Cardiovascular adaptations supporting human exercise-heat acclimation

AbstractThis review examines the cardiovascular adaptations along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses during exercise-heat acclimation. The cardiovascular system is well recognized as an important contributor to exercise-heat acclimation that acts to minimize physiological strain, reduce the risk of serious heat illness and better sustain exercise capacity. The upright posture adopted by humans during most physical activities and the large skin surface area contribute to the circulatory and blood pressure regulation challenge of simultaneously supporting skeletal muscle blood flow and dissipating heat via increased skin blood flow and sweat secretion during exercise-heat stress. Although it was traditionally held that cardiac output increased during exercise-heat stress to primarily support elevated skin blood flow requirements, recent evidence suggests that temperature-sensitive mechanisms may also mediate an elevation in skeletal muscle blood flow. The cardiovascular adaptations supporting this challenge include an increase in total body water, plasma volume expansion, better sustainment and/or elevation of stroke volume, reduction in heart rate, improvement in ventricular filling and myocardial efficiency, and enhanced skin blood flow and sweating responses. The magnitude of these adaptations is variable and dependent on several factors such as exercise intensity, duration of exposure, frequency and total number of exposures, as well as the environmental conditions (i.e. dry or humid heat) in which acclimation occurs

Validation of an ingestible temperature data logging and telemetry system during exercise in the heat

Aim: Intestinal temperature telemetry systems are promising monitoring and research tools in athletes. However, the additional equipment that must be carried to continuously record temperature data limits their use to training. The purpose of this study was to assess the validity and reliability of a new gastrointestinal temperature data logging and telemetry system (e-Celsius™) during water bath experimentation and exercise trials. Materials and Methods: Temperature readings of 23 pairs of e-Celsius (T(eC)) and VitalSense (T(VS)) ingestible capsules were compared to rectal thermistor responses (T(rec)) at 35, 38.5 and 42°C in a water bath. Devices were also assessed in vivo during steady-state cycling (n = 11) and intermittent running (n = 11) in hot conditions. Results: The water bath experiment showed T(VS) and T(eC) under-reported T(rec) (P<0.001). This underestimation of T(rec) also occurred during both cycling (mean bias vs T(VS): 0.21°C, ICC: 0.84, 95% CI: 0.66–0.91; mean bias vs. T(eC): 0.44°C, ICC: 0.68, 95% CI: 0.07–0.86, P<0.05) and running trials (mean bias vs. T(VS): 0.15°C, ICC: 0.92, 95% CI: 0.83–0.96; mean bias vs. T(eC): 0.25, ICC: 0.86, 95% CI: 0.61–0.94, P<0.05). However, calibrating the devices attenuated this difference during cycling and eliminated it during running. During recovery following cycling exercise, T(eC) and T(VS) were significantly lower than T(rec) despite calibration (P<0.01). Conclusion: These results indicate that both T(eC) and T(VS) under-report T(rec) during steady-state and intermittent exercise in the heat, with T(eC) predicting T(rec) with the least accuracy of the telemetry devices. It is therefore recommended to calibrate these devices at multiple temperatures prior to use

A systematic review and meta-analysis of the effect of dispatcher-assisted CPR on outcomes from sudden cardiac arrest in adults and children

Background: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) has been reported in individual studies to significantly increase the rate of bystander CPR and survival from cardiac arrest. Methods: We undertook a systematic review and meta-analysis to evaluate the impact of DA-CPR programs on key clinical outcomes following out-of-hospital cardiac arrest. We searched the PubMED, EMBASE, CINAHL, ERIC and Cochrane Central Register of Controlled Trials databases from inception until July 2018. Eligible studies compared systems with and without dispatcher-assisted CPR programs. The results of included studies were classified into 3 categories for the purposes of more accurate analysis: comparison of outcomes in systems with DA-CPR programs, case-based comparison of DA-CPR to bystander CPR, and case-based comparisons of DA-CPR to no CPR before EMS arrival. The GRADE system was used to assess certainty of evidence at an outcome level. We used random-effects models to produce summary effect sizes across all outcomes. Results: Of 5531 citations screened, 33 studies were eligible for inclusion. All included studies were observational. Evidence certainty across all outcomes was assessed as low or very low. In system-level and patient-level comparisons, the provision of DA-CPR compared with no DA-CPR was consistently associated with improved outcome across all analyses. Comparison of DA-CPR to bystander CPR produced conflicting results. Findings were consistent across sensitivity analyses and the pediatric sub-group. Conclusion: These results support the recommendation that dispatchers provide CPR instructions to callers for adults and children with suspected OHCA. Review registration: PROSPERO- CRD42018091427

