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Infectious mastitis is a common condition that affects up to 33% of lactating women. Several risk factors have been suggested to be strongly associated with breast abscess, nipple infection, and non-purulent mastitis associated with childbirth. In this retrospective cohort study, we gathered data from the National Inpatient Sample (NIS) between 2005 and 2014 and utilized data stratification and backward linear regression to analyze the predictive factors associated with patients hospitalized with breast infection after childbirth, with special consideration of risk factors affecting hospital length of stay (LOS). In the ten-year period, 4614 women were hospitalized with a primary diagnosis of breast abscess, nipple infection, or non-purulent mastitis associated with childbirth. Mean (SD) age was 26.75 (6) years. The highest frequency distribution of cases was observed in patients aged 22–30 years (49.82%). Mean (SD) LOS was 2.83 (1.95) days. Mean (SD) LOS in patients with procedure was 3.53 (2.47) days, which was significantly longer than that in those with no procedure (2.39 (1.36) days, p < 0.001). Primary diagnosis of breast abscess and occurrence of a hospital procedure were most significantly associated with prolonged LOS. Factors such as age, socioeconomic position, severity of functional loss, as well as comorbidities were also contributing risk factors to the development of breast infection and increased hospital LOS. Further studies should examine these findings, as they relate to breastfeeding practices and concentrate on establishing best practices for risk reduction and prevention of childbirth-associated breast and nipple infections and hospitalizations.

International audience; The still unexplained daytime HONO concentration in the Earth’s atmosphere and the impact of water on the HONO chemistry have been a mystery for decades. Several pathways and many modeling methods have failed to reproduce the atmospheric measurements. We reveal in this study the first spectroscopic observation and characterization of the complex of HONO with water observed through its rotational signature. Under the experimental conditions, HONO–water is stable, particularly straightforward to form, and features intense absorption signals. This could explain both the influence of water on the HONO chemistry and the missing HONO sources, as well as the missing contribution of many other molecules of atmospheric relevance that skew the accuracy of field measurements and the full account of partitioning species in the atmosphere.

Epinephrine (EPI), an endogenous catecholamine involved in the body’s fight-or-flight responses to stress, activates α1-adrenergic receptors (α1ARs) expressed on various organs to evoke a wide range of physiological functions, including vasoconstriction. In the smooth muscle of human bronchi, however, the functional role of EPI on α1ARs remains controversial. Classically, evidence suggests that EPI promotes bronchodilation by stimulating β2-adrenergic receptors (β2ARs). Conventionally, the selective β2AR agonism of EPI was thought to be, in part, due to a predominance of β2ARs and/or a sparse, or lack of α1AR activity in human airway smooth muscle (HASM) cells. Surprisingly, we find that HASM cells express a high abundance of ADRA1B (the α1AR subtype B) and identify a spontaneous “switch-like” activation of α1ARs that evokes intracellular calcium, myosin light chain phosphorylation, and HASM cell shortening. The switch-like responses, and related EPI-induced biochemical and mechanical signals, emerged upon pharmacological inhibition of β2ARs and/or under experimental conditions that induce β2AR tachyphylaxis. EPI-induced procontractile effects were abrogated by an α1AR antagonist, doxazosin mesylate (DM). These data collectively uncover a previously unrecognized feed-forward mechanism driving bronchospasm via two distinct classes of G protein-coupled receptors (GPCRs) and provide a basis for reexamining α1AR inhibition for the management of stress/exercise-induced asthma and/or β2-agonist insensitivity in patients with difficult-to-control, disease subtypes.

