Effects of Healthy and Neuropathological Aging on Autobiographical Memory: A Meta-Analysis of Studies Using the Autobiographical Interview.

OBJECTIVES: A meta-analytic review was conducted to assess the effects of healthy aging, amnestic mild cognitive impairment (MCI), and Alzheimer's disease (AD) on naturalistic autobiographical memory using the Autobiographical Interview, a widely used, standardized assessment that derives measures of internal (episodic) and external (nonepisodic) details from freely recalled autobiographical narratives. METHODS: A comprehensive literature search identified 21 aging, 6 MCI, and 7 AD studies (total N = 1,556 participants). Summary statistics for internal and external details for each comparison (younger vs older or MCI/AD vs age-matched comparison groups) and effect size statistics were extracted and summarized using Hedges' g (random effects model) and adjusted for the presence of publication bias. RESULTS: The pattern of reduced internal and elevated external details in aging was robust and consistent across nearly all 21 studies. MCI and-to a greater extent-AD were associated with reduced internal details, whereas the external detail elevation faded with MCI and AD. Although there was evidence of publication bias on reporting of internal detail effects, these effects remained robust after correction. DISCUSSION: The canonical changes to episodic memory observed in aging and neurodegenerative disease are mirrored in the free recall of real-life events. Our findings indicate that the onset of neuropathology overwhelms the capacity of older adults to draw upon distributed neural systems to elaborate on past experiences, including both episodic details specific to identified events and nonepisodic content characteristic of healthy older adults' autobiographical narratives.

Procedures to Evaluate Inflammatory and Pathological Changes During Allergic Airway Inflammation.

Cellular inflammation, with elevated levels of Th1/Th2 cytokines, airway mucus hypersecretion, and thickening of the airway smooth muscle, are characteristic features of the allergic lung. Assessment of pathophysiological changes in allergic lungs serves as an important tool to determine disease progression and understand the underlying mechanisms of pathogenesis. This can be achieved by evaluating the lung tissue for inflammation and airway structural changes along with the measurement of important pro-inflammatory mediators such as Th1/Th2 cytokines and eotaxins. This chapter describes procedures to histologically evaluate inflammatory and pathological changes observed during allergic airway inflammation using lung tissue from mice.

Pulmonary delivery of ORMDL3 short hairpin RNA - a potential tool to regulate allergen-induced airway inflammation.

Aim/Purpose: Exposure to various allergens has been shown to increase expression of ORMDL3 in the lung in models of allergic asthma. Studies using genetically modified (transgenic or knock out) mice have revealed some of the functions of ORMDL3 in asthma pathogenesis, although amid debate. The goal of this study was to use targeted post-transcriptional downregulation of ORMDL3 in allergen-challenged wild-type (WT) mice by RNA interference to further elucidate the functional role of ORMDL3 in asthma pathogenesis and evaluate a potential therapeutic option.Methods: Allergen (ovalbumin [OVA])-challenged WT mice were administered intranasally (i.n) with a single dose of five short hairpin RNA (shRNA) constructs with different target sequence for murine ORMDL3 cloned in a lentiviral vector or with the empty vector (control). Mice were evaluated for allergen-induced airway hyperresponsiveness (AHR) and various features of airway inflammation after 72 hours.Results: I.n administration of a single dose of ORMDL3 shRNAs to OVA-challenged mice resulted in reduction of ORMDL3 gene expression in the lungs associated with a significant reduction in AHR to inhaled methacholine and in the number of inflammatory cells recruited in the airways, specifically eosinophils, as well as in airway mucus secretion compared to OVA-challenged mice that received the empty vector. Administration of ORMDL3 shRNAs also significantly inhibited levels of IL-13, eotaxin-2 and sphingosine in the lungs. Additionally, ORMDL3 shRNAs significantly inhibited the allergen-mediated increase in monohexyl ceramides C22:0 and C24:0.Conclusions: Post-transcriptional down regulation of ORMDL3 in allergic lungs using i.n-delivered ORMDL3 shRNA (akin to inhaled therapy) attenuates development of key features of airway allergic disease, confirming the involvement of ORMDL3 in allergic asthma pathogenesis and serving as a model for a potential therapeutic strategy.

Testing the impact of emotional mood and cue characteristics on detailed autobiographical memory retrieval.

Autobiographical memory retrieval is impacted by emotion, whether from an individual's mood state or a retrieval cue. Here, we addressed two questions concerning how emotion from these two sources affects the remembering of autobiographical experiences. The first question concerns whether emotional mood and retrieval cues both reliably impact the details and content of a recalled autobiographical memory. The second question concerns to what extent distinct emotional dimensions of retrieval cues-valence and arousal-individually impact the way these memories are recalled. Across three experiments, young adult participants described the details of autobiographical experiences in response to cue words that varied in emotional valence (Experiment 1) or both emotional valence and arousal (Experiments 2 and 3) under two mood states (happy or sad). Memory descriptions were scored for the number of specific episodic (internal) and nonepisodic (external) details as well as for overall emotional tone. Experiment 1 demonstrated that cue valence more reliably predicted the number of episodic details and tone of the memories than mood. Experiment 2 and 3 further explored this reported cue effect by comparing memory recollection to cues that systematically varied in both valence and arousal. Generally, we found that highly arousing cues led to memories described with more episodic details while cue valence predicted the emotional tone of the memory. We discuss how these dimensions of emotionality (i.e., valence and arousal) bias cued autobiographical memory recall and the implications these results have on models of memory. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Effect Of Dual sEH/COX-2 Inhibition on Allergen-Induced Airway Inflammation.

