Concept: Ibn al-Nafis
A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography.
During development, endothelial cells (EC) display tissue-specific attributes that are unique to each vascular bed, as well as generic signaling mechanisms that are broadly applied to create a patent circulatory system. We have previously utilized human embryonic stem cells (hESC) to generate tissue-specific EC sub-types (Rafii et al., 2013) and identify pathways that govern growth and trans-differentiation potential of hESC-derived ECs (James et al., 2010). Here, we elucidate a novel Notch-dependent mechanism that induces endothelial to mesenchymal transition (EndMT) in confluent monolayer cultures of hESC-derived ECs. We demonstrate density-dependent induction of EndMT that can be rescued by the Notch signaling inhibitor DAPT and identify a positive feedback signaling mechanism in hESC-ECs whereby trans-activation of Notch by DLL4 ligand induces elevated expression and surface presentation of DLL4. Increased Notch activation in confluent hESC-EC monolayer cultures induces areas of EndMT containing transitional cells that are marked by increased Jagged1 expression and reduced Notch signal integration. Jagged1 loss of function in monolayer hESC-ECs induces accelerated feedback stimulation of Notch signaling, increased expression of cell-autonomous, cis-inhibitory DLL4, and EndMT. These data elucidate a novel interplay of Notch ligands in modulating pathway activation during both expansion and EndMT of hESC-derived ECs.
Slow breathing practices have been adopted in the modern world across the globe due to their claimed health benefits. This has piqued the interest of researchers and clinicians who have initiated investigations into the physiological (and psychological) effects of slow breathing techniques and attempted to uncover the underlying mechanisms. The aim of this article is to provide a comprehensive overview of normal respiratory physiology and the documented physiological effects of slow breathing techniques according to research in healthy humans. The review focuses on the physiological implications to the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems, with particular focus on diaphragm activity, ventilation efficiency, haemodynamics, heart rate variability, cardiorespiratory coupling, respiratory sinus arrhythmia and sympathovagal balance. The review ends with a brief discussion of the potential clinical implications of slow breathing techniques. This is a topic that warrants further research, understanding and discussion.
Systemic vascular pressure in vertebrates is regulated by a range of factors: one key element of control is peripheral resistance in tissue capillary beds. Many aspects of the relationship between central control of vascular flow and peripheral resistance are unclear. An important example of this is the relationship between hypoxic response in individual tissues, and the effect that response has on systemic cardiovascular adaptation to oxygen deprivation. We show here how hypoxic response via the HIF transcription factors in one large vascular bed, that underlying the skin, influences cardiovascular response to hypoxia in mice. We show that the response of the skin to hypoxia feeds back on a wide range of cardiovascular parameters, including heart rate, arterial pressures, and body temperature. These data represent the first demonstration of a dynamic role for oxygen sensing in a peripheral tissue directly modifying cardiovascular response to the challenge of hypoxia.
High-intensity interval training (HIT), in a variety of forms, is today one of the most effective means of improving cardiorespiratory and metabolic function and, in turn, the physical performance of athletes. HIT involves repeated short-to-long bouts of rather high-intensity exercise interspersed with recovery periods. For team and racquet sport players, the inclusion of sprints and all-out efforts into HIT programmes has also been shown to be an effective practice. It is believed that an optimal stimulus to elicit both maximal cardiovascular and peripheral adaptations is one where athletes spend at least several minutes per session in their ‘red zone,’ which generally means reaching at least 90 % of their maximal oxygen uptake ([Formula: see text]O2max). While use of HIT is not the only approach to improve physiological parameters and performance, there has been a growth in interest by the sport science community for characterizing training protocols that allow athletes to maintain long periods of time above 90 % of [Formula: see text]O2max (T@[Formula: see text]O2max). In addition to T@[Formula: see text]O2max, other physiological variables should also be considered to fully characterize the training stimulus when programming HIT, including cardiovascular work, anaerobic glycolytic energy contribution and acute neuromuscular load and musculoskeletal strain. Prescription for HIT consists of the manipulation of up to nine variables, which include the work interval intensity and duration, relief interval intensity and duration, exercise modality, number of repetitions, number of series, as well as the between-series recovery duration and intensity. The manipulation of any of these variables can affect the acute physiological responses to HIT. This article is Part I of a subsequent II-part review and will discuss the different aspects of HIT programming, from work/relief interval manipulation to the selection of exercise mode, using different examples of training cycles from different sports, with continued reference to T@[Formula: see text]O2max and cardiovascular responses. Additional programming and periodization considerations will also be discussed with respect to other variables such as anaerobic glycolytic system contribution (as inferred from blood lactate accumulation), neuromuscular load and musculoskeletal strain (Part II).