The microwave spectrum of 2-methylthiophene was recorded in a frequency range from 2 to 26.5 GHz using a molecular-jet Fourier transform microwave spectrometer with a Fabry–Pérot type resonator chamber and coaxial arrangement of the resonator and the molecular beam. Measuring and assigning spectra of the 34S and 13C isotopologues allowed the determination of the semiexperimental equilibrium structure (reSE). Comparing the structure to that of thiophene revealed a decrease in the ∠(S−C2−C3) angle from 111.595(6)° to 111.37(1)° by addition of the methyl group to the C(2) position, as well as an increase in the S−C2 bond length from 1.7102(1) Å to 1.7219(2) Å. A–E splittings from internal rotation of the methyl group were observed, and the V3 potential in the vibrational ground state was determined to be 197.7324(18) cm−1. The V3 value and the rotational constants A, B, C were calculated with a large number of different methods and basis sets for benchmarking purposes by comparing them to the fitted parameters. The V3 value was also compared to those of other thiophene and furan derivatives to gain a better understanding of the steric and electrostatic effects in these classes of compounds.

This article presents an analysis of spurious signals’ influence on automatic frequency control (AFC) in EPR spectrometers. The primary source of spurious signals is leakage across the circulator in the microwave bridge. Additionally, the signals reflected from connectors in the line between the circulator and the resonator modify that signal. Spurious signals may degrade the performance of AFC, significantly offsetting lock points from the center frequency of the resonator. The offset’s size depends on the parameters of the resonator and the amount of the circulator isolation. It can be minimized by the appropriate use of a phase shifter located in the line between the circulator and the resonator. Another way to avoid these problems is to introduce a leakage compensation arm to the microwave bridge.

N-methyl-d-aspartate (NMDA) receptors are widely expressed in the central nervous system. However, their presence and function at extraneuronal sites is less well characterized. In the present study, we examined the expression of NMDA receptor subunit mRNA and protein in human pulmonary artery (HPA) by quantitative polymerase chain reaction (PCR), immunohistochemistry and immunoblotting. We demonstrate that both GluN1 and GluN2 subunit mRNAs are expressed in HPA. In addition, GluN1 and GluN2 (A–D) subunit proteins are expressed by human pulmonary artery smooth muscle cells (HPASMCs) in vitro and in vivo. These subunits localize on the surface of HPASMCs and form functional ion channels as evidenced by whole-cell patch-clamp electrophysiology and reduced phenylephrine-induced contractile responsiveness of human pulmonary artery by the NMDA receptor antagonist MK801 under hypoxic condition. HPASMCs also express high levels of serine racemase and vesicular glutamate transporter 1, suggesting a potential source of endogenous agonists for NMDA receptor activation. Our findings show HPASMCs express functional NMDA receptors in line with their effect on pulmonary vasoconstriction, and thereby suggest a novel therapeutic target for pharmacological modulations in settings associated with pulmonary vascular dysfunction.

Miller, RM, Freitas, EDS, Heishman, AD, Koziol, KJ, Galletti, BAR, Kaur, J, and Bemben, MG. Test-retest reliability between free weight and machine-based movement velocities. J Strength Cond Res 34(2): 440-444, 2020-Several devices are available to measure muscular power through velocity measurement, including the Tendo FitroDyne. The ability for such devices to produce consistent results is still questioned, and the reproducibility of measurement between free weight and machine exercise has yet to be examined. Therefore, the aim of this investigation was to determine the test-retest reliability for barbell velocity during the bench press (BP) and weight velocity during the 2 leg press (2LP) for loads corresponding to 20-80% of 1 repetition maximum (1RM). Forty recreationally active individuals (22.6 ± 2.5 years; 175.9 ± 10.8 cm; and 76.2 ± 13.2 kg) with a 1RM BP and 2LP of 66.8 ± 32.4 kg and 189.5 ± 49 kg, respectively, volunteered for this study. Subjects completed 1 familiarization visit preceding 3 testing visits, which encompassed 1RM determination and 2 days of velocity testing. Forty-eight hours after 1RM testing, the subjects performed 1 repetition at 20, 30, 40, 50, 60, 70, and 80% of their 1RM for each exercise in randomized order. Subjects returned to the laboratory 1 week later to perform the velocity assessment again in randomized order. Intraclass correlation coefficient (ICC2,1) and relative SEM for the BP and 2LP ranged from 0.56 to 0.98 (3-18.1%) and 0.78 to 0.98 (2.8-7.2%), respectively, and no mean differences were observed between trials. The results suggest high reliability for BP velocity between 30 and 60% 1RM and moderate reliability at 20, 70, and 80% 1RM, while the 2LP displayed high to excellent reliability from 20 to 80% 1RM. Cumulatively, machine-based exercise displayed greater reproducibility; however, additional machine exercises need to be examined to bolster this conclusion.

The soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate signaling pathway evokes vascular smooth muscle relaxation; whether this pathway mediates airway smooth muscle relaxation remains controversial. We posit that sGC activators are equi-effective as β-agonists in reversing contractile agonist-induced airway smooth muscle shortening. To provide clarity, we tested the efficacy of sGC stimulator and activator drugs, BAY 41-2272 and BAY 60-2270, respectively, in reversing bronchoconstriction of human small airways using human precision-cut lung slices (hPCLS). Both BAY drugs reversed carbachol-induced bronchoconstriction to a maximal degree comparable to that of formoterol. Moreover, the sGC drugs remained effective bronchodilators despite formoterol-induced desensitization of the airways. Analysis of the hPCLS after their activation by sGC or β2-adrenergic receptor agonist showed distinct cyclic nucleotide accumulation in the hPCLS. Collectively, these data suggest that cAMP and cyclic guanosine monophosphate pathways are equi-effective for reversing carbachol-induced bronchoconstriction in the human airway via separate and distinct second messenger pathways. This should open the door for future studies to test whether sGC-targeted drugs alone or in combination can serve as effective bronchodilators in asthma and chronic obstructive pulmonary disease.

In most living cells, the second-messenger roles for adenosine 3′,5′-cyclic monophosphate (cAMP) are short-lived, confined to the intracellular space, and tightly controlled by the binary switch–like actions of Gα(s) (stimulatory G protein)–activated adenylyl cyclase (cAMP production) and cAMP-specific PDE (cAMP breakdown). Here, by using human airway smooth muscle (HASM) cells in culture as a model, we report that activation of the cell-surface β(2)AR (β(2)-adrenoceptor), a G(s)-coupled GPCR (G protein–coupled receptor), evokes cAMP egress to the extracellular space. Increased extracellular cAMP levels ([cAMP](e)) are long-lived in culture and are induced by receptor-dependent and receptor-independent mechanisms in such a way as to define a universal response class of increased intracellular cAMP levels ([cAMP](i)). We find that HASM cells express multiple ATP-binding cassette (ABC) membrane transporters, with ABCC1 (ABC subfamily member C 1) being the most highly enriched transcript mapped to MRPs (multidrug resistance–associated proteins). We show that pharmacological inhibition or downregulation of ABCC1 with siRNA markedly reduces β(2)AR-evoked cAMP release from HASM cells. Furthermore, inhibition of ABCC1 activity or expression decreases basal tone and increases β-agonist–induced HASM cellular relaxation. These findings identify a previously unrecognized role for ABCC1 in the homeostatic regulation of [cAMP](i) in HASM that may be conserved traits of the G(s)-GPCRs (G(s)-coupled family of GPCRs). Hence, the general features of this activation mechanism may uncover new disease-modifying targets in the treatment of airflow obstruction in asthma. Surprisingly, we find that serum cAMP levels are elevated in a small cohort of patients with asthma as compared with control subjects, which warrants further investigation.

