Can dogs serve as stress mediators to decrease salivary cortisol levels in a population of liberal arts college undergraduate students?

The steroid hormone cortisol can be used to measure physiological stress in humans. The hypothalamic-pituitary-adrenal (HPA) axis synthesizes cortisol, and a negative feedback cycle regulates cortisol depending on an individual's stress level and/or circadian rhythm. Chronic stress of college undergraduate students is associated with various adverse health effects, including anxiety and depression. Reports suggest that stress levels have risen dramatically in recent years, particularly among university students dealing with intense academic loads in addition to COVID-19 pandemic-related uncertainty. The increasing rate of mental illness on college campuses necessitates the study of mediators potentially capable of lowering stress, and thus cortisol levels. Research on mediation techniques and coping mechanisms have gained traction to address the concerning levels of stress, including the employment of human-animal interaction sessions on college campuses. In this study, human-canine interaction as a stress mediation strategy for undergraduate students was investigated. We measured salivary cortisol levels in 73 college undergraduate students during a 60-min interaction period with a dog to determine whether human-canine interactions are effective in lowering cortisol levels and potentially reducing chronic stress typical of undergraduate students. Our results indicate that a human-canine interaction for 60 min is an effective method for significantly reducing salivary cortisol and stress levels among undergraduate college students. These findings support the expansion of animal visitation programs on college campuses to help students manage stress.

A non-canonical Raf function is required for dorsal-ventral patterning during Drosophila embryogenesis.

Proper embryonic development requires directional axes to pattern cells into embryonic structures. In Drosophila, spatially discrete expression of transcription factors determines the anterior to posterior organization of the early embryo, while the Toll and TGFß signalling pathways determine the early dorsal to ventral pattern. Embryonic MAPK/ERK signaling contributes to both anterior to posterior patterning in the terminal regions and to dorsal to ventral patterning during oogenesis and embryonic stages. Here we describe a novel loss of function mutation in the Raf kinase gene, which leads to loss of ventral cell fates as seen through the loss of the ventral furrow, the absence of Dorsal/NFκB nuclear localization, the absence of mesoderm determinants Twist and Snail, and the expansion of TGFß. Gene expression analysis showed cells adopting ectodermal fates much like loss of Toll signaling. Our results combine novel mutants, live imaging, optogenetics and transcriptomics to establish a novel role for Raf, that appears to be independent of the MAPK cascade, in embryonic patterning.

Application of optogenetic Amyloid-ß distinguishes between metabolic and physical damages in neurodegeneration.

The brains of Alzheimer's disease patients show a decrease in brain mass and a preponderance of extracellular Amyloid-ß plaques. These plaques are formed by aggregation of polypeptides that are derived from the Amyloid Precursor Protein (APP). Amyloid-ß plaques are thought to play either a direct or an indirect role in disease progression, however the exact role of aggregation and plaque formation in the aetiology of Alzheimer's disease (AD) is subject to debate as the biological effects of soluble and aggregated Amyloid-ß peptides are difficult to separate in vivo. To investigate the consequences of formation of Amyloid-ß oligomers in living tissues, we developed a fluorescently tagged, optogenetic Amyloid-ß peptide that oligomerizes rapidly in the presence of blue light. We applied this system to the crucial question of how intracellular Amyloid-ß oligomers underlie the pathologies of A. We use Drosophila, C. elegans and D. rerio to show that, although both expression and induced oligomerization of Amyloid-ß were detrimental to lifespan and healthspan, we were able to separate the metabolic and physical damage caused by light-induced Amyloid-ß oligomerization from Amyloid-ß expression alone. The physical damage caused by Amyloid-ß oligomers also recapitulated the catastrophic tissue loss that is a hallmark of late AD. We show that the lifespan deficit induced by Amyloid-ß oligomers was reduced with Li+ treatment. Our results present the first model to separate different aspects of disease progression.