A translational signature for nucleosome positioning in vivo

In vivo nucleosomes often occupy well-defined preferred positions on genomic DNA. An important question is to what extent these preferred positions are directly encoded by the DNA sequence itself. We derive here from in vivo positions, accurately mapped by partial micrococcal nuclease digestion, a translational positioning signal that identifies the approximate midpoint of DNA bound by a histone octamer. This midpoint is, on average, highly A/T rich (∼73%) and, in particular, the dinucleotide TpA occurs preferentially at this and other outward-facing minor grooves. We conclude that in this set of sequences the sequence code for DNA bending and nucleosome positioning differs from the other described sets and we suggest that the enrichment of AT-containing dinucleotides at the centre is required for local untwisting. We show that this signature is preferentially associated with nucleosomes flanking promoter regions and suggest that it contributes to the establishment of gene-specific nucleosome arrays

Hubs with Network Motifs Organize Modularity Dynamically in the Protein-Protein Interaction Network of Yeast

BACKGROUND: It has been recognized that modular organization pervades biological complexity. Based on network analysis, 'party hubs' and 'date hubs' were proposed to understand the basic principle of module organization of biomolecular networks. However, recent study on hubs has suggested that there is no clear evidence for coexistence of 'party hubs' and 'date hubs'. Thus, an open question has been raised as to whether or not 'party hubs' and 'date hubs' truly exist in yeast interactome. METHODOLOGY: In contrast to previous studies focusing on the partners of a hub or the individual proteins around the hub, our work aims to study the network motifs of a hub or interactions among individual proteins including the hub and its neighbors. Depending on the relationship between a hub's network motifs and protein complexes, we define two new types of hubs, 'motif party hubs' and 'motif date hubs', which have the same characteristics as the original 'party hubs' and 'date hubs' respectively. The network motifs of these two types of hubs display significantly different features in spatial distribution (or cellular localizations), co-expression in microarray data, controlling topological structure of network, and organizing modularity. CONCLUSION: By virtue of network motifs, we basically solved the open question about 'party hubs' and 'date hubs' which was raised by previous studies. Specifically, at the level of network motifs instead of individual proteins, we found two types of hubs, motif party hubs (mPHs) and motif date hubs (mDHs), whose network motifs display distinct characteristics on biological functions. In addition, in this paper we studied network motifs from a different viewpoint. That is, we show that a network motif should not be merely considered as an interaction pattern but be considered as an essential function unit in organizing modules of networks

Identifying Hubs in Protein Interaction Networks

In spite of the scale-free degree distribution that characterizes most protein interaction networks (PINs), it is common to define an ad hoc degree scale that defines "hub" proteins having special topological and functional significance. This raises the concern that some conclusions on the functional significance of proteins based on network properties may not be robust.In this paper we present three objective methods to define hub proteins in PINs: one is a purely topological method and two others are based on gene expression and function. By applying these methods to four distinct PINs, we examine the extent of agreement among these methods and implications of these results on network construction.We find that the methods agree well for networks that contain a balance between error-free and unbiased interactions, indicating that the hub concept is meaningful for such networks

2017 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary

The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 paediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have pri-oritised and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question. (C) 2017 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Diagnosis of out-of-hospital cardiac arrest by Emergency Medical Dispatch : a diagnostic systematic review

Introduction Cardiac arrest is a time-sensitive condition requiring urgent intervention. Prompt and accurate recognition of cardiac arrest by emergency medical dispatchers at the time of the emergency call is a critical early step in cardiac arrest management allowing for initiation of dispatcher-assisted bystander CPR and appropriate and timely emergency response. The overall accuracy of dispatchers in recognizing cardiac arrest is not known. It is also not known if there are specific call characteristics that impact the ability to recognize cardiac arrest. Methods We performed a systematic review to examine dispatcher recognition of cardiac arrest as well as to identify call characteristics that may affect their ability to recognize cardiac arrest at the time of emergency call. We searched electronic databases for terms related to “emergency medical dispatcher”, “cardiac arrest’, and “diagnosis,” among others, with a focus on studies that allowed for calculating diagnostic test characteristics (e.g. sensitivity and specificity). The review was consistent with Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method for evidence evaluation. Results We screened 2520 article titles, resulting in 47 studies included in this review. There was significant heterogeneity between studies with a high risk of bias in 18 of the 47 which precluded performing meta-analyses. The reported sensitivities for cardiac arrest recognition ranged from 0.46 to 0.98 whereas specificities ranged from 0.32 to 1.00. There were no obvious differences in diagnostic accuracy between different dispatching criteria/algorithms or with the level of education of dispatchers. Conclusion The sensitivity and specificity of cardiac arrest recognition at the time of emergency call varied across dispatch centres and did not appear to differ by dispatch algorithm/criteria used or education of the dispatcher, although comparisons were hampered by heterogeneity across studies. Future efforts should focus on ways to improve sensitivity of cardiac arrest recognition to optimize patient care and ensure appropriate and timely resource utilizatio