Red foliage color reliably indicates low host quality and increased metabolic load for development of an herbivorous insect

Abstract Plant chemical defense and coevolved detoxification mechanisms in specialized herbivorous insects are fundamental in determining many insect-plant interactions. For example, Brassicale plants protect themselves from herbivory by producing glucosinolates, but these secondary metabolites are effectively detoxified by larvae of Pierid butterflies. Nevertheless, not all Brassicales are equally preferred by these specialist herbivores. Female Pieris butterflies avoid laying eggs on anthocyanin-rich red foliage, suggesting red color is a visual cue affecting oviposition behavior. In this study, we reared P. brassicae larvae on green and red cabbage leaves, to determine whether foliage color reliably indicates host plant quality. We did not find a difference in survival rates or maximal larval body mass in the two food treatments. However, larvae feeding on red cabbage leaves exhibited significantly lower growth rates and longer durations of larval development. Interestingly, this longer development was coupled with a higher consumption rate of dry food matter. The lower ratio of body mass gain to food consumption in larvae feeding on red cabbage leaves was coupled with significantly higher (ca. 10 %) larval metabolic rates. This suggests that development on red foliage may incur an increased metabolic load associated with detoxification of secondary plant metabolites. Energy and oxygen allocation to detoxification could come at the expense of growth and thus compromise larval fitness as a result of extended development. From an evolutionary perspective, red foliage color may serve as an honest defensive cue, as it reliably indicates the plant's low quality as a substrate for larval development

Activated Microglia in Cortical White Matter Across Cognitive Aging Trajectories

Activation of microglia, the primary mediators of inflammation in the brain, is a major component of gliosis and neuronal loss in a number of age-related neurodegenerative disorders, such as Alzheimer’s disease (AD). The role of activated microglia in white matter, and its relationship with cognitive decline during aging are unknown. The current study evaluated microglia densities in the white matter of postmortem specimens from cognitively normal young adults, cognitively normal older adults, and cognitive “SuperAgers,” a unique group of individuals over age 80 whose memory test scores are at a level equal to or better than scores of 50-to-65-year-olds. Whole hemisphere sections from cognitively normal old, young, and “SuperAgers” were used to quantify densities of human leukocyte antigen-D related (HLA-DR)-positive activated microglia underlying five cortical regions. Statistical findings showed a significant main effect of group on differences in microglia density where cognitively normal old showed highest densities. No difference between SuperAgers and young specimens were detected. In two autopsied SuperAgers with MRI FLAIR scans available, prominent hyperintensities in periventricular regions were observed, and interestingly, examination of corresponding postmortem sections showed only sparse microglia densities. In conclusion, activated microglia appear to respond to age-related pathologic changes in cortical white matter, and this phenomenon is largely spared in SuperAgers. Findings offer insights into the relationship between white matter neuroinflammatory changes and cognitive integrity during aging

Hybrid Tele-Health Approaches to Allied Health Services: A Scoping Review

Background and aim: During the past 2 years (during COVID-19), tele-health services by allied health professions (health professions other than doctors and nurses) have become widespread; uptake was almost immediate due to restrictions of social distancing and limitations on in-person services. In the aftermath of the pandemic, as limitations were receded, tele-health services substantially subsided, despite their many advantages. Hybrid tele-health is a service modality that combines in-person and remote services, thus reaping the demonstrated benefits of both. Still, research that defines the terminology of the service, existing models, outcomes, “best practices” and evaluation of service effectiveness is sparse. The aim of this review is to formulate a multidimensional, conceptual framework of hybrid tele-health services for adults and children requiring allied health interventions. The guiding research question is: What are the existing definitions, models, and outcome measures of hybrid allied health interventions for people across the lifespan? Methods: A scoping review will systematically map evidence and identify existing models for hybrid administration of allied health services. According to the framework of Arksey and O’Malley (2005), two independent researchers will systematically and iteratively search databases (PubMed, Cochrane Library, Embase, CINAHL, ERIC, Scopus, PsycInfo, Science Direct, Web of Science, Google Scholar) for peer-reviewed manuscripts and conference proceedings that examined or described hybrid interventions. Based on the results, we will develop a multidimensional conceptual framework of hybrid tele-health services for adults and children requiring allied health interventions Expected results: This scoping review will provide a comprehensive synthesis of existing models, uses, definitions, and outcomes for hybrid telehealth services. The resulting framework will recommend uniform terminology and assist in identifying gaps in the literature regarding potential uses of and need for research of hybrid models. Importance to Medicine: Understanding hybrid telehealth services is expected to guide the development of future services in Israel and beyond, capitalizing on knowledge established during COVID-19, and will inform ongoing research and policies, thus improving accessibility to professional allied health care

Clinical pharmacist led hospital-wide direct oral anticoagulant stewardship program

