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Chang, Herng-Yu Sucie, and Wayne Mitzner. "Sex differences in mouse models of asthma." Canadian Journal of Physiology and Pharmacology 85, no. 12 (December 2007): 1226–35. http://dx.doi.org/10.1139/y07-116.
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Differences in disease susceptibility and prognosis between men and women are known to occur in the incidence and development of neurodegenerative, cardiovascular, and immunological disorders. In the lung there are also sex-based differences in the incidence, prevalence, and pathogenesis of lung cancer, cystic fibrosis, COPD, and asthma. In the general population, sex-based differences in asthma have been shown by epidemiologic studies, but unfortunately these studies are not consistent in their conclusions. This variability in human epidemiological studies justifies the need for more focused studies of the effects of specific hormones. Such specific mechanistic studies can most easily be performed in animal models, and since mouse models have the potential for separating specific genetic factors from environmental and exogenous factors, this species has become increasingly important in the design, analysis, and interpretation of asthma research. This review will document the male and female differences in airway function of naïve and sensitized mouse models, as well as the great variability in the functional measurements of airway tone. Until the situation is better understood, this variability between males and females should be kept in mind when designing, analyzing, and interpreting studies of smooth muscle responses in animal models and human subjects.
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Kalidhindi, Rama Satyanarayana Raju, Niyati A. Borkar, Nilesh Sudhakar Ambhore, Christina M. Pabelick, Y. S. Prakash, and Venkatachalem Sathish. "Sex steroids skew ACE2 expression in human airway: a contributing factor to sex differences in COVID-19?" American Journal of Physiology-Lung Cellular and Molecular Physiology 319, no. 5 (November 1, 2020): L843—L847. http://dx.doi.org/10.1152/ajplung.00391.2020.
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The incidence, severity, and mortality of ongoing coronavirus infectious disease 19 (COVID-19) is greater in men compared with women, but the underlying factors contributing to this sex difference are still being explored. In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males versus females as a model, we explored the effect of estrogen versus testosterone in modulating the expression of angiotensin converting enzyme 2 (ACE2), a cell entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using confocal imaging, we found that ACE2 is expressed in human ASM. Furthermore, Western analysis of ASM cell lysates showed significantly lower ACE2 expression in females compared with males at baseline. In addition, ASM cells exposed to estrogen and testosterone for 24 h showed that testosterone significantly upregulates ACE2 expression in both males and females, whereas estrogen downregulates ACE2, albeit not significant compared with vehicle. These intrinsic and sex steroids induced differences may help explain sex differences in COVID-19.
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Dominelli, Paolo B., and Yannick Molgat-Seon. "Sex, gender and the pulmonary physiology of exercise." European Respiratory Review 31, no. 163 (January 12, 2022): 210074. http://dx.doi.org/10.1183/16000617.0074-2021.
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In this review, we detail how the pulmonary system's response to exercise is impacted by both sex and gender in healthy humans across the lifespan. First, the rationale for why sex and gender differences should be considered is explored, and then anatomical differences are highlighted, namely that females typically have smaller lungs and airways than males. Thereafter, we describe how these anatomical differences can impact functional aspects such as respiratory muscle energetics and activation, mechanical ventilatory constraints, diaphragm fatigue, and pulmonary gas exchange in healthy adults and children. Finally, we detail how gender can impact the pulmonary response to exercise.
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Kalidhindi, Rama Satyanarayana Raju, Nilesh Sudhakar Ambhore, Premanand Balraj, Taylor Schmidt, M. Nadeem Khan, and Venkatachalem Sathish. "Androgen receptor activation alleviates airway hyperresponsiveness, inflammation, and remodeling in a murine model of asthma." American Journal of Physiology-Lung Cellular and Molecular Physiology 320, no. 5 (May 1, 2021): L803—L818. http://dx.doi.org/10.1152/ajplung.00441.2020.
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Epidemiological studies demonstrate an apparent sex-based difference in the prevalence of asthma, with a higher risk in boys than girls, which is reversed postpuberty, where women become more prone to asthma than men, suggesting a plausible beneficial role for male hormones, especially androgens as a regulator of pathophysiology in asthmatic lungs. Using a murine model of asthma developed with mixed allergen (MA) challenge, we report a significant change in airway hyperresponsiveness (AHR), as demonstrated by increased thickness of epithelial and airway smooth muscle layers and collagen deposition, as well as Th2/Th17-biased inflammation in the airways of non-gonadectomized (non-GDX) and gonadectomized (GDX) male mice. Here, compared with non-GDX mice, MA-induced AHR and inflammatory changes were more prominent in GDX mice. Activation of androgen receptor (AR) using 5α-dihydrotestosterone (5α-DHT, AR agonist) resulted in decreased Th2/Th17 inflammation and remodeling-associated changes, resulting in improved lung function compared with MA alone challenged mice, especially in GDX mice. These changes were not observed with Flutamide (Flut, AR antagonist). Overall, we show that AR exerts a significant and beneficial role in asthma by regulating AHR and inflammation.
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Ford, Lincoln E. "Plasticity in airway smooth muscle: an update." Canadian Journal of Physiology and Pharmacology 83, no. 10 (October 1, 2005): 841–50. http://dx.doi.org/10.1139/y05-089.
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At a similar meeting 10 years ago, we proposed (i) that the long functional range of some smooth muscles is accommodated by plastic alterations that place more myofilaments in series at longer lengths, (ii) that this plasticity is facilitated by myosin filament evanescence, with filaments dissociating partially during relaxation and reforming upon activation, and (iii) that filament lengthening during the rise of activation would cause velocity to fall. Since that meeting, we have accumulated a substantial body of evidence to support these proposals, as follows: (i) muscles develop nearly the same force when adapted to a range of lengths that can vary by 3-fold; (ii) other physiological parameters including shortening velocity, maximum power, compliance, ATPase rate, and thick-filament mass increase by about 2/3 for a doubling of muscle length; (iii) thick-filament density increases substantially during the rise of activation; and (iv) velocity falls as force rises during the rise of tetanic force, and when correction is made for differences in activation, velocity and force vary exactly in inverse proportion. This review explains the rationale for the different experimental measurements and their interpretation.Key words: muscle activation, series-to-parallel transition, myofilaments, myosin.
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Card, Jeffrey W., James W. Voltz, Catherine D. Ferguson, Michelle A. Carey, Laura M. DeGraff, Shyamal D. Peddada, Daniel L. Morgan, and Darryl C. Zeldin. "Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulation." American Journal of Physiology-Lung Cellular and Molecular Physiology 292, no. 4 (April 2007): L908—L914. http://dx.doi.org/10.1152/ajplung.00407.2006.
