A unifying model to estimate the effect of heat stress in the human innate immunity during physical activities

Abstract Public health is threatened by climate change and extreme temperature events worldwide. Differences in health predispositions, access to cooling infrastructure and occupation raises an issue of heat-related health inequality in those vulnerable and disadvantaged demographic groups. To address these issues, a comprehensive understanding of the effect of elevated body temperatures on human biological systems and overall health is urgently needed. In this paper we look at the inner workings of the human innate immunity under exposure to heat stress induced through exposure to environment and physical exertion. We couple two experimentally validated computational models: the innate immune system and thermal regulation of the human body. We first study the dynamics of critical indicators of innate immunity as a function of human core temperature. Next, we identify environmental and physical activity regimes that lead to core temperature levels that can potentially compromise the performance of the human innate immunity. Finally, to take into account the response of innate immunity to various intensities of physical activities, we utilise the dynamic core temperatures generated by a thermal regulation model. We compare the dynamics of all key players of the innate immunity for a variety of stresses like running a marathon, doing construction work, and leisure walking at speed of 4 km/h, all in the setting of a hot and humid tropical climate such as present in Singapore. We find that exposure to moderate heat stress leading to core temperatures within the mild febrile range (37, 38] \,^{\circ }\hbox {C} ∘ C , nudges the innate immune system into activation and improves the efficiency of its response. Overheating corresponding to core temperatures beyond 38 \,^{\circ }\hbox {C} ∘ C , however, has detrimental effects on the performance of the innate immune system, as it further induces inflammation, which causes a series of reactions that may lead to the non-resolution of the ongoing inflammation. Among the three physical activities considered in our simulated scenarios (marathon, construction work, and walking), marathon induces the highest level of inflammation that challenges the innate immune response with its resolution. Our study advances the current state of research towards understanding the implications of heat exposure for such an essential physiological system as the innate immunity. Although we find that among considered physical activities, a marathon of 2 h and 46 min induces the highest level of inflammation, it must be noted that construction work done on a daily basis under the hot and humid tropical climate, can produce a continuous level of inflammation triggering moieties stretched at a longer timeline beating the negative effects of running a marathon. Our study demonstrates that the performance of the innate immune system can be severely compromised by the exposure to heat stress and physical exertion. This poses significant risks to health especially to those with limited access to cooling infrastructures. This is due in part to having low income, or having to work on outdoor settings, which is the case for construction workers. These risks to public health should be addressed through individual and population-level measures via behavioural adaptation and provision of the cooling infrastructure in outdoor environments

RESULTS AND INTERPRETATION OF SOIL LOSS MEASUREMENTS FROM STEEP SLOPES IN THE PHILIPPINES

Abstract Measurements of runoff-event soil loss and one-minute rates of rainfall and runoff are reported for runoff plots installed on the tropical Philippine island of Leyte. Plots were either under traditional crops cultivated using farmer practices, or kept bare. Plots were of length 12 m and at slopes of 50% to 70%. Soil loss for the cultivated crop was 35 t ha -1 y -1 , and 63 t ha -1 y -1 for the bare soil plots. An erodibility parameter β calculated for bare-plot data exceeded the value 1 for lower stream power events, indicating enhancement of flow-driven erosion by other processes, such as rainfall impact. This conclusion held whether an original erosion model was employed, or a subsequent model development designed to acknowledge the special effects of very high sediment concentrations and shallow flows common at the site

Early and long-term outlook of percutaneous coronary intervention for bifurcation lesions in young patients

Coronary artery disease is most common in older patients, but may occur in younger subjects. The outlook of young patients after percutaneous coronary intervention (PCI) of challenging lesion subsets such as coronary bifurcations, is not established. We thus aimed to appraise the early and long-term results of PCI for bifurcations in young patients

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial.

Summary Background It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. Methods We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. Findings We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). Interpretation In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. Funding The Medicines Company and Terumo. © 2015 Elsevier Ltd

Supplemented Alkaline Phosphatase Supports the Immune Response in Patients Undergoing Cardiac Surgery: Clinical and Computational Evidence

Alkaline phosphatase (AP) is an enzyme that exhibits anti-inflammatory effects by dephosphorylating inflammation triggering moieties (ITMs) like bacterial lipopolysaccharides and extracellular nucleotides. AP administration aims to prevent and treat peri- and post-surgical ischemia reperfusion injury in cardiothoracic surgery patients. Recent studies reported that intravenous bolus administration and continuous infusion of AP in patients undergoing coronary artery bypass grafting with cardiac valve surgery induce an increased release of liver-type “tissue non-specific alkaline phosphatase” (TNAP) into the bloodstream. The release of liver-type TNAP into circulation could be the body's way of strengthening its defense against a massive ischemic insult. However, the underlying mechanism behind the induction of TNAP is still unclear. To obtain a deeper insight into the role of AP during surgery, we developed a mathematical model of systemic inflammation that clarifies the relation between supplemented AP and TNAP and describes a plausible induction mechanism of TNAP in patients undergoing cardiothoracic surgery. The model was validated against clinical data from patients treated with bovine Intestinal AP (bIAP treatment) or without AP (placebo treatment), in addition to standard care procedures. We performed additional in-silico experiments adding a secondary source of ITMs after surgery, as observed in some patients with complications, and predicted the response to different AP treatment regimens. Our results show a strong protective effect of supplemented AP for patients with complications. The model provides evidence of the existence of an induction mechanism of liver-type tissue non-specific alkaline phosphatase, triggered by the supplementation of AP in patients undergoing cardiac surgery. To the best of our knowledge this is the first time that a quantitative and validated numerical model of systemic inflammation under clinical treatment conditions is presented