterial stiffness increases, but there is no change in endothelial function from 5 to 20 years of age. In youth with cardiovascular risk factors there are larger increases in IMT and arterial stiffness, and reductions in endothelial function compared with healthy youth. The reduced arterial function in youth with cardiovascular risk factors may be related to the atherosclerotic process. Exercise and physical activity appear to exert a protective effect on arterial function, and exercise training can improve arterial function in children with cardiovascular risk factors. Furthermore, although diet alone can improve arterial function in children, the combination of exercise and diet appears to be more effective than either intervention alone. Future studies need to focus on the mechanism by which exercise and diet improve arterial function, the most effective types of diet and exercise, and if intervening in childhood leads to favorable outcomes in adulthood.     

An extended window of opportunity for G-CSF treatment in cerebral ischemia

Background  

Granulocyte-colony stimulating factor (G-CSF) is known as a powerful regulator of white blood cell proliferation and differentiation in mammals. We, and others, have shown that G-CSF is effective in treating cerebral ischemia in rodents, both relating to infarct size as well as functional recovery. G-CSF and its receptor are expressed by neurons, and G-CSF regulates apoptosis and neurogenesis, providing a rational basis for its beneficial short- and long-term actions in ischemia. In addition, G-CSF may contribute to re-endothelialisation and arteriogenesis in the vasculature of the ischemic penumbra. In addition to these trophic effects, G-CSF is a potent neuroprotective factor reliably reducing infarct size in different stroke models.     

Comparative cardiovascular development: improving the conceptual framework

Immature vertebrates-either as an embryo in an egg, as free-living larva, or as an in utero fetus, are clearly not just small versions of adults. Their cardiovascular physiology (and doubtlessly other aspects of physiology) differs from that of adults both qualitatively and quantitatively. Yet, comparative cardiovascular physiologists have been relatively conservative in constructing a new (or at least modified) conceptual framework for the understanding of developmental cardiovascular physiology. We recommend that this framework rely less on the established cardiovascular truisms for adult cardiovascular physiology that are proving to be less useful and in instances even inaccurate for interpreting development of the heart and vasculature. We have suggested that three methodologies in particular be incorporated to a greater extent in studies of comparative cardiovascular development: (a) emphasis on multivariate approaches; (b) differentiation between absolute (extrinsic) and relative (intrinsic) time for development, and; (c) employment of time lines for both intra- and interspecific comparisons of the ontogeny of cardiovascular processes. While certainly none of these approaches are novel and others have previously dwelt at length on their importance in other contexts, we feel that the emerging framework for investigating cardiovascular physiological development would benefit from incorporating these and other approaches into experimental design as well as data analysis. Failing to do so results in a heavy dependence on analytical approaches typically used for adults, and thus under-appreciates the novelty and complexity of the developing vertebrate cardiovascular system.     

Neonate human remains: a window of opportunity to the molecular study of ancient syphilis

Ancient DNA (aDNA) analysis can be a useful tool in bacterial disease diagnosis in human remains. However, while the recovery of Mycobacterium spp. has been widely successful, several authors report unsuccessful results regarding ancient treponemal DNA, casting doubts on the usefulness of this technique for the diagnosis of ancient syphilis. Here, we present results from an analysis of four newborn specimens recovered from the crypt of "La Ermita de la Soledad" (XVI-XVII centuries), located in the province of Huelva in the southwest of Spain. We extracted and analyzed aDNA in three independent laboratories, following specific procedures generally practiced in the aDNA field, including cloning of the amplified DNA fragments and sequencing of several clones. This is the most ancient case, reported to date, from which detection of DNA from T. pallidum subspecies pallidum has been successful in more than one individual, and we put forward a hypothesis to explain this result, taking into account the course of the disease in neonate individuals.     

Evening chronotype is associated with poor cardiovascular health and adverse health behaviors in a diverse population of women

ABSTRACT

Chronotype reflects time of day preferences for performing daily activities. Previous research within Asian and European cohorts indicates evening chronotype is associated with elevated cardiometabolic risk. However, evidence is limited from population-based US cohorts, particularly among women in whom evening chronotype prevalence may become higher after middle-age, coinciding with life stages associated with higher cardiovascular disease (CVD) risk. This cross-sectional study evaluated associations of chronotype with overall cardiovascular health (CVH), health behaviors, and cardiometabolic risk factors among 506 women (mean age = 37 ± 16y, 62% racial/ethnic minority) in the American Heart Association (AHA)’s Go Red for Women Strategically-Focused Research Network cohort at Columbia University (New York City, NY, USA). Chronotype was assessed using the validated Morningness-Eveningness Questionnaire (MEQ) and categorized as “evening”, “intermediate”, and “morning” chronotypes. Health behaviors (diet, physical activity, and sleep) were assessed using validated questionnaires. Anthropometrics, clinical blood pressure, and blood biomarkers were assessed at the clinic visit. CVH was evaluated using the AHA Life’s Simple 7 (LS7) metrics; LS7 scores of 0–8 and 9–14 were considered indicative of poor and moderate-to-high CVH, respectively. Linear and logistic regression models adjusted for age, race/ethnicity, education, health insurance, and menopausal status were used to examine associations of MEQ scores and chronotype categories with overall CVH, clinical cardiometabolic risk factors, and health behaviors. Overall, 13% of women identified as evening chronotypes, while 55% and 32% reported being intermediate and morning types. In linear models, higher MEQ scores were associated with higher AHA LS7 scores (β(SE) = 0.02(0.01); p = .014), indicative of more favorable CVH, and with health behaviors not included in the LS7. Higher MEQ scores were also associated with lower Pittsburgh Sleep Quality Index, i.e. better sleep quality, (β(SE) = ?0.07(0.02), p < .0001), lower insomnia severity (β(SE) = ?0.14(0.01), p < .0001), shorter time to fall asleep (β(SE) = ?0.28(0.14), p = .044), and less sedentary time (β(SE) = ?0.11(0.03), p = .001). In logistic regression models, evening chronotype, compared to intermediate/morning type, was associated with higher odds of having poor CVH (OR(95%CI):2.41(1.20–4.85)), not meeting AHA diet (OR(95%CI):2.89(1.59–5.23)) and physical activity guidelines (OR(95%CI):1.78(1.03–3.07)), and having short sleep (OR(95%CI):2.15(1.24–3.73)) or insomnia (OR(95%CI):2.69(1.53–4.75)). The evening type compared to morning type was also associated with being a current smoker (OR(95%CI):2.14(1.02–4.52)) and having poor sleep quality (OR(95%CI:2.35(1.27–4.37)) and long sleep onset latency (OR(95%CI:1.89(1.00–3.56)). In our cohort of women, evening chronotype was related to poor CVH, likely driven by its influence on health behaviors. These findings, although warranting confirmation prospectively in other populations, suggest chronotype is an important factor to consider and possibly target when designing lifestyle interventions for CVD prevention.     

