Dominique Gagnon

Strategies intended to address vaccine hesitancy: Review of published reviews

When faced with vaccine hesitancy, public health authorities are looking for effective strategies to address this issue. In this paper, the findings of 15 published literature reviews or meta-analysis that have examined the effectiveness of different interventions to reduce vaccine hesitancy and/or to enhance vaccine acceptance are presented and discussed. From the literature, there is no strong evidence to recommend any specific intervention to address vaccine hesitancy/refusal. The reviewed studies included interventions with diverse content and approaches that were implemented in different settings and targeted various populations. Few interventions were directly targeted to vaccine hesitant individuals. Given the paucity of information on effective strategies to address vaccine hesitancy, when interventions are implemented, planning a rigorous evaluation of their impact on vaccine hesitancy/vaccine acceptance will be essential.

Mapping vaccine hesitancy—Country-specific characteristics of a global phenomenon

Highlights • Vaccine hesitancy is a global problem that is complex and multilayered. Vaccine hesitancy is context, time, place and vaccine specific.• Interviews with immunization managers were conducted to determine the breadth and perceived drivers of vaccine hesitancy at the countries’ level.• Our study results, not unexpectedly, revealed a wide variation in the reported basis for vaccine hesitancy across countries.

Understanding Vaccine Hesitancy in Canada: Results of a Consultation Study by the Canadian Immunization Research Network

“Vaccine hesitancy” is a concept now frequently used in vaccination discourse. The increased popularity of this concept in both academic and public health circles is challenging previously held perspectives that individual vaccination attitudes and behaviours are a simple dichotomy of accept or reject. A consultation study was designed to assess the opinions of experts and health professionals concerning the definition, scope, and causes of vaccine hesitancy in Canada. We sent online surveys to two panels (1- vaccination experts and 2- front-line vaccine providers). Two questionnaires were completed by each panel, with data from the first questionnaire informing the development of questions for the second. Our participants defined vaccine hesitancy as an attitude (doubts, concerns) as well as a behaviour (refusing some / many vaccines, delaying vaccination). Our findings also indicate that both vaccine experts and front-line vaccine providers have the perception that vaccine rates have been declining and consider vaccine hesitancy an important issue to address in Canada. Diffusion of negative information online and lack of knowledge about vaccines were identified as the key causes of vaccine hesitancy by the participants. A common understanding of vaccine hesitancy among researchers, public health experts, policymakers and health care providers will better guide interventions that can more effectively address vaccine hesitancy within Canada.

The Effects of Cold Exposure on Leukocytes, Hormones and Cytokines during Acute Exercise in Humans

The purpose of the study was to examine the effects of exercise on total leukocyte count and subsets, as well as hormone and cytokine responses in a thermoneutral and cold environment, with and without an individualized pre-cooling protocol inducing low-intensity shivering. Nine healthy young men participated in six experimental trials wearing shorts and t-shirts. Participants exercised for 60 min on a treadmill at low (LOW: 50% of peak VO2) and moderate (MOD: 70% VO2peak) exercise intensities in a climatic chamber set at 22°C (NT), and in 0°C (COLD) with and without a pre-exercise low-intensity shivering protocol (SHIV). Core and skin temperature, heart rate and oxygen consumption were collected continuously. Blood samples were collected before and at the end of exercise to assess endocrine and immunological changes. Core temperature in NT was greater than COLD and SHIV by 0.4±0.2°C whereas skin temperature in NT was also greater than COLD and SHIV by 8.5±1.4°C and 9.3±2.5°C respectively in MOD. Total testosterone, adenocorticotropin and cortisol were greater in NT vs. COLD and SHIV in MOD. Norepinephrine was greater in NT vs. other conditions across intensities. Interleukin-2, IL-5, IL-7, IL-10, IL-17, IFN-γ, Rantes, Eotaxin, IP-10, MIP-1β, MCP-1, VEGF, PDGF, and G-CSF were elevated in NT vs. COLD and/or SHIV. Furthermore, IFN-γ, MIP-1β, MCP-1, IL-10, VEGF, and PDGF demonstrate greater concentrations in SHIV vs. COLD, mainly in the MOD condition. This study demonstrated that exercising in the cold can diminish the exercise-induced systemic inflammatory response seen in a thermoneutral environment. Nonetheless, prolonged cooling inducing shivering thermogenesis prior to exercise, may induce an immuno-stimulatory response following moderate intensity exercise. Performing exercise in cold environments can be a useful strategy in partially inhibiting the acute systemic inflammatory response from exercise but oppositely, additional body cooling may reverse this benefit.

