The current study examined the adaptive response to both endurance (END) and sprint interval training (SIT) in a group of twenty-one recreationally active adults. All participants completed three ...weeks (four days/ week) of both END (30 minutes at ~65% VO2peak work rate (WR) and SIT (eight, 20-second intervals at ~170% VO2peak WR separated by 10 seconds of active rest) following a randomized crossover study design with a three-month washout period between training interventions. While a main effect of training was observed for VO2peak, lactate threshold, and submaximal heart rate (HR), considerable variability was observed in the individual responses to both END and SIT. No significant positive relationships were observed between END and SIT for individual changes in any variable. Non-responses were determined using two times the typical error (TE) of measurement for VO2peak (0.107 L/min), lactate threshold (15.7 W), and submaximal HR (10.7bpm). Non-responders in VO2peak, lactate threshold, and submaximal HR were observed following both END and SIT, however, the individual patterns of response differed following END and SIT. Interestingly, all individuals responded in at least one variable when exposed to both END and SIT. These results suggest that the individual response to exercise training is highly variable following different training protocols and that the incidence of non-response to exercise training may be reduced by changing the training stimulus for non-responders to three weeks of END or SIT.
The opioid crisis is a growing public health emergency and increasing resources are being directed towards overdose education. Simulation has emerged as a novel strategy for training overdose ...response, yet little is known about training non-clinicians in bystander resuscitation. Understanding the perspectives of individuals who are likely to experience or witness opioid overdose is critical to ensure that emergency response is effective. The Surviving Opioid Overdose with Naloxone Education and Resuscitation (SOONER) study evaluates the effectiveness of a novel naloxone education and distribution tool among people who are non-clinicians and likely to witness opioid overdose. Participants’ resuscitation skills are evaluated using a realistic overdose simulation as the primary outcome of the trial. The purpose of our study is to describe the experience of participants with the simulation process in the SOONER study. We employed a semi-structured debriefing interview and a follow up qualitative interview to understand the experience of participants with simulation. A qualitative content analysis was performed using data from 21 participants who participated in the SOONER study. Our qualitative analysis identified 5 themes and 17 subthemes which described the experience of participants within the simulation process. These themes included realism, valuing practical experience, improving self-efficacy, gaining new perspective and bidirectional learning. Our analysis found that simulation was a positive and empowering experience for participants in the SOONER trial, most of whom are marginalized in society. Our study supports the notion that expanding simulation-based education to non-clinicians may offer an acceptable and effective way of supplementing current opioid overdose education strategies. Increasing the accessibility of simulation-based education may represent a paradigm shift whereby simulation is transformed from a primarily academic practice into a patient-based community resource.
This study investigated whether VO
peak is reproducible across repeated tests before (PRE) and after (POST) training, and whether variability across tests impacts how individual responses are ...classified following 3 weeks of aerobic exercise training (cycle ergometry). Data from 45 young healthy adults (age: 20·1 ± 0·9 years; VO
peak, 42·0 ± 6·7 ml·min
) from two previously published studies were utilized in the current analysis. Non-responders were classified as individuals who failed to demonstrate an increase or decrease in VO
peak that was greater than 2·0 times the typical error of measurement (107 ml·min
) away from zero, while responders and adverse responders were above and below this cut-off, respectively. VO
peak tests at PRE (three total) and POST (three total) were highly reproducible (PRE and POST average and single measures ICCs: range 0·938-0·992), with low coefficients of variation (PRE:4·9 ± 3·1%, POST: 4·8 ± 2·7%). However, a potential learning effect was observed in the VO
peak tests prior to training, as the initial pretraining test was significantly lower than the third (p = 0·010, PRE 1: 2 946 ± 924 ml·min
, PRE 3: 3 042 ± 919 ml·min
). This resulted in fewer individuals classified as adverse responders for Test 3 compared to any combination of tests that included Test 1, suggesting that a single ramp test at baseline may not be sufficient to accurately classify the VO
peak response in young recreationally active individuals. Thus, it is our recommendation that the initial VO
peak test be used as a familiarization visit and not included for analysis.
Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impact of disease, the molecular basis for protection remains unclear. ...Streptococcus pneumoniae is a major cause of bacterial pneumonia, which is prevalent in regions of zinc deficiency. We report that dietary zinc levels dictate the outcome of S. pneumoniae infection in a murine model. Dietary zinc restriction impacts murine tissue zinc levels with distribution post-infection altered, and S. pneumoniae virulence and infection enhanced. Although the activation and infiltration of murine phagocytic cells was not affected by zinc restriction, their efficacy of bacterial control was compromised. S. pneumoniae was shown to be highly sensitive to zinc intoxication, with this process impaired in zinc restricted mice and isolated phagocytic cells. Collectively, these data show how dietary zinc deficiency increases sensitivity to S. pneumoniae infection while revealing a role for zinc as a component of host antimicrobial defences.
E‐cigarettes are perceived as harmless; however, evidence of their safety is lacking. New data suggests E‐cigarettes discharge a range of compounds capable of physiological damage to users. We ...previously established that cigarette smoke caused defective alveolar macrophage phagocytosis. The present study compared the effect E‐cigarette of components; E‐liquid flavors, nicotine, vegetable glycerine, and propylene glycol on phagocytosis, proinflammatory cytokine secretion, and phagocytic recognition molecule expression using differentiated THP‐1 macrophages. Similar to CSE, phagocytosis of NTHi bacteria was significantly decreased by E‐liquid flavoring (11.65–15.75%) versus control (27.01%). Nicotine also decreased phagocytosis (15.26%). E‐liquid, nicotine, and E‐liquid+ nicotine reduced phagocytic recognition molecules; SR‐A1 and TLR‐2. IL‐8 secretion increased with flavor and nicotine, while TNFα, IL‐1β, IL‐6, MIP‐1α, MIP‐1β, and MCP‐1 decreased after exposure to most flavors and nicotine. PG, VG, or PG:VG mix also induced a decrease in MIP‐1α and MIP‐1β. We conclude that E‐cigarettes can cause macrophage phagocytic dysfunction, expression of phagocytic recognition receptors and cytokine secretion pathways. As such, E‐cigarettes should be treated with caution by users, especially those who are nonsmokers.
E‐cigarettes are marketed as a safer alternative to tobacco cigarettes, however the number of nonsmokers using E‐cigarettes is steadily rising, especially amongst youth. We investigated the effect of E‐cigarettes on healthy cells. We discovered that E‐cigarettes altered the phagocyotsis of pathogenic bacteria by macrophages via reduced expression of surface recognition receptors.
Haemophilus influenzae is a commensal of the human upper respiratory tract that can infect diverse host niches due, at least in part, to its ability to withstand both endogenous and host-mediated ...oxidative stresses. Here, we show that hfeA, a gene previously linked to iron import, is essential for H. influenzae manganese recruitment via the HfeBCD transporter. Structural analyses show that metal binding in HfeA uses a unique mechanism that involves substantial rotation of the C-terminal lobe of the protein. Disruption of hfeA reduced H. influenzae manganese acquisition and was associated with decreased growth under aerobic conditions, impaired manganese-superoxide dismutase activity, reduced survival in macrophages, and changes in biofilm production in the presence of superoxide. Collectively, this work shows that HfeA contributes to H. influenzae manganese acquisition and virulence attributes. High conservation of the hfeABCD permease in Haemophilus species suggests that it may serve similar roles in other pathogenic Pasteurellaceae.
Five 1-benzazepine heterocycles were synthesized by utilizing transition-metal-catalyzed processes in key bond-forming steps. exo-Methylene and methyl substituents were introduced at position 5, as ...well as a unit of unsaturation between positions 3 and 4, with benzoyl or benzyl N-substituents. Solution- and solid-state structures were examined, using dynamic NMR spectroscopy and X-ray crystallography, corroborated by molecular mechanics calculations. Greater amide distortion is associated with a more stable ground-state structure, which is in turn more reluctant to undergo conformational changes.
Partially and fully reduced forms of benzo-fused eight- to ten-membered nitrogen heterocycles (1-benzazecines, 1-benzazonines and 1-benzazecines) have been prepared. Conformational features, ...transannular distances and dynamic behavior were studied using X-ray crystallography and VT NMR spectroscopy. The amide moiety in the nine-membered benzazonine ring 5b favors N-pyramidization, whereas the ten-membered benzazecine 5c adopts an amide twist. Molecular mechanics calculations reveals a correlation between the amide twist (τ) and ring stability. The dynamic behavior of the heterocycles in solution were also found to be dependent on the extent and nature of the amide distortion. We thus conclude that ring strain of these medium-sized heterocyclic rings is relieved through amide distortion, which leads to a more stable structure.
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