Vertebrate embryogenesis involves a conserved and fundamental process, called the maternal-to-zygotic transition (MZT), which marks the switch from a maternal factors-dominated state to a zygotic factors-driven state. Yet the precise mechanism underlying MZT remains largely unknown. Here we report that the RNA helicase Ddx3xb in zebrafish undergoes liquid-liquid phase separation (LLPS) via its N-terminal intrinsically disordered region (IDR), and an increase in ATP content promotes the condensation of Ddx3xb during MZT. Mutant form of Ddx3xb losing LLPS ability fails to rescue the developmental defect of Ddx3xb-deficient embryos. Interestingly, the IDR of either FUS or hnRNPA1 can functionally replace the N-terminal IDR in Ddx3xb. Phase separation of Ddx3xb facilitates the unwinding of 5' UTR structures of maternal mRNAs to enhance their translation. Our study reveals an unprecedent mechanism whereby the Ddx3xb phase separation regulates MZT by promoting maternal mRNA translation.

Glucocorticoids are widely used for the suppression of inflammation, but evidence is growing that they can have rapid, non-genomic actions that have been unappreciated. Diverse cell signaling effects have been reported for glucocorticoids, leading us to hypothesize that glucocorticoids alone can swiftly increase the 3',5'-cyclic adenosine monophosphate (cAMP) production. We found that prednisone, fluticasone, budesonide, and progesterone each increased cAMP levels within 3 minutes without phosphodiesterase inhibitors by measuring real-time cAMP dynamics using the cAMP difference detector in situ assay in a variety of immortalized cell lines and primary human airway smooth muscle (HASM) cells. A membrane- impermeable glucocorticoid showed similarly rapid stimulation of cAMP, implying that responses are initiated at the cell surface. siRNA knockdown of Gαs virtually eliminated glucocorticoid-stimulated cAMP responses, suggesting that these drugs activate the cAMP production via a G protein-coupled receptor. Estradiol had small effects on cAMP levels but G protein estrogen receptor antagonists had little effect on responses to any of the glucocorticoids tested. The genomic and non-genomic actions of budesonide were analyzed by RNA-Seq analysis of 24 hours treated HASM, with and without knockdown of Gαs . A 140-gene budesonide signature was identified, of which 48 genes represent a non-genomic signature that requires Gαs signaling. Collectively, this non-genomic cAMP signaling modality contributes to one-third of the gene expression changes induced by glucocorticoid treatment and shifts the view of how this important class of drugs exerts its effects.

Airway smooth muscle is the primary cell mediating bronchomotor tone. The milieu created in the asthmatic lung modulates airway smooth muscle contractility and relaxation. Experimental findings suggest intrinsic abnormalities in airway smooth muscle derived from patients with asthma in comparison with airway smooth muscle from those without asthma. These changes to excitation-contraction pathways may underlie airway hyperresponsiveness and increased airway resistance associated with asthma.

Airway smooth muscle plays a pivotal role in modulating bronchomotor tone. Modulation of contractile and relaxation signaling is critical to alleviate the airway hyperresponsiveness (AHR) associated with asthma. Emerging studies examining the phenotype of ASM in the context of asthma provide rich avenues to develop more effective therapeutics to attenuate the AHR associated with the disease.

This article describes a novel digital L-band EPR spectrometer. The spectrometer uses direct digital detection with time-locked subsampling (TLSS). The device consists of a microwave bridge equipped with a microwave source based on direct digital synthesis (DDS) and a digital receiver. DDS technology combined with an ultra-low noise 1 GHz master clock allowed the development of a digitally controlled microwave source with exceptionally good phase noise characteristics. The obtained level of phase noise is as low as −140 dBc/Hz at 30.5 kHz from the carrier frequency of 1.15 GHz, which is important when registering the EPR dispersion signal. The receiver is equipped with a high-speed A/D converter that enables direct digitalization of the L-band microwave signal. The obtained discrete data are then buffered and averaged in a programmable logic FPGA device. Data packets from FPGA are transferred to a DSP microcontroller that correlates them with the appropriate reference signals. This detection algorithm requires time locking of the generator and the receiver, which is ensured by clocking both devices from the same reference source. This procedure allows the simultaneous detection of the absorption and dispersion signals at the magnetic field modulation frequency and at any of its harmonics. The software to control the spectrometer was designed in the LabView programming environment. The program also allows further data processing. To the best of our knowledge, the described spectrometer is one of the first full implementation of the direct digital detection technique which could replace conventional analog CW spectrometers that utilize magnetic field modulation. For an 11 µm aqueous TEMPOL solution, the new spectrometer obtained a S/N ratio greater than 160 for an EPR spectrum registered in 69 s.