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A sex disparity in airway responsiveness to cholinergic stimulation has been observed in laboratory mice in that males are considerably more responsive than females, but the basis for this difference is unclear. In this report, we demonstrate that male sex hormones promote murine airway responsiveness to cholinergic stimulation via vagus nerve-mediated reflex mechanisms. In tissue bath preparations, no sex-based differences were observed in the contractile responses of isolated tracheal and bronchial ring segments to carbachol, indicating that the mechanism(s) responsible for the in vivo sex difference is (are) absent ex vivo. Bilateral cervical vagotomy was found to abolish in vivo airway responsiveness to methacholine in male mice, whereas it did not alter the responses of females, suggesting a regulatory role for male sex hormones in promoting reflex airway constriction. To test this possibility, we next studied mice with altered circulating male sex hormone levels. Castrated male mice displayed airway responsiveness equivalent to that observed in intact females, whereas administration of exogenous testosterone to castrated males restored responsiveness, albeit not to the level observed in intact males. Administration of exogenous testosterone to intact female mice similarly enhanced responsiveness. Importantly, the promotive effects of exogenous testosterone in castrated male and intact female mice were absent when bilateral vagotomy was performed. Together, these data indicate that male sex hormones promote cholinergic airway responsiveness via a vagally mediated reflex mechanism that may be important in the regulation of airway tone in the normal and diseased lung.
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Kurti, Stephanie P., Sam R. Emerson, Joshua R. Smith, Sara K. Rosenkranz, Samantha A. Alexander, Garrett M. Lovoy, and Craig A. Harms. "Older women exhibit greater airway 8-isoprostane responses to strenuous exercise compared with older men and younger controls." Applied Physiology, Nutrition, and Metabolism 43, no. 5 (May 2018): 497–503. http://dx.doi.org/10.1139/apnm-2017-0565.
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Development of late-onset respiratory diseases is associated with elevated 8-isoprostane, a marker of oxidative stress, in the airways. However, sex differences exist in development of these diseases. Using an exhaustive exercise bout as a physiological stressor may elucidate whether there is a sex difference with aging in pre- to postexercise airway 8-isoprostane generation. The purpose of this study was to determine whether older women exhibit a greater airway 8-isoprostane response to exhaustive exercise compared with older men and younger controls. Thirty-six individuals completed the study (12 postmenopausal older women (OW) and 12 age-matched older men (OM), 65 ± 4 years of age; and 12 younger controls (YC), 21 ± 2 years of age). Baseline measurements included exhaled breath condensate (EBC) for assessment of airway 8-isoprostane and standard pulmonary function tests (PFTs) to assess forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow at 25%–75% of FVC. Subjects then performed a peak oxygen uptake test to exhaustion on a cycle ergometer. Immediately postexercise, PFTs and EBC were performed. The generation of airway 8-isoprostane from pre- to postexercise was greater in OW compared with OM and YC (p < 0.01), increasing ∼74% ± 77% in OW, while decreasing in OM (∼12% ± 50%) and YC (∼20.9% ± 30%). The OW exhibited a greater airway 8-isoprostane response to exhaustive exercise compared with OM and YC, which may suggest that sex differences in oxidative stress generation following exhaustive exercise may provide a mechanistic rationale for sex differences in late-onset respiratory diseases.
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Salminen, A., P. Saari, and M. Kihlström. "Age- and sex-related differences in lipid peroxidation of mouse cardiac and skeletal muscles." Comparative Biochemistry and Physiology Part B: Comparative Biochemistry 89, no. 4 (January 1988): 695–99. http://dx.doi.org/10.1016/0305-0491(88)90310-0.
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Pascoe, Christopher D., Sujata Basu, Jacquie Schwartz, Mario Fonseca, Shana Kahnamoui, Aruni Jha, Vernon Dolinsky, and Andrew J. Halayko. "Maternal diabetes promotes offspring lung dysfunction and inflammation in a sex-dependent manner." American Journal of Physiology-Lung Cellular and Molecular Physiology 322, no. 3 (March 1, 2022): L373—L384. http://dx.doi.org/10.1152/ajplung.00425.2021.
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Exposure to maternal diabetes is increasingly recognized as a risk factor for chronic respiratory disease in children. It is currently unclear; however, whether maternal diabetes affects the lung health of male and female offspring equally. This study characterizes the sex-specific impact of a murine model of diet-induced gestational diabetes (GDM) on offspring lung function and airway inflammation. Female adult mice are fed a high-fat (45% kcal) diet for 6 wk prior to mating. Control offspring are from mothers fed a low-fat (10% kcal) diet. Offspring were weaned and fed a chow diet until 10 wk of age, at which point lung function was measured and lung lavage was collected. Male, but not female, offspring exposed to GDM had increased lung compliance and reduced lung resistance at baseline. Female offspring exposed to GDM displayed increased methacholine reactivity and elevated levels of proinflammatory cytokines [e.g., interleukin (IL)-1β, IL-5, and CXCL1] in lung lavage. Female GDM offspring also displayed elevated abundance of matrix metalloproteinases (MMP) within their airways, namely, MMP-3 and MMP-8. These results indicate disparate effects of maternal diabetes on lung health and airway inflammation of male and female offspring exposed to GDM. Female mice may be at greater risk of inflammatory lung conditions, such as asthma, whereas male offspring display changes that more closely align with models of chronic obstructive pulmonary disease. In conclusion, there are important sex-based differences in the impact of maternal diabetes on offspring lung health that could signal differences in future disease risk.
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Stock, Matt S., Dustin J. Oranchuk, Adam M. Burton, and David C. Phan. "Age-, sex-, and region-specific differences in skeletal muscle size and quality." Applied Physiology, Nutrition, and Metabolism 45, no. 11 (November 2020): 1253–60. http://dx.doi.org/10.1139/apnm-2020-0114.
