Light affects heart rate's 24-h rhythmicity in intensive care unit patients: An observational study

Muurlink, OT ORCiD: 0000-0002-8251-9521Background: Intensive care unit (ICU) patients experience two affronts to normal 24-h rhythms: largely internal events such as medication and external factors such as light, noise and nursing interventions. Aims and objectives: We investigated the impact of light variance within an ICU on 24-h rhythmicity of three key physiological parameters: heart rate (HR), mean arterial blood pressure (MAP) and body temperature (BT) in this patient population. Design: Patients were assigned to beds either in the ‘light’ or ‘dark’ side within a single ICU. An actigraph continuously recorded light intensity for a 24–72-h period. Methods: Measurements of HR, MAP and BT were recorded every 30 min. Results: HR, MAP and BT did not follow 24-h rhythmicity in all patients. Higher light exposure in the Light Side of the ICU (122·3 versus 50·6 lx) was related to higher HR (89·4 versus 79·8 bpm), which may translate to clinically relevant outcomes in a larger sample. Duration of stay, the one clinical outcome measured in this study, showed no significant variation between the groups (p = 0·147). Conclusions: ICU patients are exposed to varying light intensities depending on bed positioning relative to natural sunlight, affecting the 24-h rhythm of HR. Larger, well-controlled studies also investigating the effect of relevant light intensity are indicated. Relevance to clinical practice: Light is a variable that can be manipulated in the constrained environment of an ICU, thus offering an avenue for relatively unobtrusive interventions. © 2019 British Association of Critical Care Nurse

Antitumor reactive T-cell responses are enhanced in vivo by DAMP prothymosin alpha and Its C-terminal decapeptide

Prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreactivity of cancer patients’ leukocytes. Previously, we showed that proTα and proTα(100–109) act as danger-associated molecular patterns (DAMPs), ligate Toll-like receptor-4, signal through TRIF-and MyD88-dependent pathways, promote the maturation of dendritic cells and elicit T-helper type 1 (Th1) immune responses in vitro, leading to the optimal priming of tumor antigen-reactive T-cell functions. Herein, we assessed their activity in a preclinical melanoma model. Immunocompetent mice bearing B16.F1 tumors were treated with two cycles of proTα or proTα(100–109) together with a B16.F1-derived peptide vaccine. Coadministration of proTα or proTα(100–109) and the peptide vaccine suppressed melanoma-cell proliferation, as evidenced by reduced tumor-growth rates. Higher melanoma infiltration by CD3+ T cells was observed, whereas ex vivo analysis of mouse total spleen cells verified the in vivo induction of melanoma-reactive cytotoxic responses. Additionally, increased levels of proinflammatory and Th1-type cytokines were detected in mouse serum. We propose that, in the presence of tumor antigens, DAMPs proTα and proTα(100–109) induce Th1-biased immune responses in vivo. Their adjuvant ability to orchestrate antitumor immunoreactivities can eventually be exploited therapeutically in humans. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Clusterin overexpression in mice exacerbates diabetic phenotypes but suppresses tumor progression in a mouse melanoma model.

Clusterin (CLU) is an ATP-independent small heat shock protein-like chaperone, which functions both intra- and extra-cellularly. Consequently, it has been functionally involved in several physiological (including aging), as well as in pathological conditions and most age-related diseases, e.g., cancer, neurodegeneration, and metabolic syndrome. To address CLU function at an in vivo model we established CLU transgenic (Tg) mice bearing ubiquitous or pancreas-targeted CLU overexpression (OE). Our downstream analyses in established Tg lines showed that ubiquitous or pancreas-targeted CLU OE in mice affected antioxidant, proteostatic and metabolic pathways. Targeted OE of CLU in the pancreas, which also resulted in CLU upregulation in the liver likely via systemic effects, increased basal glucose levels in the circulation and exacerbated diabetic phenotypes. Furthermore, by establishing a syngeneic melanoma mouse tumor model we found that ubiquitous CLU OE suppressed melanoma cells growth, indicating a likely tumor suppressor function in early phases of tumorigenesis. Our observations provide in vivo evidence corroborating the notion that CLU is a potential modulator of metabolic and/or proteostatic pathways playing an important role in diabetes and tumorigenesis

Antitumor reactive T-cell responses are enhanced in vivo by DAMP prothymosin alpha and its C-terminal decapeptide

Prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreactivity of cancer patients’ leukocytes. Previously, we showed that proTα and proTα(100–109) act as danger-associated molecular patterns (DAMPs), ligate Toll-like receptor-4, signal through TRIF- and MyD88-dependent pathways, promote the maturation of dendritic cells and elicit T-helper type 1 (Th1) immune responses in vitro, leading to the optimal priming of tumor antigen-reactive T-cell functions. Herein, we assessed their activity in a preclinical melanoma model. Immunocompetent mice bearing B16.F1 tumors were treated with two cycles of proTα or proTα(100–109) together with a B16.F1-derived peptide vaccine. Coadministration of proTα or proTα(100–109) and the peptide vaccine suppressed melanoma-cell proliferation, as evidenced by reduced tumor-growth rates. Higher melanoma infiltration by CD3+ T cells was observed, whereas ex vivo analysis of mouse total spleen cells verified the in vivo induction of melanoma-reactive cytotoxic responses. Additionally, increased levels of proinflammatory and Th1-type cytokines were detected in mouse serum. We propose that, in the presence of tumor antigens, DAMPs proTα and proTα(100–109) induce Th1-biased immune responses in vivo. Their adjuvant ability to orchestrate antitumor immunoreactivities can eventually be exploited therapeutically in humans