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Growth hormone (GH) receptor (GHR) is abundantly expressed in neurons that co‐release the agouti‐related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). Since ARHAgRP/NPY neurons regulate several hypothalamic–pituitary‐endocrine axes, this neuronal population possibly modulates GH secretion via a negative feedback loop, particularly during food restriction, when ARHAgRP/NPY neurons are highly active. The present study aims to determine the importance of GHR signaling in ARHAgRP/NPY neurons on the pattern of GH secretion in fed and food‐deprived male mice. Additionally, we compared the effect of two distinct situations of food deprivation: 16 h of fasting or four days of food restriction (40% of usual food intake). Overnight fasting strongly suppressed both basal and pulsatile GH secretion. Animals lacking GHR in ARHAgRP/NPY neurons (AgRP∆GHR mice) did not exhibit differences in GH secretion either in the fed or fasted state, compared to control mice. In contrast, four days of food restriction increased GH pulse frequency, basal GH secretion, and pulse irregularity/complexity (measured by sample entropy), whereas pulsatile GH secretion was not affected in both control and AgRP∆GHR mice. Hypothalamic Ghrh mRNA levels were unaffected by fasting or food restriction, but Sst expression increased in acutely fasted mice, but decreased after prolonged food restriction in both control and AgRP∆GHR mice. Our findings indicate that short‐term fasting and prolonged food restriction differentially affect the pattern of GH secretion, independently of GHR signaling in ARHAgRP/NPY neurons. [ABSTRACT FROM AUTHOR]

BackgroundOSA pathogenesis is complex and may vary according to ethnicity. The anatomic component predisposing to OSA is the result of the interaction between bony structure and upper airway soft tissues and can be assessed using passive critical closing pressure (Pcrit). We hypothesized that Japanese-Brazilians and whites present different predictors of upper airway collapsibility, suggesting different causal pathways to developing OSA in these two groups.MethodsMale Japanese-Brazilians (n = 39) and whites (n = 39) matched for age and OSA severity were evaluated by full polysomnography, Pcrit, and upper airway and abdomen CT scans for determination of upper airway anatomy and abdominal fat, respectively.ResultsPcrit was similar between the Japanese-Brazilians and the whites (-1.0 ± 3.3 cm H2O vs -0.4 ± 3.1 cm H2O, P = .325). The Japanese-Brazilians presented smaller upper airway bony dimensions (cranial base, maxillary, and mandibular lengths), whereas the whites presented larger upper airway soft tissue (tongue length and volume) and a greater imbalance between tongue and mandible (tongue/mandibular volume ratio). The cranial base angle was associated with Pcrit only among the Japanese-Brazilians (r = -0.535, P < .01). The tongue/mandibular volume ratio was associated with Pcrit only among the whites (r = 0.460, P < .01). Obesity-related variables (visceral fat, BMI, and neck and waist circumferences) showed a similar correlation with Pcrit in the Japanese-Brazilians and the whites.ConclusionsJapanese-Brazilians and whites present different predictors of upper airway collapsibility. Although craniofacial bony restriction influenced Pcrit only in the Japanese-Brazilians, an anatomic imbalance between tongue and mandible volume influenced Pcrit among the whites. These findings may have therapeutic implications regarding how to improve the anatomic predisposition to OSA across ethnicities.