Core cooling and thermal responses during whole-head, facial, and dorsal immersion in 17°C water.

This study isolated the effects of dorsal, facial, and whole-head immersion in 17 degrees C water on peripheral vasoconstriction and the rate of body core cooling. Seven male subjects were studied in thermoneutral air (approximately 28 degrees C). On 3 separate days, they lay prone or supine on a bed with their heads inserted through the side of an adjustable immersion tank. Following 10 min of baseline measurements, the water level was raised such that the water immersed the dorsum, face, or whole head, with the immersion period lasting 60 min. During the first 30 min, the core (esophageal) cooling rate increased from dorsum (0.29 ± 0.2 degrees C h-1) to face (0.47 ± 0.1 degrees C h-1) to whole head (0.69 ± 0.2 degrees C h(-1)) (p < 0.001); cooling rates were similar during the final 30 min (mean, 0.16 ± 0.1 degrees C h(-1)). During the first 30 min, fingertip blood flow (laser Doppler flux as percent of baseline) decreased faster in whole-head immersion (114 ± 52% h(-1)) than in either facial (51 ± 47% h-1) or dorsal (41 ± 55% h(-1)) immersion (p < 0.03); rates of flow decrease were similar during minutes 30 to 60 (mean, 22.5 ± 19% h(-1)). Total head heat loss over 60 min was significantly different between whole-head (120.5 ± 13 kJ), facial (86.8 ± 17 kJ), and dorsal (46.0 ± 11 kJ) immersion (p < 0.001). The rate of core cooling, relative to head heat loss, was similar in all conditions (mean, 0.0037 ± 0.001 degree C kJ(-1)). Although the whole head elicited a higher rate of vasoconstriction, the face did not elicit more vasoconstriction than the dorsum. Rather, the progressive increase in core cooling from dorsal to facial to whole-head immersion simply correlates with increased heat loss.

Fuel selection during short-term submaximal treadmill exercise in the cold is not affected by pre-exercise low-intensity shivering

Exercise and shivering rely on different metabolic pathways and consequently, fuel selection. The present study examined the effects of a pre-exercise low-intensity shivering protocol on fuel selection during submaximal exercise in a cold environment. Nine male subjects exercised 4 times for 60 min at 50% (LOW) or 70% (MOD) of their peak oxygen consumption on a motorized treadmill in a climatic chamber set at 0 °C with (SHIV) and without (CON) a pre-exercise cooling protocol, inducing low-intensity shivering. Thermal, cardiorespiratory and metabolic responses were measured every 15 min whereas blood samples were collected every 30 min to assess serum nonesterified fatty acids (NEFA), glycerol, glucose, β-hydroxybutyrate (BHB) and plasma catecholamine concentrations. Rectal and skin temperatures were lower in the SHIV condition, within LOW and MOD conditions, during the first 45 min of exercise. Norepinephrine (NE) concentration was greater in SHIV vs. CON within LOW (1.39 ± 0.17 vs. 0.98 ± 0.17 ng·mL(-1)) and MOD (1.50 ± 0.20 vs. 1.01 ± 0.09 ng·mL(-1)), whereas NEFA, glycerol and BHB were greater in SHIV vs. CON (1060 ± 49 vs. 898 ± 78 μmol·L(-1); 0.27 ± 0.02 vs. 0.22 ± 0.03 mmol·L(-1); 0.39 ± 0.06 vs. 0.27 ± 0.04 mmol·L(-1), respectively) within MOD only. No changes were observed in fat or carbohydrate oxidation between SHIV and CON during exercise. Despite increases in NE, NEFA, glycerol and BHB from pre-exercise low-intensity shivering, fuel selection during short-term submaximal exercise in the cold was unaltered.

