The physiological response to stress and an individual’s subjective perception of stress are two systems vital to enabling adaptive responses to dangerous stimuli and maintaining individual well-being. When the body’s biological stress response and psychological interpretations of stress become misaligned, referred to as a low stress-heart rate coherence, detriments to health can occur (Sommerfeldt et al., 2019). Objective measures of physical stress, such as interleukin-6 and C-reactive protein, pro-inflammatory biomarkers of stress, and heart rate were analyzed in association with self-reported stress, measures of well-being, anxiety, and depression in a pool of Midlife participants from the United States. The present study utilized this data to replicate analyses performed by the original paper, “Individual Differences in the Association Between Subjective Stress and Heart Rate Are Related to Psychological and Physical Well-Being”. Preliminary findings from this effort indicate inconsistencies between standard statistical values due to missing data, however still illustrate a significant association between stress-heart rate coherence and wellbeing. We additionally attempted to explore the data further by running all statistical analyses for just white participants, hypothesizing that greater stress-heart rate coherence might be limited to this overrepresented demographic. We could not confirm nor deny the prediction, as we did not have access to full data to run analyses with minority data. In any case, all analyses yielded positive associations between individual well-being and stress heart-rate coherence, although further studies with more representative samples are imperative in understanding the generalizability and mechanisms for coherence.

Pilot programs have been implemented in cities across the U.S. to address the first- and last- mile problem with door-to-door shared microtransit, ridehailing companies, and shared-ride operators with dynamic pick-up locations. The City of Rancho Cordova and Lyft partnered to launch one such pilot in the form of a discount-based door-to-door (D2D) coupon program named “Free ＄5 to Ride”. The program offers ＄5 credits to Lyft riders who start or end their trips at one of four Sacramento Regional Transit District (SacRT) light rail stations. The program was designed to reduce rider dependence on personal vehicles and increase the overall convenience of transit use in the region. UC Davis researchers conducted an evaluation of the “Free ＄5 to Ride” program during its operational period of May 2019 through June 2021. Researchers developed a participant survey and used survey data along with participant trip data, ridership data for the SacRT light rail, and ridership data for the Rancho CordoVan shuttle service to characterize the outcomes of the pilot program. The evaluation shows that the coupon program was generally well-received. Participation levels increased dramatically by early 2020, and while trip activity dropped at the onset of the COVID-19 pandemic, program activity remained fairly constant through the end of the program. Researchers encountered survey sampling limitations due to ridehailing customer engagement policies, suggesting that future evaluations of similar programs would benefit from increased data access, or modified policies allowing operators to conduct more extensive outreach in support of these studies.

Small- and intermediate-conductance Ca²⁺-activated potassium (K_Ca2.x and K_Ca3.1, also called SK and IK) channels are activated exclusively by a Ca²⁺-calmodulin gating mechanism. Wild-type K_Ca2.3 channels have a Ca²⁺ EC₅₀ value of ∼0.3 μM, while the apparent Ca²⁺ sensitivity of wild-type K_Ca3.1 channels is ∼0.27 μM. Heterozygous genetic mutations of K_Ca2.3 channels have been associated with Zimmermann-Laband syndrome and idiopathic noncirrhotic portal hypertension, while K_Ca3.1 channel mutations were reported in hereditary xerocytosis patients. K_Ca2.3_S436C and K_Ca2.3_V450L channels with mutations in the S₄₅A/S₄₅B helices exhibited hypersensitivity to Ca²⁺. The corresponding mutations in K_Ca3.1 channels also elevated the apparent Ca²⁺ sensitivity. K_Ca3.1_S314P, K_Ca3.1_A322V and K_Ca3.1_R352H channels with mutations in the HA/HB helices are hypersensitive to Ca²⁺, whereas K_Ca2.3 channels with the equivalent mutations are not. The different effects of the equivalent mutations in the HA/HB helices on the apparent Ca²⁺ sensitivity of K_Ca2.3 and K_Ca3.1 channels may imply distinct modulation of the two channel subtypes by the HA/HB helices. AP14145 reduced the apparent Ca²⁺ sensitivity of the hypersensitive mutant K_Ca2.3 channels, suggesting the potential therapeutic usefulness of negative gating modulators.

