The End of Single-Molecule Envy

Molecular interactions can be detected using single engineered ion channels as stochastic sensors. This approach is used to examine events between a kinase and an inhibitor peptide tethered to an engineered channel [1] showing agreement with macroscopic biochemical data, as well as a tantalizing surprise

Recommendations to support deprescribing medications late in life

It is widely acknowledged that patients—particularly those late in life—are frequently exposed to the harms of medication. To minimize these harms, several frameworks have been developed by which prescribing can be optimized. In the context of diminishing life expectancy, these frameworks can be used to reduce medications that are no longer necessary, but appear to fall short of actual guidelines that incorporate a consideration of stopping medications. In this commentary, we present recommendations that could be incorporated into prescribing processes for all healthcare professionals and, ultimately, used to support the rationalization or deprescribing of medication in diminished life expectancy. We frame these recommendations in the same context as guidance for the initiation and discontinuation of implantable cardiac devices and argue that the two processes—with regards to decision-making—should be the same. We present our recommendations with preventive medication use in mind, and use statin therapy as an illustrative example

Repaying the Education Debt Through Professional Development: An Equity Audit

Dr. Ladson-Billings has reframed the commonly understood achievement gap as an education debt that is owed to all students, especially Black and Brown students. Research suggests the difference in achievement as measured by assessment, attendance, and graduation is marked by racial lines. One-way school districts have tried to address race-based injustices is by providing equity-focused professional development (PD) for district employees. This is a qualitative critical case study focused on understanding how a school district located in Western, Washington is working toward creating a more equitable education for all students. The research team used components of an equity audit to analyze the alignment of the current recommendations outlined in three of the District’s public documents to Courageous Conversations About Race—a source of equity PD the District is currently implementing. The research team collected and analyzed data from public documents using a combination of document analysis methods. The research team triangulated the findings to identify recommendations for the District in implementing PD that will help it to meet its goal in providing equitable education for all students, especially those who are currently furthest from educational justice

Distinct mechanisms of Drosophila CRYPTOCHROME-mediated light-evoked membrane depolarization and in vivo clock resetting.

Drosophila CRYPTOCHROME (dCRY) mediates electrophysiological depolarization and circadian clock resetting in response to blue or ultraviolet (UV) light. These light-evoked biological responses operate at different timescales and possibly through different mechanisms. Whether electron transfer down a conserved chain of tryptophan residues underlies biological responses following dCRY light activation has been controversial. To examine these issues in in vivo and in ex vivo whole-brain preparations, we generated transgenic flies expressing tryptophan mutant dCRYs in the conserved electron transfer chain and then measured neuronal electrophysiological phototransduction and behavioral responses to light. Electrophysiological-evoked potential analysis shows that dCRY mediates UV and blue-light-evoked depolarizations that are long lasting, persisting for nearly a minute. Surprisingly, dCRY appears to mediate red-light-evoked depolarization in wild-type flies, absent in both cry-null flies, and following acute treatment with the flavin-specific inhibitor diphenyleneiodonium in wild-type flies. This suggests a previously unsuspected functional signaling role for a neutral semiquinone flavin state (FADH•) for dCRY. The W420 tryptophan residue located closest to the FAD-dCRY interaction site is critical for blue- and UV-light-evoked electrophysiological responses, while other tryptophan residues within electron transfer distance to W420 do not appear to be required for light-evoked electrophysiological responses. Mutation of the dCRY tryptophan residue W342, more distant from the FAD interaction site, mimics the cry-null behavioral light response to constant light exposure. These data indicate that light-evoked dCRY electrical depolarization and clock resetting are mediated by distinct mechanisms

Missed opportunities: unnecessary medicine use in patients with lung cancer at the end of life: an international cohort study

Aims The aims of the current study were: (i) to examine the prescribing of preventative medication in a cohort of people with advanced lung cancer on hospital admission and discharge across different healthcare systems; and (ii) to explore the factors that influence preventative medication prescribing at hospital discharge. Methods A retrospective cohort study was conducted across two centres in the UK and the US. The prescribing of preventative medication was examined at hospital admission and discharge for patients who died of lung cancer. A zero‐inflated negative binomial regression model was used to examine the association between preventative medications at discharge and patient‐ and hospital‐based factors. The classes of preventative medication prescribed included were: vitamins and minerals, and antidiabetic, antihypertensive, antihyperlipidaemic and antiplatelet medications. Results In the UK site (n = 125), the mean number of preventative medications prescribed was 1.9 [standard deviation (SD) 1.7) on admission, and 1.7 (SD 1.7) on discharge, and in the US site (n = 191) the mean was 2.6 (SD 2.2) on admission and 1.9 (SD 2.2) on discharge. The model found a significant association between the number of preventative drugs prescribed on admission and the number on discharge; it also found a significant association between the total number of drugs prescribed on discharge and the number of preventative medications on discharge. Other indicators related to patient and hospital factors were not significantly associated with the number of preventative medications supplied on discharge. Conclusions The use of preventative medication was common in lung cancer patients, despite undergoing discharge. Patient‐ and hospital‐based factors did not influence the prescribing of preventative medication