Study objectivesUpper airway anatomy plays a major role in obstructive sleep apnea (OSA) pathogenesis. An inferiorly displaced hyoid as measured by the mandibular plane to hyoid distance (MPH) has been consistently associated with OSA. The hyoid is also a common landmark for pharyngeal length, upper airway volume, and tongue base. Tongue dimensions, pharyngeal length, and obesity are associated with OSA severity, although the link between these anatomical variables and pharyngeal collapsibility is less well known. We hypothesized that obesity as measured by body mass index (BMI), neck and waist circumferences, and variables associated with hyoid position (pharyngeal length, upper airway volume, and tongue dimensions) would be associated with passive pharyngeal critical closing pressure (Pcrit).DesignCross-sectional.SettingAcademic hospital.Patients34 Japanese-Brazilian males age 21 to 70 y.InterventionsN/A.Measurements and resultsWe performed computed tomography scans of the upper airway, overnight polysomnography, and Pcrit measurements in all subjects. On average, subjects were overweight (BMI = 28 ± 4 kg/m(2)) and OSA was moderately severe (apnea-hypopnea index = 29 [13-51], range 1-90 events/h). Factor analysis identified two factors among the studied variables: obesity (extracted from BMI, neck and waist circumferences) and hyoid position (MPH, pharyngeal length, tongue length, tongue volume, and upper airway volume). Both obesity and hyoid position correlated with Pcrit (r = 0.470 and 0.630, respectively) (P < 0.01). In addition, tongue volume, tongue length, pharyngeal length, and MPH correlated with waist and neck circumferences (P < 0.05).ConclusionsPharyngeal critical closing pressure is associated with obesity and hyoid position. Tongue dimensions, pharyngeal length, and the mandibular plane to hyoid distance are associated with obesity variables. These findings provide novel insight into the potential factors mediating upper airway collapse in obstructive sleep apnea.

Signal disruptions in small animals during the realization of the Forced Oscillation Technique are a well-known cause of data loss as it leads to non-reliable estimations of the respiratory impedance. In this work, we assessed the effects of removing the disrupted epoch when a 3-seconds input signal composed of one and a half 2-seconds full cycle is used. We tested our hypothesis in 25 SAMR1 mice under different levels of bronchoconstriction due to methacholine administration by iv bolus injections in different doses (15 animals) and by iv continuous infusion in different infusion rates (10 animals). Signal disruptions were computationally simulated as sharp drops in the pressure signal within a short timescale, and signal processing was performed using own developed algorithms. We found that the model goodness of fit worsens when averaging techniques to estimate the input respiratory impedance are not used. However, no statistically significant differences were observed in the comparison between Constant Phase Model parameters of the full 3-s signal and the 2-s non disrupted epoch in all doses or infusion rates for both methacholine delivery strategies. The proposed technique presents reliable outcomes that can reduce animal use in Forced Oscillation Technique realization. [ABSTRACT FROM AUTHOR]

Determining the presence of thoracoabdominal asynchrony in chronic obstructive pulmonary disease (COPD) patients is clinically relevant, but there is no consensus on the optimal parameters for performing this analysis. We assessed 22 COPD patients (FEV1 40 ± 10% predicted) and 13 healthy controls during rest and exercise with optoelectronic plethysmography (70% maximum workload) on a cycle ergometer. Thoracoabdominal asynchrony was calculated by using phase angle and phase shift parameters following a three-compartment model involving the upper and lower rib cages and abdomen. Patients were classified as having thoracoabdominal asynchrony (TAA+) or not (TAA-) based on control values (mean ± 2 SDs). The chest wall volume and compartmental contribution were also measured. Thoracoabdominal asynchrony was observed in the lower rib cage. The phase angle detected more TAA+ patients at rest (15 vs. 7 patients) and during exercise (14 vs. 8 patients) compared with the phase shift. TAA+ patients also presented a lower chest wall volume, lower rib cage contribution, and higher abdominal contribution to chest wall volume compared with the control and TAA- patients. Thoracoabdominal asynchrony was more detectable during rest and exercise using the phase angle parameter, and it was observed in the lower rib cage compartment, reducing the chest wall volume during exercise in patients with COPD. NEW & NOTEWORTHY This study contributes to advance the knowledge over the previous lack of consensus on the assessment of thoracoabdominal asynchrony. We rigorously evaluated the related features that interfere in the measurement of the asynchrony (measurement tool, chest wall model and calculation parameter). Our results suggest that phase angle detects more suitably thoracoabdominal asynchrony that occurs on the lower ribcage and leads to a reduction in the chest wall volume during exercise in COPD patients. [ABSTRACT FROM AUTHOR]