Alzheimer's disease is a progressive condition that damages the brain over time. The cause is not clear, but a toxic molecule called Amyloid-ß peptide seems to play a part. It builds up in the brains of people with Alzheimer's disease, forming hard clumps called plaques. Yet, though the plaques are a hallmark of the disease, experimental treatments designed to break them down do not seem to help. This raises the question ­ do Amyloid-ß plaques actually cause Alzheimer's disease? Answering this question is not easy. One way to study the effect of amyloid plaques is to inject clumps of Amyloid-ß peptides into model organisms. This triggers Alzheimer's-like brain damage, but it is not clear why. It remains difficult to tell the difference between the damage caused by the injected Amyloid-ß peptides and the damage caused by the solid plaques that they form. For this, researchers need a way to trigger plaque formation directly inside animal brains. This would make it possible to test the effects of plaque-targeting treatments, like the drug lithium. Optogenetics is a technique that uses light to control molecules in living animals. Hsien, Kaur et al. have now used this approach to trigger plaque formation by fusing light-sensitive proteins to Amyloid-ß peptides in worms, fruit flies and zebrafish. This meant that the peptides clumped together to form plaques whenever the animals were exposed to blue light. This revealed that, while both the Amyloid-ß peptides and the plaques caused damage, the plaques were much more toxic. They damaged cell metabolism and caused tissue loss that resembled late Alzheimer's disease in humans. To find out whether it was possible to test Alzheimer's treatments in these animals, Hsien, Kaur et al. treated them with the drug, lithium. This increased their lifespan, reversing some of the damage caused by the plaques. Alzheimer's disease affects more than 46.8 million people worldwide and is the sixth leading cause of death in the USA. But, despite over 50 years of research, there is no cure. This new plaque-formation technique allows researchers to study the effects of amyloid plaques in living animals, providing a new way to test Alzheimer's treatments. This could be of particular help in studies of experimental drugs that aim to reduce plaque formation.

Exploring the Relationship between School Gardens, Food Literacy and Mental Well-Being in Youths Using Photovoice.

The goal of the project was to gain an understanding of the relationships between secondary school youth experiences in school gardens and their mental well-being. Over the course of five months, sixteen youths participated in a photovoice research project in which they expressed their personal experiences about food and gardening through photography and writing. The aspects of secondary school youths' life experiences affected by exposure to school gardens and their impact upon their well-being were identified. The youth explicitly associated relaxation with the themes of love and connectedness, growing food, garden as a place, cooking, and food choices. They were able to demonstrate and develop food literacy competency because of their engagement with the gardening and cooking activities. Youth clubs or groups were identified as a key enabler for connection with other youth and adults. Youth shared their food literacy experiences, observing that their engagement improved some aspect of their mental well-being. Through the photovoice process, the youth identified how their involvement in green spaces enabled connections with others, and highlighted aspects of personal health and personal growth, all of which contribute to their mental well-being.

Inhibition of amyloid-induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model.

The abnormal accumulation of ß-amyloid peptide (Aß) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aß-mediated neurotoxicity remain elusive, Aß has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione-derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET's potential to counteract Aß-toxicity in transgenic Caenorhabditis elegans overexpressing a human Aß peptide. The accumulation of Aß in this model leads to paralysis and premature death. We show that ET dose-dependently reduces Aß-oligomerization and extends the lifespan and healthspan of the nematodes.

Green space and serious psychological distress among adults and teens: A population-based study in California.

There has been mounting evidence for the beneficial effect of green space on mental health among adults, but studies on the same topics are lacking for teens in the US. This study aimed to fill in this research gap by utilizing data from California Health Interview Survey (CHIS) 2011-2014. A total of 81,102 households (composed of 4538 teens and 81,102 adults) were retained for main analyses. Surrounding greenness was assessed by the Normalized Difference Vegetation Index (NDVI) within varying buffers of home residence. Survey logistic regressions accounted for sampling weights and design were conducted to examine the effects of greenness on serious psychological distress (SPD), adjusted for major socio-demographic factors, neighborhood socioeconomic status (SES) and co-respondent's psychological distress level within the same household. An inter-quartile increment of NDVI in 350 m buffer predicted decreased odds of SPDs by 36% in teens (OR = 0.64, 95% CI = [0.46, 0.91]). Mediation analyses revealed that this association remained almost unchanged even after adjusting for social cohesion. The NDVI-SPD association of adults was found to be significant only in the older group (OR = 0.81, 95% CI = [0.68, 0.95]). This study is one of the first population-based US studies extending the epidemiological evidence for benefits of green space on mental health from adults to teens.

Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling.

There is growing interest in pharmacological interventions directly targeting the aging process. Pharmacological interventions against aging should be efficacious when started in adults and, ideally, repurpose existing drugs. We show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved aging pathways and mechanisms using drug combinations. Using this approach in C. elegans, we were able to slow aging and significantly extend healthy lifespan. To identify the mechanism of these drug synergies, we applied transcriptomics and lipidomics analysis. We found that drug interactions involved the TGF-ß pathway and recruited genes related with IGF signaling. daf-2, daf-7, and sbp-1 interact upstream of changes in lipid metabolism, resulting in increased monounsaturated fatty acid content and this is required for healthy lifespan extension. These data suggest that combinations of drugs targeting distinct subsets of the aging gene regulatory network can be leveraged to cause synergistic lifespan benefits.

Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5.