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Ultrasonography-derived cross-sectional area (CSA) and echo intensity (EI) are increasingly utilized by investigators to study muscle size and quality, respectively. We sought to examine age, sex, and region (proximal, middle, distal) differences in vastus lateralis and rectus femoris CSA and EI, and determine whether correction for subcutaneous fat thickness influences the magnitude of EI differences. Fifteen younger men (mean age = 23 years), 15 younger women (aged 21 years), 11 older men (aged 74 years), and 15 older women (aged 70 years) participated. Clear differences were observed among age, sex, and region for vastus lateralis CSA (p ≤ 0.013, d = 0.38–0.73), whereas rectus femoris CSA was only different between younger and older participants at the proximal region (p = 0.017, d = 0.65). Uncorrected EI was greatest at the distal region of both muscles (p < 0.001, d = 0.59–1.38), with only the younger men having significantly lower EI values than the other groups (p ≤ 0.043, d = 0.37–0.63). Subcutaneous fat correction resulted in a marked increase in the magnitude of sex-specific EI differences (p ≤ 0.032, d ≥ 0.42). Additionally, subcutaneous fat correction increased the uniformity of EI throughout the thigh. These findings highlight considerable region-specific differences in muscle size and quality among younger and older men and women and highlight the need to correct for subcutaneous fat thickness when examining EI. Novelty Rectus femoris CSA is similar between younger and older adults except at the most proximal site evaluated. Age- and sex-specific differences in uncorrected EI are nonuniform across the thigh. Correction for subcutaneous fat thickness substantially increased EI in women, resulting in greater sex differences.
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Lal, Charitharth Vivek, Jegen Kandasamy, Kalsang Dolma, Manimaran Ramani, Ranjit Kumar, Landon Wilson, Zubair Aghai, et al. "Early airway microbial metagenomic and metabolomic signatures are associated with development of severe bronchopulmonary dysplasia." American Journal of Physiology-Lung Cellular and Molecular Physiology 315, no. 5 (November 1, 2018): L810—L815. http://dx.doi.org/10.1152/ajplung.00085.2018.
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The pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. We previously identified differences in the airway microbiome at birth between preterm infants who were BPD predisposed versus those who were BPD resistant. In this study, we attempted to identify mechanisms by which the airway microbiome could modify the risk for BPD. We used a software-based method to predict the metagenome of the tracheal aspirate (TA) microbiome from 16S rRNA sequencing data in preterm infants and to identify functional ortholog genes that were differentially abundant in BPD-predisposed and BPD-resistant infants. We also identified metabolites that were differentially enriched in these samples by use of untargeted mass spectrometry and mummichog to identify the metabolic pathways involved. Microbial metagenome analysis identified specific pathways that were less abundant in the functional metagenome of the microbiota of BPD-predisposed infants compared with BPD-resistant infants. The airway metabolome of BPD-predisposed infants was enriched for metabolites involved in fatty acid activation and androgen and estrogen biosynthesis compared with BPD-resistant infants. These findings suggest that in extremely preterm infants the early airway microbiome may alter the metabolome, thereby modifying the risk of BPD. The differential enrichment of sex steroid metabolic pathways supports previous studies suggesting a role for sexual dimorphism in BPD risk. This study also suggests a role for metabolomic and metagenomic profiles to serve as early biomarkers of BPD risk.
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Yuri, Saori, Frida Madeni, Eri Shishido, and Shigeko Horiuchi. "Early adolescents’ knowledge of anatomy, sexual characteristics and contraception from reproductive health education in Bagamoyo, Tanzania: a cross-sectional study." African Journal of Midwifery and Women's Health 16, no. 4 (October 2, 2022): 1–11. http://dx.doi.org/10.12968/ajmw.2021.0033.
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Background/Aims Adolescent girls in Tanzania may drop out of school if they experience an unwanted pregnancy. Evidence shows that sex education can improve adolescents’ understanding of issues related to intercourse, pregnancy and contraception, but this education is lacking in Tanzania. In order to improve sex education in Tanziania, this study investigated early adolescents’ knowledge of anatomy, changes during puberty, pregnancy, contraception and safety. Methods This cross-sectional study was conducted among randomly selected 10−14-year-old students in a primary school in Bagamoyo, Tanzania. A questionnaire was used to gather data on participants’ knowledge of fundamental anatomy and physiology, sexual characteristics and contraception. Quantitative data were analysed using descriptive and inferential statistics, with P<0.05 used to determine significance. Results A total of 111 students (44 girls, 67 boys, from the fifth and sixth grades) participated. Significantly more boys than girls had begun talking to classmates about steady girl/boyfriends across both grades (P=0.003). The participants’ understanding of basic anatomy (including the functions of the heart, lungs and digestive system) was mostly high, although they scored low in some areas (pain, dentistry and facial muscles). When asked about pregnancy, contraception and safety, significantly more boys than girls could correctly identify appropriate contraception for teenagers (P=0.01). When analysed by grade, the boys’ grade had a significant impact on whether they correctly answered the questions on pregnancy (P=0.001) and contraception (P=0.001), but there were no differences in answers between girls of different grades. Conclusions Girls’ knowledge of pregnancy, contraception and safety was significantly lower than the boys, and despite beginning sex education in sixth grade, no significant differences in were observed between the fifth and sixth grade answers by the girls. The comprehensive sexual education programme for adolescent girls in Tanzania needs urgent improvement.
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Guenette, Jordan A., Andrea M. Martens, Anne L. Lee, Gradin D. Tyler, Jennifer C. Richards, Glen E. Foster, Darren E. R. Warburton, and A. William Sheel. "Variable effects of respiratory muscle training on cycle exercise performance in men and women." Applied Physiology, Nutrition, and Metabolism 31, no. 2 (April 1, 2006): 159–66. http://dx.doi.org/10.1139/h05-016.
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Respiratory muscle training (RMT) has been proposed as an effective means to increase the strength of the inspiratory muscles and improve exercise performance. The purpose of this study was to examine the effect of RMT on cycling time to exhaustion (TTE) and to determine any potential sex effect. We hypothesized that RMT would improve maximal inspiratory pressure (MIP) and TTE to a similar degreee in men and women. Males (n = 7; mean (± SD) age, 22.1 ± 1.5 y) and females (n = 8; mean (± SD) 24.5 ± 4.9 y) performed an incremental cycle test to determine maximal oxygen consumption ([Formula: see text]O2 max) (day 1), followed by a familiarization TTE (day 2) and baseline TTE (day 3) at 80% maximal work achieved during the [Formula: see text]O2 max test. Subjects then completed 5 weeks of respiratory muscle training (RMT) (5 d/week, 2 sets of 30 inspirations against 50% MIP). Four training sessions per week were performed at home and the 5th was supervised, during which the threshold load was increased if necessary. Following RMT, subjects completed 2 TTE tests (days 4 and 5). MIP increased in each subject (37% ± 18%, P < 0.05). There was no difference between men (pre = -100 ± 20 vs. post = -140 ± 29 cmH2O) and women (pre = -90 ± 28 vs. post = -117 ± 28 cmH2O). Baseline TTE (male = 301 ± 122 s; female = 338 ± 98 s) was shorter in comparison with the best of the 2 TTE-post tests (male = 353 ± 68 s; female = 416 ± 116 s; P < 0.01), but not when compared with days 4 or 5 (P > 0.05). RMT increases MIP and may improve exercise performance; however, improvements are variable with no differences between men and women.Key words: constant-intensity exercise, dyspnea, factors limiting exercise, maximal inspiratory pressure, respiratory muscles.