Cold exposure enhances fat utilization but not non-esterified fatty acids, glycerol or catecholamines availability during submaximal walking and running

Cold exposure modulates the use of carbohydrates (CHOs) and fat during exercise. This phenomenon has mostly been observed in controlled cycling studies, but not during walking and running when core temperature and oxygen consumption are controlled, as both may alter energy metabolism. This study aimed at examining energy substrate availability and utilization during walking and running in the cold when core temperature and oxygen consumption are maintained. Ten lightly clothed male subjects walked or ran for 60-min, at 50% and 70% of maximal oxygen consumption, respectively, in a climatic chamber set at 0°C or 22°C. Thermal, cardiovascular, and oxidative responses were measured every 15-min during exercise. Blood samples for serum non-esterified fatty acids (NEFAs), glycerol, glucose, beta-hydroxybutyrate (BHB), plasma catecholamines, and serum lipids were collected immediately prior, and at 30- and 60-min of exercise. Skin temperature strongly decreased while core temperature did not change during cold trials. Heart rate (HR) was also lower in cold trials. A rise in fat utilization in the cold was seen through lower respiratory quotient (RQ) (−0.03 ± 0.02), greater fat oxidation (+0.14 ± 0.13 g · min−1) and contribution of fat to total energy expenditure (+1.62 ± 1.99 kcal · min−1). No differences from cold exposure were observed in blood parameters. During submaximal walking and running, a greater reliance on derived fat sources occurs in the cold, despite the absence of concurrent alterations in NEFAs, glycerol, or catecholamine concentrations. This disparity may suggest a greater reliance on intra-muscular energy sources such as triglycerides during both walking and running.

Cardiovascular and ventilatory responses to dorsal, facial, and whole-head water immersion in eupnea.

OBJECTIVE Facial cooling can regulate reflexes of the dive response whereas further body cooling generally induces the cold-shock response. We examined the cardiovascular and ventilatory parameters of these responses during 3-min immersions of the head dorsum, face, and whole head in 17 degrees C water while breathing was maintained. METHODS From a horizontal position, the head was inserted into a temperature controlled immersion tank in which the water level could be changed rapidly. On four occasions, either the head dorsum, face or whole head (prone and supine) were exposed to water. RESULTS Mean decrease in heart rate (14%) and increases in systolic (9%) and diastolic (5%) blood pressures were seen during immersion. Relative mean finger skin blood flow had an early transient decrease (31%) for 90 s and then returned to baseline values. A strong transient increase was seen in minute ventilation (92%) at 20 s of immersion via tidal volume (85%). There were no consistent differences between the head dorsum, face, and whole head for all variables in response to immersion. CONCLUSIONS The cold-shock response (increased minute ventilation and tidal volume) predominated over the dive response in the initial moments of immersion only. The order of emergence of these responses provides further recommendation to avoid head submersion upon cold water entry. It is important to protect the face, with a facemask, and the head dorsum, with an insulative hood, in cold water.

Irisin – ‘New Kid on the Block in energy regulation’?

