LRP1 Functions as an Atheroprotective Integrator of TGFβ and PDGF Signals in the Vascular Wall: Implications for Marfan Syndrome

BACKGROUND: The multifunctional receptor LRP1 controls expression, activity and trafficking of the PDGF receptor-β in vascular smooth muscle cells (VSMC). LRP1 is also a receptor for TGFβ1 and is required for TGFβ mediated inhibition of cell proliferation. METHODS AND PRINCIPAL FINDINGS: We show that loss of LRP1 in VSMC (smLRP(−)) in vivo results in a Marfan-like syndrome with nuclear accumulation of phosphorylated Smad2/3, disruption of elastic layers, tortuous aorta, and increased expression of the TGFβ target genes thrombospondin-1 (TSP1) and PDGFRβ in the vascular wall. Treatment of smLRP1(−) animals with the PPARγ agonist rosiglitazone abolished nuclear pSmad accumulation, reversed the Marfan-like phenotype, and markedly reduced smooth muscle proliferation, fibrosis and atherosclerosis independent of plasma cholesterol levels. CONCLUSIONS AND SIGNIFICANCE: Our findings are consistent with an activation of TGFβ signals in the LRP1-deficient vascular wall. LRP1 may function as an integrator of proliferative and anti-proliferative signals that control physiological mechanisms common to the pathogenesis of Marfan syndrome and atherosclerosis, and this is essential for maintaining vascular wall integrity

Researching COVID to Enhance Recovery (RECOVER) Pregnancy Study: Rationale, Objectives and Design

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011

Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection

Introduction Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. Methods and findings We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV- 2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). Conclusions In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms

Your Money or Your Sense of Smell? A Comparative Analysis of the Sensory and Psychological Value of Olfaction

In public discourse, the sense of smell is typically characterized as the least important of the five senses. However, there are very little empirical data on this topic. Recently, much more attention has been brought to the sense of smell since olfactory dysfunction is a primary and often long-term symptom of COVID-19 infection. It was therefore of interest to expand research on the perceived value of olfaction in the current cultural condition. We developed a survey that directly compared the value of the senses of smell, hearing, and vision with each other and in relation to nine common items representing digital, material, personal, and physical commodities of varying social and emotional meaningfulness (phone, $10,000, favorite social media, online shopping, favorite streaming service, dream vacation, pet, hair, little left toe). In total, four hundred and seven female and male respondents comprising two life-stage groups (college students, general public adults) participated in our online survey study during winter&ndash;spring of 2021. The results reveal that the sense of smell was perceived as vastly less important than vision and hearing and much less valuable than various common commodities. We also found that life-stage and gender mediated our findings. For example, one-quarter of the college student respondents would give up their sense of smell in order to keep their phone and nearly half of all women would give up their sense of smell to keep their hair. Our data further illustrate that the senses of vision and hearing are valued relatively similarly. A number of questions arise from the present data and suggestions for ways in which our survey can be expanded and altered to address further research are discussed

The Role of Odor-Evoked Memory in Psychological and Physiological Health

This article discusses the special features of odor-evoked memory and the current state-of-the-art in odor-evoked memory research to show how these unique experiences may be able to influence and benefit psychological and physiological health. A review of the literature leads to the conclusion that odors that evoke positive autobiographical memories have the potential to increase positive emotions, decrease negative mood states, disrupt cravings, and reduce physiological indices of stress, including systemic markers of inflammation. Olfactory perception factors and individual difference characteristics that would need to be considered in therapeutic applications of odor-evoked-memory are also discussed. This article illustrates how through the experimentally validated mechanisms of odor-associative learning and the privileged neuroanatomical relationship that exists between olfaction and the neural substrates of emotion, odors can be harnessed to induce emotional and physiological responses that can improve human health and wellbeing