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Sanchez, Otto A., Elizabeth A. Copenhaver, Marti A. Chance, Michael J. Fowler, Theodore F. Towse, Jane A. Kent-Braun, and Bruce M. Damon. "Postmaximal contraction blood volume responses are blunted in obese and type 2 diabetic subjects in a muscle-specific manner." American Journal of Physiology-Heart and Circulatory Physiology 301, no. 2 (August 2011): H418—H427. http://dx.doi.org/10.1152/ajpheart.00060.2011.
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The purpose of this study was to determine whether there are differences in postisometric contraction blood volume and oxygenation responses among groups of type 2 diabetes mellitus (T2DM), obese, and lean individuals detectable using MRI. Eight T2DM patients were individually matched by age, sex, and race to non-T2DM individuals with similar body mass index (obese) and lean subjects. Functional MRI was performed using a dual-gradient-recalled echo, echo-planar imaging sequence with a repetition time of 1 s and at two echo times (TE = 6 and 46 ms). Data were acquired before, during, and after 10-s isometric dorsiflexion contractions performed at 50 and 100% of maximal voluntary contraction (MVC) force. MRI signal intensity (SI) changes from the tibialis anterior and extensor digitorum longus muscles were plotted as functions of time for each TE. From each time course, the difference between the minimum and the maximum postcontraction SI (ΔSI) were determined for TE = 6 ms (ΔSI6) and TE = 46 ms (ΔSI46), reflecting variations in blood volume and oxyhemoglobin saturation, respectively. Following 50% MVC contractions, the mean postcontraction ΔSI6 values were similar in the three groups. Following MVC only, and in the EDL muscle only, T2DM and obese participants had ∼56% lower ΔSI6 than the lean individuals. Also following MVC only, the ΔSI46 response in the EDL was lower in T2DM subjects than in lean individuals. These data suggest that skeletal muscle small vessel impairment occurs in T2DM and body mass index-matched subjects, in muscle-specific and contraction intensity-dependent manners.
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Shafiq, Mamoona, Erum Afaq, Tooba Zafar, Mehwish Qamar, Saima Qureshi, and Amna Faruqi. "Exogenous Progesterone Produces Significant Histomorphological Changes in the Lungs of Experimental BALB/c Mice." Pakistan Journal of Medical and Health Sciences 16, no. 8 (August 30, 2022): 338–41. http://dx.doi.org/10.53350/pjmhs22168338.
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Background: Progesterone is used in combined oral contraceptive pills and also has its effect on the respective receptors which are responsible for sexual development. Bronchial asthma emerges to be a major health issue in Pakistan with estimated prevalence is about 5% of the total population. Epidemiological studies highlight that one of the considerable risk factor for morbidity and mortality in inflammatory lung diseases is female gender. This suggests that sex-related hormones might play an imperative role in asthma disease progression. Understanding the biological role of sex hormones in regulating airway inflammation is crucial given the rising prevalence of chronic diseases among women worldwide. Aim: To determine the effect of progesterone on lungs of adult male mice by assessing and comparing the histological parameters e.g. bronchiolar smooth muscle size and peri-bronchial lymphocytic infiltration. Study Design: Randomized control trial Place and Duration of Study: Department of Physiology, Islamabad Medical & Dental College Islamabad in collaboration with National Institute of Health Islamabad from 1st October 2018 to 31st July 2019. Methodology: Sixty BALB/c mice were divided into 2 groups and each group comprised 30 mice. Group I (control group) received only distilled water and group 2 (norethisterone BP group) received pills mixed in distal water according to body weight of the mice respectively for 60 days. Results: In response to progesterone, 30% of the total mice had nil, 40% had mild, 26.7% of the total who showed moderate while severe PBLI was observed in 3.3% of the mice. Different frequencies of Bronchiolar Smooth Muscle Hyperplasia were observed when compared to Control group. Mild to moderate hyperplasia was produced by progesterone (norethisterone BP) group. Conclusion: Progesterone is the sexual hormone which modulates inflammatory processes in the lungs producing pulmonary inflammatory responses leading to asthma and also causes hyperplasia of the bronchiolar smooth muscles. Keywords: Progesterone, Asthma, Bronchiolar smooth muscle, Peri-bronchial lymphocytic Infiltration, BALB/c mice
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Tang, Rosalind, Abigail Fraser, and Maria Christine Magnus. "Female reproductive history in relation to chronic obstructive pulmonary disease and lung function in UK biobank: a prospective population-based cohort study." BMJ Open 9, no. 10 (October 2019): e030318. http://dx.doi.org/10.1136/bmjopen-2019-030318.
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ObjectivesSex differences in respiratory physiology and predilection for developing chronic obstructive pulmonary disease (COPD) have been documented, suggesting that female sex hormones may influence pathogenesis. We investigated whether aspects of female reproductive health might play a role in risk of COPD among women.DesignPopulation-based prospective cohort study.SettingUK Biobank recruited across 22 centres in the UK between 2006 to 2010.Primary and secondary outcomes measuresWe examined a range of female reproductive health indicators in relation to risk of COPD-related hospitalisation/death (n=271 271) using Cox proportional hazards regression; and lung function (n=273 441) using linear regression.ResultsParity >3 was associated with greater risk of COPD-related hospitalisation/death (adjusted HR 1.45; 95% CI: 1.16 to 1.82) and lower forced expiratory volume at 1 second/forced vital capacity ratio (FEV1/FVC) (adjusted mean difference −0.06; 95% CI: -0.07 to 0.04). Any oral contraception use was associated with lower risk of COPD-related hospitalisation/death (adjusted HR 0.85; 95% CI: 0.74 to 0.97) and greater FEV1/FVC (adjusted mean difference 0.01; 95% CI: 0.003 to 0.03). Late menarche (age >15) and early menopause (age <47) were also associated with greater risk of COPD-related hospitalisation/death (but not lung function), while endometriosis was associated with greater FEV1/FVC (not COPD-related hospitalisation/death). Early menarche (age <12 years) was associated with lower FEV1/FVC (but not COPD hospitalisation/death). Associations with polycystic ovary syndrome (PCOS) or ovarian cysts, any hormone replacement therapy (HRT) use, hysterectomy-alone and both hysterectomy and bilateral oophorectomy were in opposing directions for COPD-related hospitalisation/death (greater risk) and FEV1/FVC (positive association).ConclusionsMultiple female reproductive health indicators across the life course are associated with COPD-related hospitalisation/death and lung function. Further studies are necessary to understand the opposing associations of PCOS/ovarian cysts, HRT and hysterectomy with COPD and objective measures of airway obstruction.