Obesity is emerging as a global public health epidemic. The co-morbidities associated with obesity significantly contribute to reduced quality of life, mortality, and global healthcare burden. Compared to other asthma comorbidities, obesity prominently engenders susceptibility to inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), contributes to greater disease severity and evokes insensitivity to current therapies. Unlike in other metabolic diseases associated with obesity, the mechanistic link between obesity and airway diseases is only poorly defined. Transforming growth factor-β (TGF-β) is a pleiotropic inflammatory cytokine belonging to a family of growth factors with pivotal roles in asthma. In this review, we summarize the role of TGF-β in major obesity-associated co-morbidities to shed light on mechanisms of the diseases. Literature evidence shows that TGF-β mechanistically links many co-morbidities with obesity through its profibrotic, remodeling, and proinflammatory functions. We posit that TGF-β plays a similar mechanistic role in obesity-associated inflammatory airway diseases such as asthma and COPD. Concerning the role of TGF-β on metabolic effects of obesity, we posit that TGF-β has a similar mechanistic role in obesity-associated inflammatory airway diseases in interplay with different comorbidities such as hypertension, metabolic diseases like type 2 diabetes, and cardiomyopathies. Future studies in TGF-β-dependent mechanisms in obesity-associated inflammatory airway diseases will advance our understanding of obesity-induced asthma and help find novel therapeutic targets for prevention and treatment., Graphical abstract Obesity amplifies airway hyperreactivity in asthma, potentially through TGF-β1-mediated proinflammatory, profibrotic and mitogenic mechanisms.Image 1, Highlights • Obesity is a serious global health issue, and is associated with inflammatory airways diseases. • TGF-β1 is a cytokine present in a number of inflammatory disorders. • Mechanisms underlying obesity-induced airways diseases are unclear. • The role of TGF-β1 in obesity-induced airway diseases remains largely unknown.

The spectra of N-ethyl methyl amine, CH

A subset of asthmatics develop a severe form of the disease whose etiology involves airway inflammation along with inherent drivers that remain ill-defined. To address this, we studied human airway smooth muscle cells (HASMC), whose relaxation drives airway bronchodilation and whose dysfunction contributes to airway obstruction and hypersensitivity in severe asthma. Because HASMC relaxation can be driven by the NO-soluble guanylyl cyclase (sGC)-cGMP signaling pathway, we questioned if HASMC from severe asthma donors might possess inherent defects in their sGC or in redox enzymes that support sGC function. We analyzed HASMC primary lines derived from 17 severe asthma and 16 normal donors and corresponding lung tissue samples regarding sGC activation by NO or by pharmacologic agonists, and also determined expression levels of sGC α1 and β1 subunits, supporting redox enzymes, and related proteins. We found a majority of the severe asthma donor HASMC (12/17) and lung samples primarily expressed a dysfunctional sGC that was NO-unresponsive and had low heterodimer content and high Hsp90 association. This sGC phenotype correlated with lower expression levels of the supporting redox enzymes cytochrome b5 reductase, catalase, and thioredoxin-1, and higher expression of heme oxygenases 1 and 2. Together, our work reveals that severe asthmatics are predisposed toward defective NO-sGC-cGMP signaling in their airway smooth muscle due to an inherent sGC dysfunction, which in turn is associated with inherent changes in the cell redox enzymes that impact sGC maturation and function., Graphical abstract Image 1, Highlights • The etiology of severe asthma involves airway inflammation and inherent drivers that remain ill-defined. • Airway smooth muscle cells of severe asthmatics display a NO-unresponsive and dysfunctional sGC which persists in culture. • Their inherent sGC dysfunction is associated with low CYB5R3 expression and altered expression of other redox enzymes. • That airway sGC dysfunction and redox enzyme changes cluster within severe asthma is unexpected and may help guide therapy.