Irisin was originally identified as a muscle-derived glycosylated polypeptide in January 2012 by Bostr€ om and his colleagues (Bostr€ om et al. 2012). It is well established that physical exercise stimulates the transcriptional coactivator PGC-1a in skeletal muscles, resulting in health benefits such as reduction in obesity and insulin resistance. Bostr€ om and his colleagues hypothesized that PGC-1a stimulates expression of genes involved in obesity prevention and insulin resistance. To investigate this, they conditioned adipocyte cultures via PGC-1a-expressing myocytes, which increased the expressions of several genes (Prdm16, UCP1, Cidea) inducing a thermogenic expression programme in adipose cells (browning). The group then identified the genes responsible for the secreted products as PGC-1a target genes using gene expression array: IL-15, FNDC5 (fibronectin type III domaincontaining protein 5), VEGF-b, LRG1 and TIMP4. FNDC5, a transmembrane protein expressed in skeletal muscle and other tissues, stimulated the thermogenic response in adipose tissue, while IL-15 and VEGF-b had no effect. Bostr€ om and his colleagues demonstrated that a novel polypeptide, which they named irisin, was cleaved from FNDC5. The authors suggested that irisin as a novel myokine might mediate – at least in part – the beneficial effects of exercise on diabetes, obesity and related metabolic disorders. These findings raised great interest of the role of irisin in healthy and diseased populations. Bostr€ om et al. (2012) observed that plasma irisin as measured by immunoblotting (antibody against recombinant FNDC5) rose significantly after 3 weeks of exercise in mice and after 10 weeks of endurance training in eight healthy elderly men. Western blot analysis of human plasma showed that the na€ıve irisin is glycosylated with a band at 32 kDa, while the deglycosylated irisin has a band at 20 kDa. Other groups have reported variable sizes for deglycosylated irisin (29.5 kDa, Schumacher et al. 2013; 24 kDa, Lee et al. 2014a). Circulating irisin is thus glycosylated and appears to be a dimer (Schumacher et al. 2013). Timmons et al. (2012) studied FNDC5 expression in muscle after endurance cycling or resistance training in two cohorts with younger subjects. Despite increases in mitochondrial gene expressions and physical fitness, no changes were seen between FNDC5 expression and insulin sensitivity or glucose levels. Age difference might explain why Timmons et al. did not observe any changes in FNDC5 expression in response to exercise compared with Bostr€ om et al. Furthermore, Huh et al. (2012) exposed young healthy subjects to intermittent sprint running sessions. Plasma immunoreactive irisin was significantly elevated at the 1st week but not at the 8th week. Pekkala et al. (2013) measured skeletal muscle FNDC5 and plasma irisin immunoreactivity in men performing several types of exercises including: (i) 1 h low-intensity aerobic exercise, (ii) a resistance bout and (iii) a 21-week endurance training performed biweekly either alone or with resistance training. The only significant finding was the increase in FNDC5 mRNA expression after a resistance bout in young, but not old men. Changes in PGC-1a or serum irisin did not consistently correlate with changes in FNDC5. Raschke et al. (2013) observed that endurance training or strength training for 10–11 weeks had no effects on muscle FNDC5 gene expression and that contractions of primary human myotubes by electrical stimuli in vitro led to increased PGC-1a expression, but the expression of FNDC5 remained unchanged. They also found that FNDC5 (Abnova, Taipei City, Taiwan) and irisin (Phoenix Pharmaceuticals, Inc, Burlingame, CA, USA) failed to induce the thermogenic gene expression profile in isolated human subcutaneous adipocytes. Furthermore, FNDC5 is expressed in and secreted from adipocytes (Roca-Rivada et al. 2013). Indeed, it has been shown that plasma irisin levels in healthy subjects correlated positively with BMI (Stengel et al. 2013) and biceps circumference (Huh et al. 2012). However, Moreno-Navarrete et al. (2013) reported a negative correlation of irisin levels with obesity and insulin resistance, but their irisin levels were extremely high (2.15 lg/mL in lean compared with 1.65 lg/mL in obese subjects). Roca-Rivada et al. (2013) studied ex vivo expression of FNDC5 in rat adipose tissues’ explants. They found an increased FNDC5/irisin secretion from adipocytes of animals exposed to wheel exercise. The authors speculated that app. 72% of the circulating FNDC5/irisin comes from the muscle as a ‘myokine’, the remaining from the adipose tissue as an adipokine. The function of the ‘adipokine’ irisin is unknown. Irisin immunoassays (ELISA/EIA) from several companies have been used in studies dealing with associations of plasma/serum irisin with exercise, obesity, T2D and other diseases, and great variations

Clothing buoyancy and underwater horizontal swim distance after exiting a submersed vehicle simulator

BACKGROUND Winter road workers, who drive heavy vehicles over ice-covered waterways, are at risk for ice failure, vehicle submersion, and subsequent drowning in frigid water. Although some jurisdictions require these workers to wear flotation clothing, there are concerns that, following an underwater exit in fast-moving water, increased clothing buoyancy may reduce ability to swim against the current to safely return to the ice opening. METHODS Using a simulator in a swimming pool (3.7 m deep, 28 degrees C), 11 volunteers (5 women) were submersed 8 times each to test the effects from both an Upright and an Inverted position of a normal nonflotation winter jacket (Control), a flotation Jacket, a flotation Overall, and a personal inflatable vest which was inflated (Inflated Vest) on underwater horizontal swim distance. Subjects also rated exit difficulty and impedance, psychological stress, and thermal comfort. RESULTS Compared to Control, Jacket, and Overall, the Inflated Vest generally increased exit difficulty, escape impedance, and psychological stress, while greatly decreasing the ability to swim horizontally underwater before reaching the surface (Control, 6.1 m; Jacket, 5.0 m; Overall, 3.4 m; and Inflated Vest only 1.4 m). Swim distance with the Overall was also significantly shorter than Control, but not Jacket. DISCUSSION Flotation clothing (either Jackets or Overalls) is recommended for vehicle travel on ice because they do not impede underwater exit from a vehicle and allow significant horizontal underwater swim distance. An inflatable vest is not recommended because inappropriate premature inflation could increase exit impedance and decreased underwater swim distance.