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Petrov, M. E., K. Hasanaj, C. M. Hoffmann, D. R. Epstein, L. Krahn, J. G. Park, K. Hollingshead, et al. "0695 Sleepwell24, A Smartphone Application To Promote PAP Therapy Adherence: Feasibility And Acceptability." Sleep 43, Supplement_1 (April 2020): A265. http://dx.doi.org/10.1093/sleep/zsaa056.691.
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Abstract Introduction We aimed to test the feasibility and acceptability of SleepWell24, a multicomponent, smartphone-delivered intervention to increase positive airway pressure (PAP) adherence among newly diagnosed OSA patients. Methods SleepWell24 targets PAP adherence along with other health behaviors through education, trouble-shooting, goal-setting, and near real-time biofeedback of PAP machine use, and sleep and physical activity levels (via Fitbit integration), and other chronic disease self-management components. Patients with a first-time diagnosis of OSA (AHI≥5) and prescribed PAP therapy were enrolled from the Centers for Sleep Medicine at Mayo Clinic in Rochester, MN and Phoenix, AZ. Patients were randomized to SleepWell24 or usual care (UC) and assessed for PAP use over 60 consecutive nights. UC patients received a Fitbit monitor to control for non-specific intervention effects related to the introduction of a new personal technology. Feasibility was assessed with recruitment and retention rates and acceptability was assessed post-intervention with the validated, 8-item Treatment Evaluation Questionnaire (TEQ; range:0-4). ANCOVA models, adjusting for age, sex, and AHI severity, compared intervention arms on acceptability ratings. Results OSA patients were consented and randomized (N=111). Before the intervention began 4 participants withdrew, 12 were lost to follow-up, and 5 could not start the trial due to durable medical equipment (DME) vendor barriers. Ninety OSA patients (n=41 SleepWell24, n=49 UC; age M±SD=57.2±12.2; 44.4% female, 61.1% AHI≥15) started the intervention, with 2 participants withdrawing, 1 becoming deceased (unrelated to treatment) and 7 with missing PAP data due to DME vendor barriers. There was no significant between-groups differences on post-treatment acceptability (SleepWell24 M±SD=2.7±1.1 vs. UC M±SD=3.1±0.9, F[1,73]=2.3, p=0.11), and 77% of SleepWell24 participants found the app to be moderately to totally acceptable. Conclusion Overall, SleepWell24 was found to be feasible for delivery in two large clinical sleep medicine centers, and patients found the app to be acceptable. A number of challenges in trial delivery were encountered that have implications for scaled-up efficacy testing: (a) partnerships with DME vendors for near real-time PAP data integration; (b) alignment with clinical practice (i.e., referral, medical record integration); and (c) patient engagement. Support National Institute of Nursing Research / National Institutes of Health: R21NR016046
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LEWIS, P., and K. D. O’HALLORAN. "Sex Differences in Murine Sternohyoid Muscle Tolerance of Acute Severe Hypoxic Stress." Physiological Research, October 15, 2016, 843–51. http://dx.doi.org/10.33549/physiolres.933169.
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Given that sex differences inherent to muscle might at least contribute to male risk for obstructive sleep apnoea syndrome (OSAS), our objective was to test the hypothesis that male sternohyoid muscle exhibits greater susceptibility to severe hypoxic stress compared with female muscle. Adult male and female C57Bl6/J mouse sternohyoid isometric and isotonic functional properties were examined ex vivo at 35 °C in tissue baths under control and severe hypoxic conditions. Hypoxia was detrimental to peak force (Fmax), work (Wmax) and power (Pmax), but not shortening velocity (Vmax). Two-way analysis of variance revealed a significant sex x gas interaction for Fmax (p<0.05), revealing inferior hypoxic tolerance in male sternohyoid muscle. However, increases in male shortening velocity in severe hypoxia preserved power-generating capacity which was equivalent to values determined in female muscle. Fmax decline in hypoxic female sternohyoid was considerably less than in male muscle, illustrating an inherent tolerance of force-generating capacity mechanisms to hypoxic stress in female airway dilator muscle. We speculate that this could confer a distinct advantage in vivo in terms of the defense of upper airway caliber.
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Ekpruke, Carolyn Damilola, and Patricia Silveyra. "Sex Differences in Airway Remodeling and Inflammation: Clinical and Biological Factors." Frontiers in Allergy 3 (April 29, 2022). http://dx.doi.org/10.3389/falgy.2022.875295.
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Asthma is characterized by an increase in the contraction and inflammation of airway muscles, resulting in airflow obstruction. The prevalence of asthma is lower in females than in males until the start of puberty, and higher in adult women than men. This sex disparity and switch at the onset of puberty has been an object of debate among many researchers. Hence, in this review, we have summarized these observations to pinpoint areas needing more research work and to provide better sex-specific diagnosis and management of asthma. While some researchers have attributed it to the anatomical and physiological differences in the male and female respiratory systems, the influences of hormonal interplay after puberty have also been stressed. Other hormones such as leptin have been linked to the sex differences in asthma in both obese and non-obese patients. Recently, many scientists have also demonstrated the influence of the sex-specific genomic framework as a key player, and others have linked it to environmental, social lifestyle, and occupational exposures. The majority of studies concluded that adult men are less susceptible to developing asthma than women and that women display more severe forms of the disease. Therefore, the understanding of the roles played by sex- and gender-specific factors, and the biological mechanisms involved will help develop novel and more accurate diagnostic and therapeutic plans for sex-specific asthma management.
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Mann, Leah M., Sarah A. Angus, Connor J. Doherty, and Paolo B. Dominelli. "Evaluation of sex-based differences in airway size and the physiological implications." European Journal of Applied Physiology, July 31, 2021. http://dx.doi.org/10.1007/s00421-021-04778-2.
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Lesnick, Jason, Yefei Zhang, Justin X. Moore, Mohamud R. Daya, Jeffrey W. Jarvis, Graham Nichol, Jestin N. Carlson, et al. "Abstract 02: Effect of Airway Insertion First-Pass Success Upon Patient Outcomes in the Pragmatic Airway Resuscitation Trial." Circulation 140, Suppl_2 (November 19, 2019). http://dx.doi.org/10.1161/circ.140.suppl_2.02.