The highly conserved Wnt signaling pathway regulates cell proliferation and differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during canonical and non-canonical Wnt signaling. The specific details of how this process occurs have proven difficult to study, especially as Dsh appears to function as a switch between different branches of Wnt signaling. Here we focus on the membrane-proximal events that occur once Dsh is recruited to the membrane. We show that membrane-tethering of the Dsh protein is sufficient to induce canonical Wnt signaling activation even in the absence of the Wnt co-receptor Arrow/LRP5/6. We map the protein domains required for pathway activation in membrane tethered constructs finding that both the DEP and PDZ domains are dispensable for canonical signaling only in membrane-tethered Dsh, but not in untethered/normal Dsh. These data lead to a signal activation model, where Arrow is required to localize Dsh to the membrane during canonical Wnt signaling placing Dsh downstream of Arrow.

Epidermal Growth Factor Pathway Signaling in Drosophila Embryogenesis: Tools for Understanding Cancer.

EGF signaling is a well-known oncogenic pathway in animals. It is also a key developmental pathway regulating terminal and dorsal-ventral patterning along with many other aspects of embryogenesis. In this review, we focus on the diverse roles for the EGF pathway in Drosophila embryogenesis. We review the existing body of evidence concerning EGF signaling in Drosophila embryogenesis focusing on current uncertainties in the field and areas for future study. This review provides a foundation for utilizing the Drosophila model system for research into EGF effects on cancer.

Unequal Protection: Secondhand Smoke Threatens Health of Tenants in Multi-Unit Housing in Los Angeles.

Secondhand smoke is dangerous to a person's health at any level of exposure. Yet policies that prevent smoking are not in place for a majority of market-rate multi-unit housing complexes, according to a new survey of nearly 1,000 apartment dwellers in the city of Los Angeles. Approximately 37 percent of respondents reported that secondhand smoke had drifted into their apartments in the past year. Households with members of vulnerable populations, such as children or individuals with chronic conditions, are more likely to report smoke drifting from adjacent units. Four out of five respondents--including more than half of those who self-reported currently smoking--supported a smoke-free policy in common areas and/or individual units.

A descriptive report of end-of-life care practices occurring in two neonatal intensive care units.

BACKGROUND: In Canada and other developed countries, the majority of neonatal deaths occur in tertiary neonatal intensive care units. Most deaths occur following the withdrawal of life-sustaining treatments. AIM: To explore neonatal death events and end-of-life care practices in two tertiary neonatal intensive care settings. DESIGN: A structured, retrospective, cohort study. SETTING/PARTICIPANTS: All infants who died under tertiary neonatal intensive care from January 2009 to December 2013 in a regional Canadian neonatal program. Deaths occurring outside the neonatal intensive care unit in delivery rooms, hospital wards, or family homes were not included. Overall, 227 infant deaths were identified. RESULTS: The most common reasons for admission included prematurity (53.7%), prematurity with congenital anomaly/syndrome (20.3%), term congenital anomaly (11.5%), and hypoxic ischemic encephalopathy (12.3%). The median age at death was 7 days. Death tended to follow a decision to withdraw life-sustaining treatment with anticipated poor developmental outcome or perceived quality of life, or in the context of a moribund dying infant. Time to death after withdrawal of life-sustaining treatment was uncommonly a protracted event but did vary widely. Most dying infants were held by family members in the neonatal intensive care unit or in a parent room off cardiorespiratory monitors. Analgesic and sedative medications were variably given and not associated with a hastening of death. CONCLUSION: Variability exists in end-of-life care practices such as provision of analgesic and sedative medications. Other practices such as discontinuation of cardiorespiratory monitors and use of parent rooms are more uniform. More research is needed to understand variation in neonatal end-of-life care.

Televised medical talk shows--what they recommend and the evidence to support their recommendations: a prospective observational study.

