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Abstract Background The ability to manipulate, edit and process DNA and protein sequences has rapidly become a necessary skill for practicing biologists across a wide swath of disciplines. In spite of this, most everyday sequence manipulation tools are distributed across several programs and web servers, sometimes requiring installation and typically involving frequent switching between applications. To address this problem, here we have developed BioWord, a macro-enabled self-installing template for Microsoft Word documents that integrates an extensive suite of DNA and protein sequence manipulation tools. Results BioWord is distributed as a single macro-enabled template that self-installs with a single click. After installation, BioWord will open as a tab in the Office ribbon. Biologists can then easily manipulate DNA and protein sequences using a familiar interface and minimize the need to switch between applications. Beyond simple sequence manipulation, BioWord integrates functionality ranging from dyad search and consensus logos to motif discovery and pair-wise alignment. Written in Visual Basic for Applications (VBA) as an open source, object-oriented project, BioWord allows users with varying programming experience to expand and customize the program to better meet their own needs. Conclusions BioWord integrates a powerful set of tools for biological sequence manipulation within a handy, user-friendly tab in a widely used word processing software package. The use of a simple scripting language and an object-oriented scheme facilitates customization by users and provides a very accessible educational platform for introducing students to basic bioinformatics algorithms.

Background: Using electronic health records (EHRs), in addition to claims, to systematically identify patients with factors associated with adverse outcomes (geriatric risk) among older adults can prove beneficial for population health management and clinical service delivery., Objective: To define and compare geriatric risk factors derivable from claims, structured EHRs, and unstructured EHRs, and estimate the relationship between geriatric risk factors and health care utilization., Research Design: We performed a retrospective cohort study of patients enrolled in a Medicare Advantage plan from 2011 to 2013 using both administrative claims and EHRs. We defined 10 individual geriatric risk factors and a summary geriatric risk index based on diagnosed conditions and pattern matching techniques applied to EHR free text. The prevalence of geriatric risk factors was estimated using claims, structured EHRs, and structured and unstructured EHRs combined. The association of geriatric risk index with any occurrence of hospitalizations, emergency department visits, and nursing home visits were estimated using logistic regression adjusted for demographic and comorbidity covariates., Results: The prevalence of geriatric risk factors increased after adding unstructured EHR data to structured EHRs, compared with those derived from structured EHRs alone and claims alone. On the basis of claims, structured EHRs, and structured and unstructured EHRs combined, 12.9%, 15.0%, and 24.6% of the patients had 1 geriatric risk factor, respectively; 3.9%, 4.2%, and 15.8% had ≥2 geriatric risk factors, respectively. Statistically significant association between geriatric risk index and health care utilization was found independent of demographic and comorbidity covariates. For example, based on claims, estimated odds ratios for having 1 and ≥2 geriatric risk factors in year 1 were 1.49 (P<0.001) and 2.62 (P<0.001) in predicting any occurrence of hospitalizations in year 1, and 1.32 (P<0.001) and 1.34 (P=0.003) in predicting any occurrence of hospitalizations in year 2., Conclusions: The results demonstrate the feasibility and potential of using EHRs and claims for collecting new types of geriatric risk information that could augment the more commonly collected disease information to identify and move upstream the management of high-risk cases among older patients.

Background: Type 2 diabetes mellitus is characterized by relative insulin deficiency and insulin resistance. Features suggesting severe insulin resistance include acanthosis nigricans, hyperandrogenism, weight loss, and recurrent hospital admissions for diabetic ketoacidosis. In rare circumstances, hyperglycemia persists despite administration of massive doses of insulin. In these cases, it is important to consider autoimmune etiologies for insulin resistance, such as type B insulin resistance and insulin antibody-mediated extreme insulin resistance, which carry high morbidity and mortality if untreated. Encouragingly, immunomodulatory regimens have recently been published that induce remission at high rates., Methods/results: We describe 3 cases of extreme insulin resistance mediated by anti-insulin receptor autoantibodies or insulin autoantibodies. All cases were effectively treated with an immunomodulatory regimen., Conclusion: Although cases of extreme insulin resistance are rare, it is important to be aware of autoimmune causes, recognize suggestive signs and symptoms, and pursue appropriate diagnostic evaluation. Prompt treatment with immunomodulators is key to restoring euglycemia in patients with autoimmune etiologies of insulin resistance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neuropsychological assessment is known to be influenced by expectancy effects, which can either enhance (placebo) or diminish (nocebo) cognitive performance. Research suggests that the response expectancy effect is influenced by various individual and situational factors and that the placebo effect results in an increase in monitoring processes as measured indirectly. However, the impact on monitoring processes has not yet been studied by direct measures such as Judgement Of Learning (JOL). This study aimed to investigate the response expectancy effect on various neuropsychological tasks, including a task that directly assesses monitoring capacities (JOL). In addition to determining which cognitive functions are influenced by the expectancy effect, this study examined the moderating role of the self-transcendence dimension of personality. Eighty healthy subjects were exposed to three bogus conditions presented as allegedly having a positive, negative, or no impact on cognitive capacities. Then they completed, in random order, three blocks of tasks (executive, attentional, and memory), one in each condition. Results showed an effect of negative instructions on flexibility (poorer performance) and memory (better performance) scores. Furthermore, positive instructions led to better explicit monitoring capacities (JOL) than the neutral condition. These effects were moderated by self-transcendence, as only participants with moderate or high self-transcendence exhibited these effects. Overall, our results showed that the response expectancy effect emerges from a combination of individual and cognitive factors.

This study investigates the fluorescence quenching of a poly(p-phenyleneethynylene) (1) based polyelectrolyte by positively charged and neutral macromolecules. This work shows that the change in the fluorescence yield of 1 depends on a number of factors, including electrostatic, hydrophobic, and energy transfer interactions with the quencher and also changes in the solution conditions such as concentration and ionic strength. The fluorescence quenching is attributed to the formation of aggregates that form upon addition of different quenchers to a solution of 1 and/or the solution conditions. The extent of 1's aggregation is shown to depend on the type of interaction between the polymer and the quencher, the concentration of the polymer, and the ionic strength of the solution.

Melanosomes and lipofuscin were isolated from 14-, 59-, and 76-year-old, human retinal pigment epithelium specimens and examined. The morphological features of these samples were studied by scanning electron microscopy and atomic force microscopy, and the photoionization properties were examined by photoelectron emission microscopy. Ovoid- and rod-shaped melanosomes were observed. The size of the granules and the distribution between the two shapes show no significant age-dependent change. However, there is a higher occurrence of irregularly shaped aggregates of small round granules in older samples which suggests degradation or damage to melanosomes occurs with age. The melanosomes from the 14-year-old donor eye are well characterized by a single photoionization threshold, 4.1 eV, while the two older melanosomes exhibit two thresholds around 4.4 and 3.6 eV. Lipofuscin from both young and old cells show two thresholds, 4.4 and 3.4 eV. The similarity of the potentials observed for aged melanosomes and lipofuscin suggest that the lower threshold in the melanosome sample reflects lipofuscin deposited the surface of the melanosome. The amount, however, is not sufficient to alter the density of the melanosome, and therefore these granules do not separate in a sucrose gradient at densities characteristic of the typical melanolipofuscin granule. These data suggest that thin deposits of lipofuscin on the surface of retinal pigment epithelium melanosomes are common in the aged eye and that this renders the melanosomes more pro-oxidant.