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Introduction: The multicenter Pragmatic Airway Resuscitation Trial (PART) demonstrated better adult out-of-hospital cardiac arrest (OHCA) outcomes with initial laryngeal tube (LT) insertion than endotracheal intubation (ETI) airway management. While emphasized in clinical practice, the effect of advanced airway insertion first-pass success (FPS) upon outcomes after OHCA is unknown. We sought to determine the direct and indirect mediating effects of LT and ETI FPS upon adult OHCA in a secondary analysis of PART. HYPOTHESES: 1) FPS associated with adult OHCA outcomes. 2) FPS mediates (explains) the association between airway type (LT vs. ETI) and adult OHCA outcomes. Methods: We defined FPS as successful LT insertion or ETI on the first attempt as reported by EMS personnel. We examined the outcomes return of spontaneous circulation (ROSC), 72-hour survival, hospital survival, and hospital survival with favorable neurologic function (MRS ≤3). Using multivariable GEE, we determined the association between FPS and outcomes after OHCA, adjusting for age, sex, witnessed arrest status, bystander CPR, initial rhythm, and trial randomization. Using the method of Baron and Kenny, we used mediation analysis to explain the contribution of FPS towards differences in OHCA outcomes between LT and ETI. Results: Of 3,004 patients enrolled in the trial, 1,423 received LT, 1,227 received ETI, 354 received bag-valve-mask ventilation only. FPS was: LT 90.3% and ETI 51.5%. FPS was associated with increased ROSC (adjusted OR 1.36, 95% CI 1.04-1.78) and 72h survival (1.45; 1.20-1.74) but not hospital survival (0.94; 0.67-1.31) or hospital survival with favorable neurologic function (0.70; 0.40-1.23). FPS had a strong mediating effect on the OHCA outcome differences between LT and ETI; 72h survival (74% mediated); ROSC (53% mediated); hospital survival (52% mediated); hospital survival with favorable neurologic status (35% mediated). Conclusion: In adult with OHCA, airway insertion FPS is associated with increased ROSC and 72h survival. Differences in OHCA outcomes between LT and ETI are largely explained by differences in FPS. EMS personnel should emphasize FPS in the advanced airway management of OHCA.
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Kurz, Michael C., David Prince, J. Christenson, J. Carlson, S. May, D. Stub, S. Cheskes, et al. "Abstract 277: Supraglottic Airway Use Is Associated with Higher Chest Compression Fraction than Endotracheal Intubation During Out-of-Hospital Cardiopulmonary Arrest." Circulation 130, suppl_2 (November 25, 2014). http://dx.doi.org/10.1161/circ.130.suppl_2.277.
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Objective: Chest compression interruptions - such as those from endotracheal intubation (ETI) - are associated with poorer out-of hospital cardiac arrest (OHCA) survival. Select Emergency Medical Services (EMS) practitioners substitute ETI with supraglottic airway (SGA) insertion to minimize these interruptions, but the resulting effects upon chest compression fraction (CCF) are unknown. We sought to determine the differences in CCF between adult OHCA receiving ETI and those receiving SGA. Methods: We studied adult, non-traumatic OHCA patients enrolled in the Resuscitation Outcomes Consortium (ROC) PRIMED trial. Chest compressions were measured using compression or thoracic impedance sensors. We limited the analysis to those receiving ETI or SGA and >2 minutes of chest compression data before and after airway insertion. We compared CCF between ETI and SGA before and after airway insertion, adjusting for age, sex, witnessed arrest, bystander CPR, shockable initial rhythm, public location, PRIMED trial arm, and regional ROC center. We also compared the change in CCF for each airway technique and stratified these analyses by initial rhythm. We analyzed the data using t-tests and multivariable linear regression. Results: Of 14,955 patients enrolled in the ROC PRIMED trial, we analyzed 2,767 cases, including 2051 ETI, 671 SGA, and 45 both. Unadjusted pre- and post- airway CCF was higher for SGA than ETI (pre- 0.732 vs 0.706, difference -0.026 95% CI -0.044, -0.008; post- 0.767 vs 0.724, difference -0.043 95% CI -0.060, -0.026). Adjusted post-airway CCF improved with both techniques, but the changes were not statistically significant (0.012 difference, 95% CI 0.036, -0.012, p-value 0.32). CCF differences were similar when stratified by initial rhythm. Conclusion: In this series SGA insertion was associated with a higher CCF than ETI and that difference persisted post-airway insertion. Advanced airway management strategy may minimally impact CCF.
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Novák, P., G. Zachařová, and T. Soukup. "Individual, age and sex differences in fiber type composition of slow and fast muscles of adult Lewis rats: comparison with other rat strains." Physiological Research, 2010, 783–801. http://dx.doi.org/10.33549/physiolres.931827.
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We analyzed fiber type composition of soleus and extensor digitorum longus (EDL) muscles of 3- to 19-month-old male and female inbred Lewis rats using histochemical demonstration of mATPase activity. The rats were divided into four groups of the mean age of 3, 6, 9 and 14 months. We found that the soleus muscle of 3-month-old rats contained significantly more of fast 2A fibers and less of slow type 1 fibers compared to older rats, while no significant difference was found between female and male rats at any age group. In contrast, we found no significant difference in the EDL fiber type composition among the age groups, but we found that the EDL muscle of female rats contained significantly less 2A fibers and more 2B fibers than that of male animals. Our results thus revealed an age difference in the soleus muscle and a sex difference in the EDL muscle among postnatal Lewis rats. The number of slow type 1 fibers in the soleus muscle varied between 87 and 100 % and that of 2A fibers between 13 and 0 %. In the EDL the percentage of type 1 fibers varied between 2.6 and 8.7 %, that of 2A fibers between 12.6 and 25.8 % and that of 2B fibers between 70.4 and 81.6 %. Both muscles thus exhibited a considerable degree of variability among individual animals even in the same age group. Furthermore, a comparison of the Lewis rats with literature data of other rat strains showed that the number of fast 2A fibers in the soleus muscle of 4-month-old and older animals decreased in this order: SHR > Lister Hooded > Fisher 344 > SpragueDawley > Wistar > WBN/Kob > Lewis strain, being almost 20 % in the SHR and less than 2 % in the Lewis rats. In contrast, the “fastest” composition (judged according to the percentage of the fastest 2B fibers) of the EDL muscle was demonstrated by Lewis, Wistar and Fisher 344 rats (about 75 %), while Sprague-Dawley and WBN/Kob rats contained only about 50 % of 2B fibers. The percentage of slow type 1 fibers in the EDL was low in all strains (about 5 %). Our results thus show that the individual, age and sex as well as inter-strain differences in muscle fiber type composition should not be ignored when comparing results of different studies. We also demonstrated that the inbred Lewis strain appears to have more “specialized” muscle composition, as its soleus is the “slowest” and its EDL is the “fastest” among the routinely used rat strains.