A series of modified N-cyclohexyl-2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methylpyrimidin-4-amine (CyPPA) analogues were synthesized by replacing the cyclohexane moiety with different 4-substituted cyclohexane rings, tyrosine analogues, or mono- and dihalophenyl rings and were subsequently studied for their potentiation of K_Ca2 channel activity. Among the N-benzene-N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine derivatives, halogen decoration at positions 2 and 5 of benzene-substituted 4-pyrimidineamine in compound 2q conferred a ∼10-fold higher potency, while halogen substitution at positions 3 and 4 of benzene-substituted 4-pyrimidineamine in compound 2o conferred a ∼7-fold higher potency on potentiating K_Ca2.2a channels, compared to that of the parent template CyPPA. Both compounds retained the K_Ca2.2a/K_Ca2.3 subtype selectivity. Based on the initial evaluation, compounds 2o and 2q were selected for testing in an electrophysiological model of spinocerebellar ataxia type 2 (SCA2). Both compounds were able to normalize the abnormal firing of Purkinje cells in cerebellar slices from SCA2 mice, suggesting the potential therapeutic usefulness of these compounds for treating symptoms of ataxia.

Many genetic and environmental factors increase susceptibility to cognitive impairment (CI), and the gut microbiome is increasingly implicated. However, the identity of gut microbes associated with CI risk, their effects on CI, and their mechanisms remain unclear. Here, we show that a carbohydrate-restricted (ketogenic) diet potentiates CI induced by intermittent hypoxia in mice and alters the gut microbiota. Depleting the microbiome reduces CI, whereas transplantation of the risk-associated microbiome or monocolonization with Bilophila wadsworthia confers CI in mice fed a standard diet. B. wadsworthia and the risk-associated microbiome disrupt hippocampal synaptic plasticity, neurogenesis, and gene expression. The CI is associated with microbiome-dependent increases in intestinal interferon-gamma (IFNg)-producing Th1 cells. Inhibiting Th1 cell development abrogates the adverse effects of both B. wadsworthia and environmental risk factors on CI. Together, these findings identify select gut bacteria that contribute to environmental risk for CI in mice by promoting inflammation and hippocampal dysfunction.

Introduction

Supportive care models considering inclusivity and community services to improve integrated care for cancer survivors are limited. In this case study, we described the implementation of a multidisciplinary care model employing routine distress screening and embedded integrated care pathways to integrate care across disciplines and care sectors, while remaining inclusive of the multi-ethnic and multilingual population in Singapore. We reported implementation outcomes after 18 months of implementation.

Description

We reviewed the model's process indicators from September 2019 to February 2021 at the largest public ambulatory cancer centre. Outcomes assessed included penetration, fidelity to screening protocol, and feasibility in three aspects - inclusiveness of different ethnic and language groups, responsiveness to survivors reporting high distress, and types of community service referrals.

Discussion/conclusion

We elucidated opportunities to promote access to community services and inclusivity. Integration of community services from tertiary settings should be systematic through mutually beneficial educational and outreach initiatives, complemented by their inclusion in integrated care pathways to encourage systematic referrals and care coordination. A hybrid approach to service delivery is crucial in ensuring inclusivity while providing flexibility towards external changes such as the COVID-19 pandemic. Future work should explore using telehealth to bolster inclusiveness and advance community care integration.

Purpose

The Accessible Cancer Care to Enable Support for Cancer Survivors (ACCESS) program adopts a multidisciplinary supportive care model with routine distress screening to triage newly diagnosed cancer survivors for additional support on the basis of distress levels. This study aimed to evaluate the clinical impact of ACCESS over 1 year.

Methods

We performed cluster random assignment at the oncologist level in a 1:1 ratio to receive ACCESS or usual care. Participants 21 years and older, newly diagnosed with breast or gynecologic cancer, and receiving care at National Cancer Centre Singapore were included. Outcomes assessed every 3 months for 1 year included quality of life (QoL) (primary), functioning, physical and psychological symptom burden, and activity levels. Data were analyzed using mixed-effects models.

Results

Participants from 16 clusters (control = 90, intervention = 83) were analyzed. The ACCESS program did not significantly improve QoL (primary outcome). However, compared with usual care recipients, ACCESS recipients reported higher physical functioning (P = .017), role functioning (P = .001), and activity levels (P < .001) at 9 months and lower psychological distress (P = .025) at 12 months. ACCESS recipients screened with high distress had poorer QoL, lower role and social functioning, and higher physical symptom distress at 3 months but had comparable scores with ACCESS recipients without high distress after 12 months.

Conclusion

Compared with usual care, participation in the ACCESS program did not yield QoL improvement but showed earlier functioning recovery related to activities of daily living and reduced psychological distress. Routine distress screening is a promising mechanism to identify survivors with poorer health for more intensive supportive care.