Significance Odorant sensing GPCRs are the largest gene family in the human genome. We previously found multiple olfactory receptors and their obligate downstream effectors expressed in the smooth muscle of human bronchi. However, the extent to which odorant-sensing receptors (and the ligands to which they respond) on airway smooth muscle (ASM) are physiologically relevant is not established. Here we show that a monoterpene nerol activates the odorant receptor OR2W3 to relax ASM in both cell and tissue models. Surprisingly, the mechanism of action of OR2W3-mediated ASM relaxation involves paradoxical increases in [Ca2+]i that invoke a cooperative activation of TMEM16A and CFTR to compartmentalize calcium and regulate excitation-contraction coupling in human ASM cells., The recent discovery of sensory (tastant and odorant) G protein-coupled receptors on the smooth muscle of human bronchi suggests unappreciated therapeutic targets in the management of obstructive lung diseases. Here we have characterized the effects of a wide range of volatile odorants on the contractile state of airway smooth muscle (ASM) and uncovered a complex mechanism of odorant-evoked signaling properties that regulate excitation-contraction (E-C) coupling in human ASM cells. Initial studies established multiple odorous molecules capable of increasing intracellular calcium ([Ca2+]i) in ASM cells, some of which were (paradoxically) associated with ASM relaxation. Subsequent studies showed a terpenoid molecule (nerol)-stimulated OR2W3 caused increases in [Ca2+]i and relaxation of ASM cells. Of note, OR2W3-evoked [Ca2+]i mobilization and ASM relaxation required Ca2+ flux through the store-operated calcium entry (SOCE) pathway and accompanied plasma membrane depolarization. This chemosensory odorant receptor response was not mediated by adenylyl cyclase (AC)/cyclic nucleotide-gated (CNG) channels or by protein kinase A (PKA) activity. Instead, ASM olfactory responses to the monoterpene nerol were predominated by the activity of Ca2+-activated chloride channels (TMEM16A), including the cystic fibrosis transmembrane conductance regulator (CFTR) expressed on endo(sarco)plasmic reticulum. These findings demonstrate compartmentalization of Ca2+ signals dictates the odorant receptor OR2W3-induced ASM relaxation and identify a previously unrecognized E-C coupling mechanism that could be exploited in the development of therapeutics to treat obstructive lung diseases.

Glucocorticoids (GCs) and β2-adrenergic receptor (β2AR) agonists improve asthma outcomes in most patients. GCs also modulate gene expression in human airway smooth muscle (HASM), thereby attenuating airway inflammation and airway hyperresponsiveness that define asthma. Our previous studies showed that the pro-fibrotic cytokine, transforming growth factor- β1 (TGF-β1) increases phosphodiesterase 4D (PDE4D) expression that attenuates agonist-induced levels of intracellular cAMP. Decreased cAMP levels then diminishes β2 agonist-induced airway relaxation. In the current study, we investigated whether glucocorticoids reverse TGF-β1-effects on β2-agonist-induced bronchodilation and modulate pde4d gene expression in HASM. Dexamethasone (DEX) reversed TGF-β1 effects on cAMP levels induced by isoproterenol (ISO). TGF-β1 also attenuated G protein-dependent responses to cholera toxin (CTX), a Gαs stimulator downstream from the β2AR receptor. Previously, we demonstrated that TGF-β1 treatment increased β2AR phosphorylation to induce hyporesponsiveness to a β2 agonist. Our current data shows that expression of grk2/3, kinases associated with attenuation of β2AR function, are not altered with TGF-β1 stimulation. Interestingly, DEX also attenuated TGF-β1-induced pde4d gene expression. These data suggest that steroids may be an effective therapy for treatment of asthma patients whose disease is primarily driven by elevated TGF-β1 levels.