Inappropriate prescribing of preventative medication in patients with life-limiting illness: a systematic review

Objectives To systematically review the literature to examine the methods used to identify inappropriate prescribing of preventative medication in patients with life-limiting illness and to detail the nature of medications prescribed. Methods A systematic literature search of 4 databases was undertaken (MEDLINE, EMBASE, CINAHL, PsycINFO) from inception to April 2015 to identify peer-reviewed, observational studies assessing inappropriate prescribing of preventative medication in patients with life-limiting illness. Inclusion criteria were: participants had a life-limiting illness; prescribed/dispensed/using preventative medication; medication appropriateness assessed as a specific study aim or outcome. Results We found 19 studies meeting our eligibility criteria. The methods used to assess medication appropriateness included criteria developed for the elderly such as the Beers Criteria, and Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, Delphi consensus and expert clinical opinion. Lipid-regulating drugs (12 studies), antihypertensive (11 studies) and antidiabetic medications (9 studies) were the most common classes of inappropriate medication identified. Conclusions Patients with life-limiting illnesses are prescribed preventative medications considered inappropriate in the context of diminished life expectancy. The way in which preventative medication appropriateness is assessed in patients with life-limiting illness varies considerably—with some methodologies utilising criteria previously developed for elderly populations. Given this lack of standardisation, improving the prescribing in this context requires an approach that is specifically designed and validated for populations with life-limiting illness

CA1-projecting subiculum neurons facilitate object-place learning.

Recent anatomical evidence suggests a functionally significant back-projection pathway from the subiculum to the CA1. Here we show that the afferent circuitry of CA1-projecting subicular neurons is biased by inputs from CA1 inhibitory neurons and the visual cortex, but lacks input from the entorhinal cortex. Efferents of the CA1-projecting subiculum neurons also target the perirhinal cortex, an area strongly implicated in object-place learning. We identify a critical role for CA1-projecting subicular neurons in object-location learning and memory, and show that this projection modulates place-specific activity of CA1 neurons and their responses to displaced objects. Together, these experiments reveal a novel pathway by which cortical inputs, particularly those from the visual cortex, reach the hippocampal output region CA1. Our findings also implicate this circuitry in the formation of complex spatial representations and learning of object-place associations

Atopic dermatitis and autoimmunity: the occurrence of autoantibodies and their association with disease severity

Atopic dermatitis (AD) is a widespread condition that appears to be increasing in prevalence and severity worldwide, yet the underlying mechanisms are not well understood. Recent research has identified various similarities between AD and autoimmune conditions, as well as indicating that there may be an association between AD and autoimmunity. This systematic review evaluates the association between AD and autoimmunity, as well as between severity of disease in AD and autoimmunity, with an emphasis on the associations with autoantibodies. MEDLINE (1946 to December 2017) and Embase (1974 to December 2017) databases were searched. Further relevant articles were retrieved from reference lists. Only studies measuring direct indicators of autoimmunity, in humans, were included. Qualitative analysis was carried out for allstudies. In addition, quantitative analysis was used to evaluate prevalence of IgE autoantibodies and antinuclear antibodies (ANAs) in AD patients and control subjects. The Mantel-Haenszel method was used with a random-effects model. Twenty-eight studies assessed the occurrence of autoantibodies in AD patients and 16 studies were used to evaluate association between disease severity and autoantibodies. Pooled analysis from 14 studies, involving 986 AD patients and 441 control subjects, showed that IgE autoantibodies were significantly more prevalent in patients with AD (P less than 00001) than control subjects. Similar analysis was carried out for ANAs, with eight studies that involved 1045 AD patients and 1273 control subjects. ANAs were significantly more prevalent in patients with AD (P = 0.003). This quantitative analysis supported an association between AD and IgE autoantibodies, as well as between AD and ANAs. There was insufficient data to make similar conclusions for other indicators of autoimmunity. The weight of evidence also suggests an association between IgE autoantibodies and disease severity. There was insufficient evidence to make this link for other indicators of autoimmunity