A summer heat wave decreases the immunocompetence of the mesograzer, Idotea baltica

Extreme events associated with global change will impose increasing stress on coastal organisms. How strong biological interactions such as the host–parasite arms-race are modulated by environmental change is largely unknown. The immune system of invertebrates, in particular phagocytosis and phenoloxidase activity response are key defence mechanisms against parasites, yet they may be sensitive to environmental perturbations. We here simulated an extreme event that mimicked the European heat wave in 2003 to investigate the effect of environmental change on the immunocompetence of the mesograzer Idotea baltica. Unlike earlier studies, our experiment aimed at simulation of the natural situation as closely as possible by using long acclimation, a slow increase in temperature and a natural community setting including the animals’ providence with natural food sources (Zostera marina and Fucus vesiculosus). Our results demonstrate that a simulated heat wave results in decreased immunocompetence of the mesograzer Idotea baltica, in particular a drop of phagocytosis by 50%. This suggests that global change has the potential to significantly affect host–parasite interactions

Circadian clock mechanism driving mammalian photoperiodism.

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-basis for photoperiodic synchronization. Here, light-dark cycles entrain a circadian rhythm of photosensitivity, and the expression of summer or winter biology depends on whether light coincides with the phase of high photosensitivity. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that coincidence timing takes place in the pars tuberalis of the pituitary, through a melatonin-dependent flip-flop switch between circadian transcriptional activation and repression. Long photoperiods produce short night-time melatonin signals, leading to induction of the circadian transcription factor BMAL2, in turn triggering summer biology through the eyes absent / thyrotrophin (EYA3 / TSH) pathway. Conversely, short photoperiods produce long melatonin signals, inducing circadian repressors including DEC1, in turn suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock interactions with pituitary epigenetic pathways form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates

Navigating the Healthcare Conundrum: Leadership Perspective from a Premier Healthcare Organization in Loma Linda’s Blue Zone

Laren D Tan,1 Anthony A Hilliard,2 Ricardo L Peverini,3 Robert D Martin,4 Tamara L Thomas,5 Trevor G Wright,6 Lyndon C Edwards,6 Angela M Lalas,6 Helen M Staples-Evans,6 Barbara J Sharp,7 Stella L Ahn-Kim,7 Kent A Hansen,6 Richard H Hart8 1Department of Medicine, Pulmonary, Critical Care, Hyperbaric and Sleep Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA; 2Department of Medicine, Cardiology, Loma Linda University School of Medicine, Loma Linda, CA, USA; 3Department of Pediatrics, Neonatology, Loma Linda University School of Medicine, Loma Linda, CA, USA; 4Department of Anesthesia, Loma Linda University School of Medicine, Loma Linda, CA, USA; 5Department of Emergency Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA; 6Loma Linda University Health, Loma Linda, CA, USA; 7Loma Linda University School of Medicine, Loma Linda, CA, USA; 8Department of Preventive Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USACorrespondence: Laren D Tan, Email [email protected]: Navigating the healthcare conundrum in the Blue Zone of Loma Linda, California, requires understanding the unique factors that make this region stand out in terms of health and longevity. But more important is understanding the healthcare system sustaining the Blue Zone in Loma Linda, California. In an era marked by soaring healthcare costs and diminishing reimbursement rates, hospitals and physicians face an unprecedented challenge: providing excellent patient care while maintaining financial sustainability. This leadership perspective publication paper delves into the multifaceted struggles encountered by healthcare and hospital leaders, exploring the root causes, implications, and potential solutions for this complex issue. As we examine the evolving healthcare landscape, we aim to shed light on the critical need for innovative approaches to sustain the future of healthcare excellence in one of the five original Blue Zones.Keywords: blue zone, Loma Linda, healthcare cost, leadership healthcare, longevity, Californi

Provider perspectives on multilevel barriers to HPV vaccination

Understanding physician recommendation practices for HPV vaccination is a crucial step to developing interventions that can increase high quality recommendations and improve vaccination acceptance. Florida physicians (n = 340) completed a survey assessing recommendation strategies, specifically strength, consistency, and presentation. Physicians were also asked to provide suggestions for improving HPV vaccination in Florida. Responses were dichotomized for each outcome: strength (i.e., strongly recommend vs. other), consistently recommend (i.e., always recommend vs. other), and recommendation presentation (i.e., presented in the same manner as mandatory vaccines for adolescents vs. other). Bivariate logistic regression was conducted to determine the association between physician/practice characteristics and each outcome. Variables significant (p < .05) in bivariate analyses were included in multivariable logistic regression analyses. Vaccines for Children (VFC) provider status (OR = 2.62, 95% CI = 1.23–5.59 [strong]; OR = 2.84, 95% CI = 1.26–6.39 [consistent]) and not limiting the number of vaccines during a visit (OR = .283, 95% = CI .111-.722 [strong]; OR = .210, 95% = CI .066-.673 [consistent]) were significantly associated with strong and consistent recommendation. Reminders from the healthcare team were associated with consistency (OR = 2.26, 95% CI = 1.23–4.16) and EMR-based reminders were associated with presentation (OR = 2.00, 95% CI = 1.11–3.61). Multinomial logistic regression analysis examined factors associated with level of engagement in recommendation strategies. Multinomial regression indicated VFC providers (OR = 12.61, 95% CI = 1.89–82.20), and those receiving EMR-based reminders (OR = 4.02, 95% = CI 1.28–12.63), among others, were more likely to engage in all 3 types of recommendation practices. Physician suggestions for improving HPV vaccination rates included improving parent/patient/provider education and reducing vaccine costs. Future interventions should emphasize key components of delivering effective HPV vaccine recommendations, include information about insurance coverage, and improve provider awareness of VFC benefits

Ziram activates mitogen-activated protein kinases and decreases cytolytic protein levels in human natural killer cells

Human natural killer (NK) cells are central in immune defense with their ability to lyse tumor cells and virally infected cells. Tumor formation and viral infection may increase if NK cytotoxic function is disrupted. Ziram (zinc dithiocarbamate) is used as an accelerating agent in the production of latex and to protect various fruits and vegetables from fungal infection. Previously, we have shown that exposure to ziram inhibits NK lytic function. Butyltin environmental contaminants, which also inhibit NK lytic function, cause rapid activations of mitogen-activated protein kinases (MAPKs) and decreases in expression of the cytolytic proteins granzyme B and perforin (after 24 h) in exposed NK cells. MAPKs are important regulators of the lytic response of NK cells, and spurious activation of these enzymes by contaminants would leave the NK cells unable to respond to appropriate targets. This study examined the effects of ziram exposures on MAPKs (p44/42, p38, and c-jun-N-terminal kinase) and on levels of cytolytic proteins. Ten-minute to 6-h exposures of NK cells to ziram caused activation of MAPKs, p44/42, and p38. Exposure to ziram for 24 h caused a decrease in granzyme B and perforin levels. MAPK inhibitors were able to prevent these ziram-induced decreases in granzyme B and perforin. These results suggest that ziram-induced MAPK activation is at least in part responsible for decreased cytolytic function in ziram-exposed NK cells. Furthermore, the results indicate that these changes are in common with other environmental contaminants that have been shown to decrease NK lytic function