This study compared the acute physiological responses of traditional and practical blood flow restriction resistance exercise (tBFR and pBFR, respectively) and high- and low-load resistance exercise without BFR (HL and LL, respectively), as well as the potential sex differences within the aforementioned exercise methods. Fourteen men and fifteen women randomly completed the following experimental conditions: (1) tBFR, consisting of four sets of 30-15-15-15 repetitions of the bilateral horizontal leg press and knee extension exercises, at 30% of one-repetition maximum (1-RM), with a 13.5 cm wide pneumatic cuff placed at the most proximal portion of each thigh and inflated to a pressure equivalent to 50% of the participant’s total occlusion pressure; (2) pBFR, which was the same as the tBFR condition, except that an elastic band wrapped around the proximal portion of each thigh at a tightness of 7 on a 0 to 10 perceived pressure scale was used to reduce blood flow; (3) LL, same as the tBFR and pBFR protocols, except that no BFR was applied; and (4) HL, consisting of 3 sets of 10 repetitions at 80% of 1-RM, with the same 1-min rest interval between sets and a 3-min rest period between exercises. At baseline, immediately post-, 5 min post-, and 15 min post-exercise, whole-blood lactate (WBL), indices of muscle swelling (muscle thickness and thigh circumference), hematocrit and plasma volume changes, were measured as well as superficial electromyography (sEMG) amplitude during exercise. There were no significant (p > 0.05) differences between the tBFR and pBFR exercise protocols for any of the physiological parameters assessed. However, significantly greater (p < 0.05) WBL and sEMG values were observed for HL compared to the remaining exercise conditions. Finally, males displayed greater WBL levels than females at 15 min post-exercise. Interestingly, males also displayed significantly (p < 0.05) greater sEMG amplitude than females within the low-load trials during leg press, but no significant (p < 0.05) sex differences were observed during knee extension. In conclusion, tBFR and pBFR seemed to be capable of inducing the same acute physiological responses. Furthermore, males displayed greater responses than females for some of the physiological parameters measured.

Rationale: Th2 and Th17 cells contribute to airway remodeling, facilitate mucus secretion and increase airway hyperresponsiveness. CD6, a T cell co-stimulatory receptor, interacts with CD166 (ALCAM) and CD318 to modulate activation. We examined whether severe asthma subjects have increased CD6+ cells, the lung inflammatory environment alters CD166 or CD318 expression, and CD6 exposure of airway smooth muscle (ASM) modulates bronchomotor tone. Methods: Lungs (asthma, non-asthma, n=4/group) were lavaged and lymphocytes examined for CD6 by flow cytometry. Tissue was stained for CD166, CD318, CD3, and CD6. ASM stimulated with carbachol (Cch) or CD6-beads was examined for phosphorylation of myosin light chain (pMLC), paxillin (pPax), or cofilin (pCof). ASM were co-cultured with T cells ± IL-33 with CD166 and CD318 expression assessed. Results: Flow analysis showed no difference in CD6+ lavage cells from asthma vs. non-asthma donors. Tissue sections had large differences in lymphocyte number and CD3+/CD6+ cells, with CD166 and CD318 expression on ciliated and basal cells. ALCAM, but not cd318, expression increased in asthma ASM. CD6-coated beads increased pCof and pPax, but not pMLC, to similar levels to Cch. ASM co-cultured with differentiated Th1 cells showed decreased CD166, but not CD318 expression. Co-stimulation with Th1 cells + IL-33 markedly decreased ASM CD166 and CD318 expression. Conclusions: We demonstrate that CD6+ lymphocytes are significantly increased in fatal asthma lung tissue. Furthermore, CD6+ lymphocytes may modulate bronchomotor tone through actin cytoskeletal rearrangements in HASM, and that the inflammatory environment may influence CD6-dependent changes in bronchomotor tone.