Arachidonic acid metabolites resulting from the cyclooxygenase (COX), lipoxygenase, and cytochrome P450 oxidase enzymatic pathways play pro- and anti-inflammatory roles in allergic airway inflammation (AAI) and asthma. Expression of COX-2 and soluble epoxide hydrolase (sEH) are elevated in allergic airways and their enzymatic products (e.g., prostaglandins and diols of epoxyeicosatrienoic acids, respectively) have been shown to participate in the pathogenesis of AAI. Here, we evaluated the outcome of inhibiting the COX-2 and sEH enzymatic pathways with a novel dual inhibitor, PTUPB, in A. alternata-induced AAI. Allergen-challenged mice were administered with 10 or 30 mg/kg of PTUPB, celecoxib (selective COX-2 inhibitor), t-TUCB (selective sEH inhibitor) or vehicle daily by gavage and evaluated for various features of AAI. PTUPB and t-TUCB at 30 mg/kg, but not celecoxib, inhibited eosinophilic infiltration and significantly increased levels of anti-inflammatory EETs in the lung tissue of allergen-challenged mice. t-TUCB significantly inhibited allergen-induced IL-4 and IL-13, while a less pronounced reduction was noted with PTUPB and celecoxib. Additionally, t-TUCB markedly inhibited eotaxin-2, an eosinophil-specific chemokine, which was only marginally reduced by PTUPB and remained elevated in celecoxib-treated mice. PTUPB or t-TUCB administration reversed allergen-induced reduction in levels of various lipid mediators in the lungs, with only a minimal effect noted with celecoxib. Despite the anti-inflammatory effects, PTUPB or t-TUCB did not reduce allergen-induced airway hyperresponsiveness (AHR). However, development of structural changes in the allergic airways, such as mucus hypersecretion and smooth muscle hypertrophy, was significantly inhibited by both inhibitors. Celecoxib, on the other hand, inhibited only airway smooth muscle hypertrophy, but not mucus hypersecretion. In conclusion, dual inhibition of COX-2 and sEH offers no additional advantage relative to sEH inhibition alone in attenuating various features associated with A. alternata-induced AAI, while COX-2 inhibition exerts only moderate or no effect on several of these features. Dual sEH/COX-2 inhibition may be useful in treating conditions where eosinophilic inflammation co-exists with pain-associated inflammation.

Hydrological and biogeochemical controls governing the speciation and accumulation of selenium in a wetland influenced by mine drainage.

Controls governing the speciation and accumulation of Se in a 3.7-ha marsh influenced by mine drainage were assessed through examination of water balance, water quality, sediment, and plant tissue components. Over the 8-mo study period (April through November, 2009), mean monthly flows ranged from 1600 to 2300 m3 d-1 (hydraulic retention time of 1-3 d). Total Se concentrations in the marsh outflow were lower than the inflow by 0.4 to 6.2 µg L-1 (mean difference = 3.3 µg L-1 ), illustrating Se removal. The Se accumulation pathways are illustrated by elevated concentrations of Se in sediments (3-35 mg kg-1 dry wt) as well as in below-ground (2-41 mg kg-1 dry wt; mean = 10 mg kg-1 dry wt) and above-ground (0.8-6.3 mg kg-1 dry wt; mean = 2 mg kg-1 dry wt) emergent plant tissues. Redox stratification in the shallow water column had a marked effect on Se speciation and behavior, illustrating bottom water removal of dissolved selenate in suboxic horizons and increased mobility of dissolved organo-Se. Mass balance data yielded inflow and outflow loading rates for Se of 27 and 23 g d-1 , respectively (net accumulation rate of 4 g d-1 or 0.11 mg m2 d-1 ). The rate of accumulation as calculated from the mass balance agrees with independently measured rates of Se accumulation in sediments for the site (3.6-8.1 g d-1 or 0.10-0.22 mg m-2 d-1 ). Environ Toxicol Chem 2018;37:1824-1838. © 2018 SETAC.

Hypoglycemia and severe lactic acidosis in a dog following metformin exposure.

Hypoglycemia and lactic acidosis are rare complications with metformin use in humans. As metformin is not commonly used in veterinary medicine, severe adverse effects secondary to exposure are not known. Awareness of potentially life-threatening complications with metformin exposure is an important addition to the veterinary literature.

Biogeochemical mechanisms of selenium exchange between water and sediments in two contrasting lentic environments.

The biogeochemical mechanisms of Se exchange between water and sediments in two contrasting lentic environments were assessed through examination of Se speciation in the water column, porewater, and sediment. High-resolution (7 mm) vertical profiles of <0.45 µm Se species across the sediment-water interface demonstrate that the behavior of dissolved Se(VI), Se(IV), and organo-Se are closely linked to redox conditions as revealed by porewater profiles of redox-sensitive species (dissolved O2, NO3-, Fe, Mn, SO4(2-), and ΣH2S). At both sites Se(VI) is removed from solution in suboxic near-surface porewaters demonstrating that the sediments are serving as diffusive sinks for Se. X-ray absorption near edge spectroscopy (XANES) of sediments suggests that elemental Se and organo-Se represent the dominant sedimentary sinks for dissolved Se. Dissolved Se(IV) and organo-Se are released to porewaters in the near-surface sediments resulting in the diffusive transport of these species into the water column, where between-site differences in the depths of release can be linked to differences in redox zonation. The presence or absence of emergent vegetation is proposed to present a dominant control on sedimentary redox conditions as well as on the recycling and persistence of reduced Se species in bottom waters.