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Lupton, Joshua, Robert Schmicker, Mohamud Daya, Tom Aufderheide, Shannon Stephens, Nancy Le, Graham Nichol, Henry Wang, and Matthew Hansen. "Abstract 165: Association of Advanced Airway Placement and Time to Epinephrine Administration in Patients With Out-of-Hospital Cardiac Arrest." Circulation 138, Suppl_2 (November 6, 2018). http://dx.doi.org/10.1161/circ.138.suppl_2.165.
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Introduction: Out-of-hospital cardiac arrest (OHCA) remains a significant source of morbidity and mortality in the United States. In addition to cardiopulmonary resuscitation (CPR) and defibrillation, epinephrine and advanced airway management are often used in treatment. Recent studies suggest early administration of epinephrine is associated with improved survival. The purpose of this study was to evaluate the effect of airway type on timing to epinephrine in OHCA. Hypothesis: Patients who had laryngeal tube (LT) insertion as first attempted airway have shorter times to epinephrine administration compared to those with endotracheal intubation (ETI) as first attempted airway. Methods: Subjects enrolled in the Pragmatic Airway Resuscitation Trial who received epinephrine and primary ETI or LT were included. The dependent variable was timing to epinephrine administration after EMS arrival in minutes, the independent variable was first airway attempted (LT or ETI). Kaplan-Meier estimates of time to drug administration were used to account for censoring. Results: We included 2650 subjects (1423 LT and 1227 ETI). There were no significant differences in age, sex, first rhythm, EMS response time, witnessed arrest status, bystander CPR or proportion receiving epinephrine between the LT and ETI groups. Among all OHCA patients, LT and ETI had median minutes (95% CI) until epinephrine administration of 9.3 (9.0, 9.8) and 9.7 (9.4, 10.0), respectively (p=n.s.). For the VT/VF subgroup, the median minutes (95% CI) to epinephrine administration were 8.0 (7.8, 9.0) and 9.2 (8.7, 9.9) for LT and ETI, respectively (Figure, p=n.s.). Conclusions: Overall, advanced airway type did not affect time to epinephrine. Among those with initial VT/VF, there is a weak, non-statistically significant trend of longer time to epinephrine when ETI is used compared to LT. This difference may be a contributing component to improved survival with an initial LT airway strategy for OHCA.
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Chang, Hansol, Jin Ho Choi, and DAUN JEONG. "Abstract 11045: Pre-Hospital Airway for Out-of-Hospital Cardiac Arrest: A Nationwide Multicenter Study." Circulation 144, Suppl_2 (November 16, 2021). http://dx.doi.org/10.1161/circ.144.suppl_2.11045.
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Introduction: This study investigated whether use of pre-hospital advanced airway management (AAM) is associated with improved survival of adults with out-of hospital cardiac arrest (OHCA) compared to conventional bag-valve-mask ventilation (BVM). Method: The study subjects were derived from Korean Cardiac Arrest Research Consortium (KoCARC), a multi-center OHCA registry of Korea. Patients who underwent AAM or BVM using supraglottic airway, oropharyngeal airway, or endotracheal intubation were compared. The differences in baseline clinical characteristics were adjusted using propensity scoring matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was 30-day survival with neurologically favorable status of cerebral performance category ≤2. The outcome was also compared according to the duration of low-flow time. Results: Of 9,616 patients enrolled, (median age = 71, male sex = 65%) there were 7,583 AAM and 2,033 BVM patients. The unadjusted survival to with neurologically favorable status was lower in AAM compared to BVM (HR = 1.27, 95% confidence interval (CI) = 1.20 - 1.34, p<0.001). However, there was no significant difference of survival to with neurologically favorable status between AAM and BVM after PSM or ITPW-adjusted comparisons (p>0.05, all). This finding was consistent irrespective of duration of low-flow time. Conclusion: In this nationwide real-world data of out-of hospital cardiac arrest study, prehospital advanced airway management compared to bag-and-mask ventilation did not result in an improved clinical outcome at 30 days.
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Bonette, Austin, Tom P. Aufderheide, Graham Nichol, Jeffrey Jarvis, Matthew L. Hansen, Riccardo Colella, Jason Lesnick, Jestin N. Carlson, Shannon W. Stephens, and Henry E. Wang. "Abstract 201: Bougie-Assisted Endotracheal Intubation in the Pragmatic Airway Resuscitation Trial." Circulation 142, Suppl_4 (November 17, 2020). http://dx.doi.org/10.1161/circ.142.suppl_4.201.
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Objective: Paramedics often perform endotracheal intubation (ETI) in the management of out-of-hospital cardiac arrest (OHCA). While ETI assisted by use of the gum elastic Bougie has been associated with improved first-pass intubation success in the emergency department, its influence upon out-of-hospital cardiac arrest (OHCA) ETI is unknown. We compared success rates and outcomes between Bougie-assisted and standard ETI in the Pragmatic Airway Resuscitation Trial (PART). Methods: We conducted a secondary analysis of PART, a clinical trial comparing initial-ETI vs. initial-laryngeal tube airway management strategies in adult OHCA. We included only patients receiving initial ETI attempts. The primary exposure was Bougie-assisted vs. standard ETI. The primary outcome was first-pass ETI success. Secondary outcomes included overall ETI success, time to successful ETI, 72-hour survival, hospital survival and hospital survival with favorable neurologic status. We assessed the associations between Bougie-assistance and ETI outcomes using Generalized Estimating Equations and Cox Regression, adjusting for for age, sex, race, witnessed arrest, bystander CPR and initial rhythm. Results: Of the 3,004 patients enrolled in PART, 1,227 received initial ETI, including 440 Bougie-assisted and 787 standard ETI. First-pass ETI success did not differ between Bougie-assisted and standard ETI (53.1% vs. 42.8%; adjusted OR 1.12, 95% CI: 0.97 to 1.39). Overall ETI success was slightly higher for Bougie-assisted ETI (56.2% vs. 49.1%; adjusted OR 1.19, 95% CI: 1.01 to 1.32). Time to ETI was longer for Bougie-assisted than standard ETI (median 13 vs. 11 min; adjusted HR 0.63, 95% CI: 0.45 to 0.90). While survival to hospital discharge was lower for Bougie-assisted than standard ETI (3.6% vs. 7.5%; adjusted OR 0.94, 95% CI: 0.92 to 0.96), there were no differences in 72-hour survival or hospital survival with favorable neurologic status. Conclusion: In the PART trial, Bougie assistance resulted in slightly higher overall ETI success but with longer airway placement time. Bougie assistance was not associated with first-pass ETI success. The association between Bougie-assisted ETI and OHCA survival was unclear. The role of Bougie-assisted ETI in OHCA is uncertain.