Abstract Introduction In the past decade, direct-acting oral anticoagulants (DOAC) have been introduced to medical practice for several indications, with a wide range of dosing regimens. As both over- and under-dosing might lead to life-threatening events, development of methods promoting safe and effective utilization of these agents is imperative. The Hadassah Clinical Pharmacy team initiated a hospital-wide program, for monitoring and promoting safe and effective prescription of DOAC during hospitalization. This study describes the types of drug related problems addressed and the program’s performance in terms of consultation rates and physician acceptance. Methods Electronic medical records throughout the hospital were screened for DOAC orders. All DOAC orders were assessed by a clinical pharmacist for potentially-inappropriate prescribing. When potentially-inappropriate prescribing or a drug-related problem was identified, the clinical pharmacist provided consultation on management options. In specific cases, additional guidance was provided by coagulation and pharmacology specialists. Data on patient characteristics, clinical pharmacist consultations, and physician response was retrospectively retrieved for the first six months of 2017. Characteristics of patients with and without consultations were compared, consultations were categorized by the recommended management of the drug related problem, and physician acceptance rates were evaluated by category. Results During the evaluated period, 585 patients with DOAC orders were identified. Patients were evenly distributed by gender, and age averaged 78 years. Most patients received apixaban (75%) followed by rivaroxaban (14%) and dabigatran (11%), and most (63%) received “reduced dose” regimens. Clinical pharmacists provided 258 consultations for 210 patients, regarding anticoagulation management, such that more than one in three patients on DOAC had potentially inappropriate prescribing or drug related problems. Consultations included alerts regarding potentially inappropriate DOAC doses and recommendations to increase (29%) or decrease (5%) the dose, potentially inappropriate concomitant antiplatelet agents (20%), need for DOAC level monitoring (23%), and alerts regarding other drug related problems (23%). More than 70% of recommendations were accepted by the attending physician. Conclusion Due to the complexity of DOAC management, potentially-inappropriate prescribing and drug related problems are common. Multidisciplinary collaborative projects including review and consultation by clinical pharmacists are an effective method of improving management of patients on DOAC. Trial registration Retrospectively registered at clinicaltrials.gov, NCT03527615

Phenotypically concordant distribution of pick bodies in aphasic versus behavioral dementias

Abstract Pick’s disease (PiD) is a subtype of the tauopathy form of frontotemporal lobar degeneration (FTLD-tau) characterized by intraneuronal 3R-tau inclusions. PiD can underly various dementia syndromes, including primary progressive aphasia (PPA), characterized by an isolated and progressive impairment of language and left-predominant atrophy, and behavioral variant frontotemporal dementia (bvFTD), characterized by progressive dysfunction in personality and bilateral frontotemporal atrophy. In this study, we investigated the neocortical and hippocampal distributions of Pick bodies in bvFTD and PPA to establish clinicopathologic concordance between PiD and the salience of the aphasic versus behavioral phenotype. Eighteen right-handed cases with PiD as the primary pathologic diagnosis were identified from the Northwestern University Alzheimer’s Disease Research Center brain bank (bvFTD, N = 9; PPA, N = 9). Paraffin-embedded sections were stained immunohistochemically with AT8 to visualize Pick bodies, and unbiased stereological analysis was performed in up to six regions bilaterally [middle frontal gyrus (MFG), superior temporal gyrus (STG), inferior parietal lobule (IPL), anterior temporal lobe (ATL), dentate gyrus (DG) and CA1 of the hippocampus], and unilateral occipital cortex (OCC). In bvFTD, peak neocortical densities of Pick bodies were in the MFG, while the ATL was the most affected in PPA. Both the IPL and STG had greater leftward pathology in PPA, with the latter reaching significance (p < 0.01). In bvFTD, Pick body densities were significantly right-asymmetric in the STG (p < 0.05). Hippocampal burden was not clinicopathologically concordant, as both bvFTD and PPA cases demonstrated significant hippocampal pathology compared to neocortical densities (p < 0.0001). Inclusion-to-neuron analyses in a subset of PPA cases confirmed that neurons in the DG are disproportionately burdened with inclusions compared to neocortical areas. Overall, stereological quantitation suggests that the distribution of neocortical Pick body pathology is concordant with salient clinical features unique to PPA vs. bvFTD while raising intriguing questions about the selective vulnerability of the hippocampus to 3R-tauopathies

Cardiologic Manifestations in Omicron‐Type Versus Wild‐Type COVID‐19: A Systematic Echocardiographic Study