Role of prophylactic coronary revascularisation in improving cardiovascular outcomes during non-cardiac surgery: A narrative review

Coronary revascularisation has been a topic of debate for over three decades in patients undergoing high-risk non-cardiac surgery. The paradigm shifted from routine coronary angiography toward stress test guided decision-making based on larger randomised trials. However, this paradigm is challenged by relatively newer data where routine coronary angiography and revascularisation is shown to improve perioperative cardiovascular outcomes. We review major studies performed over a long period including more contemporary data with regard to the 2014 American College of Cardiology/American Heart Association as well as 2014 European Society of Cardiology guideline on perioperative cardiovascular evaluation of patients undergoing non-cardiac surgery.     

Lymphatic Filariasis (Elephantiasis) Elimination: A public health success and development opportunity

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis, launched following World Health Assembly Resolution 50.29 (WHA 50.29), has been facilitated in its progress by new research findings, drug donations, the availability of diagnostic tools, disability management strategies to help those already suffering and the development of partnerships. The strategy recommended by the World Health Organization of annual treatment with a two-drug combination has proved safe. DISCUSSION: Using different approaches in several countries the elimination of lymphatic filariasis (LF) has been demonstrated to be feasible during earlier decades. These successes have been largely overlooked. However, the programme progress since 2000 has been remarkable - upscaling rapidly from 2 million treatments in 2000 to approximately 60 million in 2002. Around 34 countries had active programmes at the end of 2002. It is anticipated that there will be further expansion - but this will be dependent on additional resources becoming available. The programme also provides significant opportunities for other disease control programmes to deliver public health benefits on a large scale. Few public health programmes have upscaled so rapidly and so cost-effectively (<$0.03/treatment in some Asian settings) - one country treating 9-10 million people in a day (Sri Lanka). The LF programme is arguably the most effective pro-poor public health programme currently operating which is based on country commitment and partnerships supported by a global programme and alliance. Tables are provided to summarize programme characteristics, the benefits of LF elimination, opportunities for integration with other programmes and relevance to the Millennium Development Goals. SUMMARY: Lymphatic filariasis elimination is an "easy-to-do" inexpensive health intervention that provides considerable "beyond filariasis" benefits, exemplifies partnership and is easily evaluated. The success in global health action documented in this paper requires and deserves further support to bring to fruition elimination of lymphatic filariasis as a public health problem and health benefits to poor people. A future free of lymphatic filariasis will reduce poverty and bring better health to poor people, prevent disability, strengthen health systems and build partnerships.     

Review of cardiovascular risk factors in women

Background: Although cardiovascular disease (CVD) is the leading cause of death in women in the United States, a knowledge gap persists regarding the mechanisms and management of CVD in women. Before treatment can be optimized, the role of cardiovascular risk factors must be elucidated.Objective: This review provides an updated assessment of cardiovascular risk factors in women, with a focus on cardiometabolic risk.Methods: MEDLINE and Cochrane Library databases, and statistics from the National Health and Nutrition Examination Survey and the American Heart Association, were searched from 1990 to September 2008 using the following terms: cardiovascular risk factors, women, gender, cardiometabolic risk, abdominal obesity, and metabolic syndrome. Publications were classified as English-only original data, reviews, and clinical guidelines. Nonpublished data were excluded. Data were extracted by 2 reviewers independently.Results: Investigators performing multivariable predictive models have estimated that traditional risk factors account for ~70% of the variance in estimating cardiovascular events. However, substantial sex differences exist in the prevalence of traditional risk factors as well as in cardiovascular outcomes. Hypertension is more prevalent in men until the age of 59 years, but then contributes to greater morbidity in older women. Low levels of high-density lipoprotein and elevated triglyceride levels pose more of a threat to women, yet high levels of low-density lipoprotein pose equal risk for women and men. The CVD mortality rate is -3 times greater in people with diabetes than in those without diabetes. Among diabetic individuals, CVD mortality is slightly higher in women compared with men.Conclusions: Increased knowledge of gender-specific risks for CVD has led to national campaigns to educate women. In addition to traditional risk factors, cardiometabolic risk is an important consideration in women. Controversy exists regarding the exact definitions and usefulness of the term metabolic syndrome, but it is clear that the presence of certain factors contributes to increased morbidity and mortality in affected individuals. Abdominal obesity links insulin resistance, dyslipidemia, and hypertension through complex endocrine pathways. Current research is identifying gene × gender interactions, and continued research is necessary to explore the relationship of sex steroids and cardiovascular risk in both men and women.