High-intensity exercise is associated with mechanical and/or metabolic stresses that lead to reduced performance capacity of skeletal muscle, soreness and inflammation. Cold-water immersion and other forms of cryotherapy are commonly used following a high-intensity bout of exercise to speed recovery. Cryotherapy in its various forms has been used in this capacity for a number of years; however, the mechanisms underlying its recovery effects post-exercise remain elusive. The fundamental change induced by cold therapy is a reduction in tissue temperature, which subsequently exerts local effects on blood flow, cell swelling and metabolism and neural conductance velocity. Systemically, cold therapy causes core temperature reduction and cardiovascular and endocrine changes. A major hindrance to defining guidelines for best practice for the use of the various forms of cryotherapy is an incongruity between mechanistic studies investigating these physiological changes induced by cold and applied studies investigating the functional effects of cold for recovery from high-intensity exercise. When possible, studies investigating the functional recovery effects of cold therapy for recovery from exercise should concomitantly measure intramuscular temperature and relevant temperature-dependent physiological changes induced by this type of recovery strategy. This review will discuss the acute physiological changes induced by various cryotherapy modalities that may affect recovery in the hours to days (<5 days) that follow high-intensity exercise.
To demonstrate proof-of-principle measurement for physiologic change within an active myofascial trigger point (MTrP) undergoing trigger point release (ischemic compression).
The intrinsic advantages of microcapsules with regard to nanocapsules as intravenous drug carrier systems are still not fully exploited. Especially, in clinical situations where a long-term drug release within the vascular system is desired, if large amounts of drug have to be administered or if capillary leakage occurs, long-circulating microparticles may display a superior alternative to nanoparticles. Here, microcapsules were synthesised and parameters such as in vitro tendency of agglomeration, protein adsorption and in vivo performance were investigated. Biocompatible poly(ethylene glycol) (PEG)-coated poly(DL-lactide-co-glycolide) (PLGA) as wall material, solid and perfluorodecalin (PFD)-filled PEG-PLGA microcapsules (1.5 µm diameter) were manufactured by using a modified solvent evaporation method with either 1% poly(vinyl alcohol) (PVA) or 1.5% cholate as emulsifying agents. Compared to microcapsules manufactured with cholate, the protein adsorption (albumin and IgG) was clearly decreased and agglomeration of capsules was prevented, when PVA was used. The intravenous administration of these microcapsules, both solid and PFD-filled, in rats was successful and exhibited a circulatory half-life of about 1 h. Our data clearly demonstrate that PEG-PLGA microcapsules, manufactured by using PVA, are suitable biocompatible, long-circulating drug carriers, applicable for intravenous administration.
OBJECTIVE: Compromised perfusion of the capillary bed can lead to organ failure and mortality in sepsis. We have reported that intravenous injection of ascorbate inhibits platelet adhesion and plugging in septic capillaries. In the present study we hypothesized that ascorbate reduces aggregation of platelets and their surface expression of P-selectin (a key adhesion molecule) in mice. METHODS: Platelets were isolated from control mice and subjected to agents known to be released into the bloodstream during sepsis (thrombin, ADP or U46619, thromboxane A2 analog). Platelet aggregation was analysed by aggregometry and P-selectin expression by flow cytometry. RESULTS: Platelet-activating agents increased aggregation and P-selectin expression. Ascorbate inhibited these increases. This inhibitory effect was NOS-independent (LNAME had no effect). In contrast to the platelet-activating agents, direct stimuli lipopolysaccharide, TNFα or plasma from septic mice did not increase aggregation/expression, a finding consistent with the literature. The results suggest a complex mechanism of platelet aggregation and P-selectin expression in sepsis, where generation of platelet-activating stimuli is required first, before platelet aggregation and adhesion in capillaries occur. CONCLUSION: The ability of ascorbate to reduce platelet aggregation and P-selectin expression could be an important mechanism by which ascorbate inhibits capillary plugging in sepsis. © 2013 John Wiley & Sons Ltd.
Supplementation with nitrate (NO₃(-))-rich beetroot juice has been shown to improve exercise performance and cardiovascular (CV) responses, due to an increased nitric oxide (NO) availability. However, it is unclear whether these benefits are greater in older adults who have an age-related decrease in NO and higher risk of disease. This systematic review examines 12 randomised, crossover, control trials, investigating food-based NO₃(-) supplementation in older adults and its potential benefits on physiological and cognitive performances, and CV, cerebrovascular and metabolic health. Four studies found improvements in physiological performance (time to exhaustion) following dietary NO₃(-) supplementation in older adults. Benefits on cognitive performance were unclear. Six studies reported improvements in CV health (blood pressure and blood flow), while six found no improvement. One study showed improvements in cerebrovascular health and two found no improvement in metabolic health. The current literature indicates positive effects of dietary NO₃(-) supplementation in older adults on physiological performance, with some evidence indicating benefits on cardiovascular and cerebrovascular health. Effects on cognitive performance were mixed and studies on metabolic health indicated no benefit. However, there has been limited research conducted on the effects of dietary NO₃(-) supplementation in older adults, thus, further study, utilising a randomised, double-blind, control trial design, is warranted.