Odor-associative learning and emotion: effects on perception and behavior

Introduction Associative learning, the process by which one event or item comes to be linked to another through experience, is critically involved in human cognition and behavior. It has been proposed that associative learning principles can explain human perceptual and cognitivebehavioral responses to odors A number of studies have shown that hedonic responses to odors are learned through specific experiences. Mennella and colleagues These examples illustrate that olfactory hedonics are learned on the basis of experience. A comparison of two studies shows how emotion is critically involved in this process. In the mid-1960s, in Britain, Moncrieff (1966) asked adult respondents to provide hedonic ratings to a battery of common odors. A similar study was conducted in the United States in the late 1970s (Cain and Johnson, 1978). Included in both studies was the odorant methyl salicylate (wintergreen). In the British study, wintergreen was given one of the lowest pleasantness ratings, whereas, in the US study it was given the highest. The reason for this difference is explained as follows. In Britain, the smell of wintergreen is associated with medicine and particularly for the participants in the 1966 study with analgesics that were popular during World War II, a time that these individuals would not remember fondly. Conversely, in the US, the smell of wintergreen is exclusively a candy mint smell and one that only has positive connotations. Neuroanatomy further supports the proposition that our olfactory system is especially prepared to learn the significance of odors. The orbitofrontal cortex, in addition to processing olfaction, is the area of the brain critical for assigning affective value to stimuli; in other words, assigning hedonic meaning. Furthermore, the amygdala which synapses directly with the olfactory nerve is critical for emotional associative learning Current experimental evidence To test the hypothesis that olfactory hedonic responses are acquired through associative learning with emotion, we conducted two experiments that varied with regard to whether a novel (&apos;target&apos;) odor was pre-experimentally pleasant or unpleasant and the emotional association that was linked to it was positive or negative In each experiment, participants were randomly assigned to an experimental group (odor + emotional association) and various control groups. Evaluations of the target odor and several &apos;anchor odors&apos; (familiar odors that were not explicitly part of the association procedures) were made several times throughout the study: (i) prior to the manipulation; (ii) post-manipulation; (iii) 24 h after the manipulation; and (iv) 1 week from the start date. The results from both experiments showed that evaluation of the target odor by all participants was comparable prior to the manipulations and responses to the anchor odors were unaffected by time or experimental condition. However, in each experiment, post-emotional manipulation ratings to the target odor were significantly altered in the experimental group and showed that odor perception had changed in accord with the emotional valence of the associated experience. When an &apos;unpleasant&apos; target odor was paired with a positive emotional experience, subsequent evaluations of that odor were more favorable and when a &apos;pleasant&apos; target odor was paired with a negative emotional experience, subsequent evaluations of that odor were more unpleasant. No such effects were seen in the control groups. These findings show that when a novel odor is paired with an emotional event, hedonic perception of that odor is altered in accord with the associated emotion. Although our study can not rule out the possibility of innate responding to odors, together with past empirical work and developmental and cross-cultural data it appears that emotion in conjunction with odor exposure is a powerful manipulator of subsequent odor preference. In order to investigate how emotional associative learning to odors can induce mood consistent changes in behavior we first examined children Odor-associative Learning and Emotion: Effects on Perception and Behavior Rachel S. Herz Department of Psychology, Brown University, Providence, RI 02912, USA Odor-associative Learning and Emotion i251 many puppies missing their tails as they could by the time a voice counted to 10 (90 s). Performance was assessed by the number of puppies correctly circled as a function of ambient odor condition (same, different, or no-odor). Results revealed that performance of participants in the different-odor and no-odor groups was the same. However, children who performed the task in the presence of the same odor circled significantly fewer puppies (had lower performance scores) than participants in any other group. This decrement in test scores was presumed to be due to decreased motivation elicited by the odor-mood connection among children in the same-odor group and not a decrement in ability, as the children were randomly allocated to group and were of comparable intellectual ability. This study provided support for the hypothesis that emotional experiences can become associated to odors and when re-presented influence behavior in a mood consistent manner. However, several questions concerning the relationship between olfaction, emotional associative learning and behavior remained. To validate the findings of In sum, past studies and current empirical work provide strong experimental evidence to support the hypothesis that odor hedonic perception and odor-related behavior result from a learned association between an odor and the emotional context in which the odor was first encountered. Further research exploring the full range of emotional associations, the situations in which they can be expressed and a detailed analysis of the classical conditioning mechanisms involved in odor-associative learning are now needed

Your Money or Your Sense of Smell? A Comparative Analysis of the Sensory and Psychological Value of Olfaction

In public discourse, the sense of smell is typically characterized as the least important of the five senses. However, there are very little empirical data on this topic. Recently, much more attention has been brought to the sense of smell since olfactory dysfunction is a primary and often long-term symptom of COVID-19 infection. It was therefore of interest to expand research on the perceived value of olfaction in the current cultural condition. We developed a survey that directly compared the value of the senses of smell, hearing, and vision with each other and in relation to nine common items representing digital, material, personal, and physical commodities of varying social and emotional meaningfulness (phone, $10,000, favorite social media, online shopping, favorite streaming service, dream vacation, pet, hair, little left toe). In total, four hundred and seven female and male respondents comprising two life-stage groups (college students, general public adults) participated in our online survey study during winter–spring of 2021. The results reveal that the sense of smell was perceived as vastly less important than vision and hearing and much less valuable than various common commodities. We also found that life-stage and gender mediated our findings. For example, one-quarter of the college student respondents would give up their sense of smell in order to keep their phone and nearly half of all women would give up their sense of smell to keep their hair. Our data further illustrate that the senses of vision and hearing are valued relatively similarly. A number of questions arise from the present data and suggestions for ways in which our survey can be expanded and altered to address further research are discussed

Changing Odor Hedonic Perception Through Emotional Associations in Humans

A long-standing debate in olfactory perception is whether hedonic responses to odors are learned or innate. To test the hypothesis that olfactory hedonic responses are acquired through associative learning with emotion, two experiments were conducted that varied with regard to whether a novel (“target” odor) was pre-experimentally pleasant or unpleasant and the emotional association was positive or negative. Participants were randomly assigned to an Experimental Group (odor + emotional association) and various Control Groups. Evaluations of the target odor and several common odors that were not explicitly part of the association procedures (anchor odors) were made: prior to the manipulations, postmanipulation, 24 h after the manipulation, and 1 week from the start date. In both experiments, evaluation of the target odor by all participants was comparable at premanipulation and responses to the anchor odors were unaffected by time or experimental condition. However in each experiment, post-emotional manipulation ratings to the target odor were significantly altered in the Experimental Groups and showed that odor perception had changed in accord with the emotional valence of the associated experience. These findings support the hypothesis that olfactory hedonic responses are learned through emotional associations and raise new methodological and theoretical questions for future research

Sensation & perception

xii, 507 p. ; 28 cm