The purpose of the current investigation was to compare the acute perceptual responses during low-load resistance exercise (RE) with clinical blood flow restriction (cBFR-RE) and practical blood flow restriction (pBFR-RE), and during conventional low- (LL-RE) and high-load resistance exercise (HL-RE), to determine if these responses differed between young males and females. Twenty-nine participants (14 males: 23.6±2.7years, 25.3±3.1kg/m2 and 15 females: 20.3±1.6years, 23.4±1.9kg/m2) completed the following exercise conditions in a randomized design: 1) cBFR-RE, 2) pBFR-RE, 3) HL-RE, and 4) LL-RE. Low-load conditions consisted of 30-15-15-15 repetitions of two-leg press (LP) and knee extension (KE) exercises with 30% one-repetition maximum (1-RM), and HL-RE consisted of 3 sets of 10 repetitions at 80% 1-RM, all with 60s rest intervals. Ratings of perceived exertion (RPE) and discomfort were assessed before exercise and immediately following each set. RPE was significantly higher in HL-RE compared to all low-load conditions for both exercises after each set (all p

International audience; The spectra of N-ethyl methyl amine, CH3(NH)CH2CH3, were measured using a molecular jet Fourier transform microwave spectrometer in the frequency range of 2 GHz–26.5 GHz. Splittings due to proton inversion tunneling, Coriolis coupling, 14N quadrupole coupling, and methyl internal rotation were fully resolved. The experimentally deduced rotational constants are A = 25 934.717(21) MHz, B = 3919.8212(23) MHz, and C = 3669.530(21) MHz. The proton tunneling causes (+) ↔ (−) splittings of about 1980.9 MHz for all c-type transitions between the lowest symmetric and the higher anti-symmetric energy levels. The splittings of the (+) ← (+) and (−) ← (−) levels, mainly influenced by Coriolis coupling, were also observed and assigned for b-type transitions, yielding the coupling constants Fbc = 0.3409(71) MHz and Fac = 163.9(14) MHz. The 14N quadrupole coupling constants were determined to be χaa = 2.788 65(55) MHz and χbb − χcc = 4.630 45(91) MHz. Fine splittings arising from two inequivalent methyl rotors are in the order of 150 kHz, and the torsional barriers are determined to be 1084.62(41) cm−1 for the CH3NH methyl group and 1163.43(80) cm−1 for the CH2CH3 methyl group. The experimental results are in good agreement with those of quantum chemical calculations.

Rhinovirus (RV) exposure has been implicated in childhood development of wheeze evoking asthma and exacerbations of underlying airways disease. Studies such as the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) and Childhood Origins of ASThma (COAST) have identified RV as a pathogen inducing severe respiratory disease. RVs also modulate airway hyperresponsiveness (AHR), a key characteristic of such diseases. Although potential factors underlying mechanisms by which RV induces AHR have been postulated, the precise mechanisms of AHR following RV exposure remain elusive. A challenge to RV-related research stems from inadequate models for study. While human models raise ethical concerns and are relatively difficult in terms of subject recruitment, murine models are limited by susceptibility of infection to the relatively uncommon minor group (RV-B) serotypes, strains that are generally associated with infrequent clinical respiratory virus infections. Although a transgenic mouse strain that has been developed has enhanced susceptibility for infection with the common major group (RV-A) serotypes, few studies have focused on RV in the context of allergic airways disease rather than understanding RV-induced AHR. Recently, the receptor for the virulent RV-C CDHR3, was identified, but a dearth of studies have examined RV-C-induced effects in humans. Currently, the mechanisms by which RV infections modulate airway smooth muscle (ASM) shortening or excitation-contraction coupling remain elusive. Further, only one study has investigated the effects of RV on bronchodilatory mechanisms, with only speculation as to mechanisms underlying RV-mediated modulation of bronchoconstriction.