Background Information about the cardiac manifestations of the Omicron variant of COVID‐19 is limited. We performed a systematic prospective echocardiographic evaluation of consecutive patients hospitalized with the Omicron variant of COVID‐19 infection and compared them with similarly recruited patients were propensity matched with the wild‐type variant. Methods and Results A total of 162 consecutive patients hospitalized with Omicron COVID‐19 underwent complete echocardiographic evaluation within 24 hours of admission and were compared with propensity‐matched patients with the wild‐type variant (148 pairs). Echocardiography included left ventricular (LV) systolic and diastolic, right ventricular (RV), strain, and hemodynamic assessment. Echocardiographic parameters during acute infection were compared with historic exams in 62 patients with the Omicron variant and 19 patients with the wild‐type variant who had a previous exam within 1 year. Of the patients, 85 (53%) had a normal echocardiogram. The most common cardiac pathology was RV dilatation and dysfunction (33%), followed by elevated LV filling pressure (E/e′ ≥14, 29%) and LV systolic dysfunction (ejection fraction <50%, 10%). Compared with the matched wild‐type cohort, patients with Omicron had smaller RV end‐systolic areas (9.3±4 versus 12.3±4 cm2; P=0.0003), improved RV function (RV fractional‐area change, 53.2%±10% versus 39.7%±13% [P<0.0001]; RV S′, 12.0±3 versus 10.7±3 cm/s [P=0.001]), and higher stroke volume index (35.6 versus 32.5 mL/m2; P=0.004), all possibly related to lower mean pulmonary pressure (34.6±12 versus 41.1±14 mm Hg; P=0.0001) and the pulmonary vascular resistance index (P=0.0003). LV systolic or diastolic parameters were mostly similar to the wild‐type variant‐matched cohort apart from larger LV size. However, in patients who had a previous echocardiographic exam, these LV abnormalities were recorded before acute Omicron infection, but not in the wild‐type cohort. Numerous echocardiographic parameters were associated with higher in‐hospital mortality (LV ejection fraction, stroke volume index, E/e′, RV S′). Conclusions In patients with Omicron, RV function is impaired to a lower extent compared with the wild‐type variant, possibly related to the attenuated pulmonary parenchymal and/or vascular disease. LV systolic and diastolic abnormalities are as common as in the wild‐type variant but were usually recorded before acute infection and probably reflect background cardiac morbidity. Numerous LV and RV abnormalities are associated with adverse outcome in patients with Omicron

Differentiating among stages of cognitive impairment: Comparisons of versions two and three of the National Alzheimer- s Coordinating Center (NACC) Uniform Data Set (UDS) neuropsychological test battery

BackgroundNational Institute on Aging (NIA)- funded Alzheimer- s Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer- s Coordinating Center (NACC) Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS was implemented in 2015 and included several changes to its neuropsychological battery, replacing the previous version [Version 2 (V2)]. The current study compares the V3 and V2 neuropsychological batteries with respect to their ability to distinguish among categories of cognitive impairment captured by the Clinical Dementia Rating (CDR) global scores representing either no cognitive impairment (CDR=0), questionable or mild cognitive impairment (CDR=0.5) or mild stage of dementia (CDR=1.0).MethodData from the NACC UDS V2 and V3 neuropsychological batteries were examined. There were 16,935 unique subjects from V2 and 5022 unique subjects from V3 aged 60 years and older with CDR global score - ¤ 1. To reduce the influence of practice effects, only data from their first assessment was used. To control for inequalities in sample sizes between V2 and V3, we identified an approximately equal number of subjects from V2 within each CDR group. Receiver Operating Characteristics Area under Curve (ROC- AUC) in differentiating stages of cognitive impairment were compared and optimal cut- points based on Youden- s J scores were calculated.ResultROC- AUCs from all of the V3 neuropsychological tests were comparable in their ability to differentiate CDR global scores with the corresponding tests in V2, despite the fact that V3 participants included more subjects at earlier stage of CDR 0.5. UDS V3 composite scores yielded similar ROC- AUCs to the best performing individual test within each domain, while the Montreal Cognitive Assessment (MoCA) total score yielded higher ROC- AUCs than any individual MoCA index scores. Racial differences in differentiating between CDR=0 and CDR=0.5 were also found.ConclusionA nonproprietary suite of neuropsychological tests in UDS V3 provided similar discriminative ability to tests in UDS V2 to distinguish categories of cognitive impairment. Optimal cut- points calculated in this study will be useful for clinical diagnosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163944/1/alz040648.pd

Differentiating among stages of cognitive impairment in aging: Version 3 of the Uniform Data Set (UDS) neuropsychological test battery and MoCA index scores

IntroductionFederally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.5, and 1.MethodsFirst, we matched participants receiving V2 tests (V2 cohort) and V3 tests (V3 cohort) in their cognitive functions using tests common to both versions. Then, we compared receiver-operating characteristic (ROC) area under the curve in differentiating CDRs for the remaining tests.ResultsSome V3 tests performed better than V2 tests in differentiating between CDR 0.5&nbsp;and 0, but the improvement was limited to Caucasian participants.DiscussionFurther efforts to improve the ability for early identification of cognitive decline among diverse racial groups are required

Differentiating among stages of cognitive impairment in aging: Version 3 of the Uniform Data Set (UDS) neuropsychological test battery and MoCA index scores

Federally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.5, and 1. First, we matched participants receiving V2 tests (V2 cohort) and V3 tests (V3 cohort) in their cognitive functions using tests common to both versions. Then, we compared receiver-operating characteristic (ROC) area under the curve in differentiating CDRs for the remaining tests. Some V3 tests performed better than V2 tests in differentiating between CDR 0.5 and 0, but the improvement was limited to Caucasian participants. Further efforts to improve the ability for early identification of cognitive decline among diverse racial groups are required