OBJECTIVE: To determine the quality of health recommendations and claims made on popular medical talk shows. DESIGN: Prospective observational study. SETTING: Mainstream television media. SOURCES: Internationally syndicated medical television talk shows that air daily (The Dr Oz Show and The Doctors). INTERVENTIONS: Investigators randomly selected 40 episodes of each of The Dr Oz Show and The Doctors from early 2013 and identified and evaluated all recommendations made on each program. A group of experienced evidence reviewers independently searched for, and evaluated as a team, evidence to support 80 randomly selected recommendations from each show. MAIN OUTCOMES MEASURES: Percentage of recommendations that are supported by evidence as determined by a team of experienced evidence reviewers. Secondary outcomes included topics discussed, the number of recommendations made on the shows, and the types and details of recommendations that were made. RESULTS: We could find at least a case study or better evidence to support 54% (95% confidence interval 47% to 62%) of the 160 recommendations (80 from each show). For recommendations in The Dr Oz Show, evidence supported 46%, contradicted 15%, and was not found for 39%. For recommendations in The Doctors, evidence supported 63%, contradicted 14%, and was not found for 24%. Believable or somewhat believable evidence supported 33% of the recommendations on The Dr Oz Show and 53% on The Doctors. On average, The Dr Oz Show had 12 recommendations per episode and The Doctors 11. The most common recommendation category on The Dr Oz Show was dietary advice (39%) and on The Doctors was to consult a healthcare provider (18%). A specific benefit was described for 43% and 41% of the recommendations made on the shows respectively. The magnitude of benefit was described for 17% of the recommendations on The Dr Oz Show and 11% on The Doctors. Disclosure of potential conflicts of interest accompanied 0.4% of recommendations. CONCLUSIONS: Recommendations made on medical talk shows often lack adequate information on specific benefits or the magnitude of the effects of these benefits. Approximately half of the recommendations have either no evidence or are contradicted by the best available evidence. Potential conflicts of interest are rarely addressed. The public should be skeptical about recommendations made on medical talk shows. Additional details of methods used and changes made to study protocol.

Variability in APOE genotype status in human-derived cell lines: a cause for concern in cell culture studies?

Although cell culture studies have provided landmark discoveries in the basic and applied life sciences, it is often under-appreciated that cells grown in culture are prone to generating artifacts. Here, we introduce the genotype status (exemplified by apolipoprotein E) of human-derived cells as a further important parameter that requires attention in cell culture experiments. Epidemiological and clinical studies indicate that variations from the main apolipoprotein E3/E3 genotype might alter the risk of developing chronic diseases, especially neurodegeneration, cardiovascular disease, and cancer. Whereas the apolipoprotein E allele distribution in human populations is well characterized, the apolipoprotein E genotype of human-derived cell lines is only rarely considered in interpreting cell culture data. However, we find that primary and immortalized human cell lines show substantial variation in their apolipoprotein E genotype status. We argue that the apolipoprotein E genotype status and corresponding gene expression level of human-derived cell lines should be considered to better avoid (or at least account for) inconsistencies in cell culture studies when different cell lines of the same tissue or organ are used and before extrapolating cell culture data to human physiology in health and disease.

Sex differences in adult cerebral venous sinus thrombosis: a 10-year experience.

BACKGROUND: Sex differences in the risk factors, presentation and outcome of cerebral venous sinus thrombosis (CVST) are poorly defined, despite a discrepant prevalence between males and females. The proportion of patients on hormonal therapy who develop CVST varies widely. We describe the clinical features, risk factors and outcome by sex and by hormone-related risk factors among a large cohort of patients. METHODS: We reviewed records of 108 consecutive patients with CVST at a tertiary hospital in Calgary between 1999 and 2009. Descriptive statistics were used for between group comparisons (men, women with hormone-related risk factors and women without hormone-related risk factors). RESULTS: Females made up 62% of patients, half of whom were on systemic hormonal therapy. Men and women without hormonal risk factors were older at onset. Oral contraceptive use was the major risk factor in women (45%) while concurrent mastoiditis was the most common predisposing factor in men (27%). Complications were frequent and overall mortality was 6%. Persisting deficits at discharge were more common in men (54% vs. 35% and 32%, p=0.036). There was a trend for women with hormone-related risk factors to have less residual focal neurologic deficit than the other groups (5% vs. 15% and 17%, p=0.051). CONCLUSIONS: There are differences between sexes in the presentation, risk factors and outcome of patients with CVST.

Current challenges of behavior change talk for medical professionals and trainees.

OBJECTIVE: To explore medical professionals' and trainees' experiences and views of behavior change talk in various health care settings to develop current understanding of the challenges that underlie this phenomenon. METHODS: Qualitative, semi-structured interviews were conducted with medical professionals and trainees (n=29). Grounded theory principles informed sampling, data collection and analysis. To achieve maximum variance, participants with different levels of experience were purposively sampled from a range of primary and secondary care settings. Analysis was iterative, involving a constant comparative approach allowing emergent ideas to be tested in subsequent interviews until thematic saturation was reached. RESULTS: Three emergent themes described reasons for not engaging in behavior change talk with patients: (1) 'personal challenges'; (2) 'somebody else's responsibility' and (3) 'prioritizing the doctor-patient relationship'. CONCLUSION: Despite increasingly being recognized as a core aspect of medical practice and education, medical professionals and trainees remain unprepared to discuss health-related behavior change with patients and unclear of their roles within contemporary health care. PRACTICE IMPLICATIONS: Formal training in theory-based behavior change techniques is likely to help empower doctors and mitigate many of the barriers found, particularly in relation to socially and emotionally uncomfortable topics that are perceived to threaten the doctor-patient relationship.