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Konrad, Andreas, Masatoshi Nakamura, Florian K. Paternoster, Markus Tilp, and David G. Behm. "A comparison of a single bout of stretching or foam rolling on range of motion in healthy adults." European Journal of Applied Physiology, March 17, 2022. http://dx.doi.org/10.1007/s00421-022-04927-1.
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Abstract Purpose Stretching and foam rolling are common warm-up exercises and can acutely increase the range of motion (ROM) of a joint. However, possible differences in the magnitude of change on ROM between these two interventions on the immediate and prolonged effects (e.g., 10 min after the intervention) are not yet well understood. Thus, the purpose of this review was to compare the immediate and prolonged effects of a single bout of foam rolling with a single bout of stretching on ROM in healthy participants. Methods In total, 20 studies with overall 38 effect sizes were found to be eligible for a meta-analysis. For the main analysis, subgroup analysis, we applied a random-effect meta-analysis, mixed-effect model, respectively. The subgroup analyses included age groups, sex, and activity levels of the participants, as well as the tested muscles, the duration of the application, and the study design. Results Meta-analyses revealed no significant differences between a single stretching and foam rolling exercise immediately after the interventions (ES = 0.079; P = 0.39) nor a difference 10 min (ES = − 0.051; P = 0.65), 15 min (ES = − 0.011; P = 0.93), and 20 min (ES = − 0.161; P = 0.275) post-intervention. Moreover, subgroup analyses revealed no other significant differences between the acute effects of stretching and foam rolling (P > 0.05). Conclusion If the goal is to increase the ROM acutely, both interventions can be considered as equally effective. Likely, similar mechanisms are responsible for the acute and prolonged ROM increases such as increased stretch tolerance or increased soft-tissue compliance.
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Watanabe, Hideki, Kunio Nakagawa, and Masaaki Kakihana. "Abstract 1428: Effects of Continuous Positive Airway Pressure Treatment on Endothelial Function and Insulin Resistance in Patients with Obstructive Sleep Apnea and the Metabolic Syndrome." Circulation 116, suppl_16 (October 16, 2007). http://dx.doi.org/10.1161/circ.116.suppl_16.ii_294.
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Background: Obstructive sleep apnea (OSA) and the metabolic syndrome are recognized as a risk factor for cardiovascular disease. Cardiovascular events have been reported to have a peak incidence in the early hours after waking in OSA patients. This study was designed to examine the influence of OSA on endothelial function in the early morning in patients with the metabolic syndrome. Methods: The severity of sleep-disordered breathing was evaluated by polysomnography in patients with the metabolic syndrome. Ten OSA patients (an apnea-hypopnea index [AHI] >30) with the metabolic syndrome was included in this study, and we also included age-and sex-matched ten non-OSA patients (AHI <5) with the metabolic syndrome in this study. All subjects received pioglitazone for 1 month (1Mo), and then OSA patients received pioglitazone and nasal continuous positive airway pressure (CPAP) treatment for next 1 month (2Mo). Flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of brachial artery were measured by using ultrasound system. We also assessed insulin resistance by HOMA-IR. Measurements were performed in the early morning (6:00AM) and the late morning (11:00AM) at baseline, 1Mo, and 2Mo. Results: At baseline, there were not differences in FMD, and NID between the early morning and the late morning. After the treatment with pioglitazone (1Mo), FMD in the non-OSA patients was increased in the early and late morning, but FMD in the OSA patients was increased only in the late morning. After the CPAP treatment (2Mo), FMD in the OSA patients was increased in the early and late morning. HOMA-IR was improved at 1Mo in the non-OSA patients, and was improved at 2Mo in the OSA patients. Conclusion: OSA is associated with endothelial dysfunction in the early morning and insulin resistance in patients with the metabolic syndrome, and CPAP treatment is effective on the improvement of endothelial dysfunction in the early morning in OSA patients with the metabolic syndrome.
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Okubo, Masashi, Cameron Dezfulian, Francis X. Guyette, Christian Martin-Gill, Sylvia Owusu-Ansah, and Clifton W. Callaway. "Abstract 126: Intravenous Versus Intraosseous Epinephrine Administration for Pediatric Patients with Out-of-hospital Cardiac Arrest." Circulation 142, Suppl_4 (November 17, 2020). http://dx.doi.org/10.1161/circ.142.suppl_4.126.
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Introduction: The 2015 American Heart Association Guidelines for Cardiopulmonary Resuscitation recommend intravenous (IV) or intraosseous (IO) epinephrine administration for pediatric patients with out-of-hospital cardiac arrest (OHCA). However, it is unknown whether the route of epinephrine administration affects patient outcomes. Our objective was to evaluate the association between the route of epinephrine administration and survival. Methods: We conducted a secondary analysis of the Resuscitation Outcomes Consortium Epistry, a prospective multicenter OHCA registry from 2011 through 2015 in North America. We included pediatric patients (≤18 years) with OHCA for whom emergency medical services (EMS) providers attempted resuscitation and administered epinephrine via IV or IO. We excluded patients who received endotracheal epinephrine, received both IV and IO epinephrine, received IV epinephrine with failed IO access, and received IO epinephrine with failed IV access. The primary outcome was survival to hospital discharge. We used multivariable logistic regression and adjusted for age, sex, initial rhythm, location of arrest, witness status, receiving layperson cardiopulmonary resuscitation, 9-1-1 call to EMS arrival, and advanced airway management. We also conducted a propensity score matching analysis with the same covariates. Results: Of the eligible 831 pediatric patients with OHCA, 226 (27.2%) received IV epinephrine and 605 (72.8%) IO epinephrine. Median interval between 9-1-1 call and epinephrine administration was 16.4 minutes (interquartile range [IQR] 12.9-21.0) in IV group and 16.2 minutes (IQR 12.8-20.0) in IO group. In the logistic regression model, the adjusted odds ratio (OR) of the IO group for survival to hospital discharge was 0.99 (95% confidence interval [CI] 0.41-2.40), compared with the IV group. Similarly, in the propensity score analysis, 218 patients underwent matching with good balance (standardized differences <0.25 for all covariates) and the OR of the IO group for survival to hospital discharge was 1.00 (95% CI 0.38-2.62). Conclusions: We observed no significant difference in survival to hospital between pediatric patients with OHCA who received epinephrine via IV and IO routes.