Sex differences in anthropometric and cephalometric characteristics in the severity of obstructive sleep apnea syndrome

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Sex differences in anthropometric and

cephalometric characteristics in the severity of

obstructive sleep apnea syndrome

Hung-Huey Tsai,a

Ching-Yin Ho,b

Pei-Lin Lee,c

and Ching-Ting Tand Taipei, Taiwan

Introduction: Craniofacial anatomic abnormalities related to structural narrowing of the upper airway have

been reported in patients with obstructive sleep apnea syndrome (OSAS). The purpose of this study was to test whether there are sex differences in the relative contributions of specific anthropometric and cephalometric measurements of OSAS severity. Methods: The subjects were Taiwanese patients who visited the Ear, Nose, and Throat Department of National Taiwan University Hospital with complaints of snoring or sleep apnea. The anthropometric, cephalometric, and overnight polysomnographic records of 109 subjects were evaluated. Results: There are obvious sex differences in the craniofacial skeletal character-istics that contribute to OSAS severity. Male patients with the following risk factors are likely to have more severe type OSAS: increased neck size, inferiorly positioned hyoid bone, and greater anterior lower facial height. The risk factors related to the severity of OSAS in female patients include smaller posterior facial height and anteriorly positioned hyoid bone. Conclusions: To evaluate OSAS severity, different anthropo-metric and cephaloanthropo-metric measurements should be used for men and women. The craniofacial skeletal characteristics that contribute to OSAS severity were in the anterior lower portion of the profile in men and in the posterior portion of the profile in women. (Am J Orthod Dentofacial Orthop 2009;135:155-64)

S

leep-disordered breathing, characterized by re-peated episodes of hypopnea (underbreathing) and apnea (not breathing) during sleep, affects 24% of middle-aged white men in Wisconsin,1 14.4% of Chinese men in Hong Kong,2and 27% and 16% of middle-aged Korean men and women, re-spectively.3 Obstructive sleep apnea syndrome (OSAS) is a common form of sleep-disordered breathing that is characterized by repetitive episodes of partial or complete upper airway obstruction, causing sleep fragmentation and other symptoms.4 OSAS is equally common among middle-aged white and Hong Kong Chinese populations with a mini-mum prevalence of 4%.1,2

Approximately 40% to 60% of OSAS patients seen in sleep laboratories have hypertension.5,6There is also an association of OSAS with heart failure,7_ischemic heart disease,8stroke,9cardiac arrhythmia,10 and sud-den cardiac death.11 These findings clearly show that OSAS is a serious condition with major health-related consequences and that identification of patients with OSAS is important.

Although still under investigation, increased pha-ryngeal collapse during sleep has been postulated to contribute as a risk factor for OSAS.12,13 Craniofa-cial anatomic abnormalities related to structural nar-rowing of the upper airway have been reported in patients with OSAS.14-20

One overnight polysomnogram in a sleep labora-tory is an adequate measure and is accepted as the gold standard for diagnosis of OSAS. Although the diagnos-tic superiority of polysomnography is without question, it is regarded as both time consuming and expensive. OSAS is a progressive disease that evolves from snoring.21 This evolution moves along a spectrum of heavy snoring with intermittent apneic events, eventu-ally progressing to severe disease with respiratory failure in extreme cases. Early diagnosis of OSAS is important for minimizing neurocognitive, cardiac, be-havioral, and developmental complications as a result of the syndrome.22 _{Therefore, there is a need for a}

a

Professor, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.

b

Associate professor, Department of Otolaryngology, Taipei Veterans General Hospital, Taipei, Taiwan.

c

Lecturer, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

d

Assistant professor, Department of Otolaryngology, National Taiwan Univer-sity Hospital and National Taiwan UniverUniver-sity College of Medicine, Taipei, Taiwan.

Reprint requests to: Ching-Ting Tan, Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7 Chung-Shan South Rd, Taipei 100, Taiwan, ROC; e-mail,

[email protected].

Submitted, November 2006; revised and accepted, October 2008. 0889-5406/$36.00

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simple, rapid, and effective diagnostic tool that can be used to differentiate patients with simple snoring from those with OSAS. Several methods exploiting ad-vanced technologies have been used to evaluate the anatomic characteristics of the upper airway and the craniofacial structures that might predict OSAS and determine the sites of obstruction.23-27 _{However, the} traditional cephalometric method has been the most practical.14,15,18,19,28-32

Although OSAS is prevalent in both sexes, male predominance is clear.1,33_{The mechanism for the sex} difference in OSAS prevalence is an area of intensive research. We hypothesized that the etiology and features of OSAS progression in women differ from those observed in men. This study was conducted to evaluate the potential sex differences in anthropo-metric and cephaloanthropo-metric variables that predict risks associated with OSAS severity.

MATERIAL AND METHODS

The subjects were Taiwanese patients who visited the Ear, Nose, and Throat Department of National Taiwan University Hospital with complaints of snoring or sleep apnea. Institutional review board approval for the study was obtained from National Taiwan Univer-sity Hospital, and all patients gave informed consent before entering the study.

All subjects had a full complement of permanent teeth (except for the third molars in some cases), no apparent craniofacial deformities, no history of orth-odontic treatment, no history of pharyngeal airway surgery, and clinically acceptable symmetry of the dental arches. Anthropometric, polysomnographic, and cephalometric records for 109 subjects (76 men, 33 women) were used.

Anthropometric variables included age; body mass index (BMI), calculated by dividing weight (kg) by height squared (m2_{); and neck size (cm),} measured as the neck circumference at the level of the cricothyroid membrane.

The sleep functions of patients were evaluated from overnight polysomnography. Apnea was de-fined as cessation of breathing for at least 10 sec-onds. Hypopnea is a decreased effort to breathe of at least 50% less than the baseline and with at least a 4% decrease in oxygen saturation. The respiratory disturbance index (RDI) was calculated as the sum of total events (apnea and hypopnea) per hour ([apnea ⫹ hypopnea]/sleep time). A diagnosis of OSAS was based on the RDI. OSAS is considered to be an RDI value of more than 5 per hour. The men and women were divided into 4 groups according to their RDI

values. Subjects who snored but had an RDI less than 5 were grouped into the simple-snoring (Si-Sn) group. The severity of OSAS was stratified by the RDI, with mild (Mi-OSAS) considered 5 to 20 per hour, moderate (Mo-OSAS) 21 to 40 per hour, and severe (Se-OSAS) more than 40 per hour.

A standard cephalometric radiograph was ob-tained for each subject with the teeth in centric occlusion and the Frankfort horizontal plane parallel to the floor at the end of the expiration phase and without swallowing. All cephalometric landmarks were located and digitized by the same investigator (H.-H.T.), with customized software developed for the 2-dimensional morphologic analysis of the anat-omy. Definitions of landmarks, reference planes, and cephalometric angular and linear measurements are given in Figure 1. Errors in landmark identification and digitizing method were estimated by examining duplicate tracings of 20 randomly selected patients made 10 days after the originals. Reliability was fairly accurate, with paired t tests indicating no significant differences in the duplicate measure-Fig 1. Anatomic landmark points: 1, sella turcica (S); 2,

nasion (N); 3, porion (Po); 4, orbitale (Or); 5, posterior nasal spine (PNS); 6, anterior nasal spine (ANS); 7, Point A (A); 8, Point B (B); 9, incisal tip of the maxillary central incisor with the most anteriorly positioned crown (U1); 10, incisal tip of the mandibular central incisor with the most anteriorly positioned crown (L1); 11, gnathion (Gn); 12, menton (Me); 13, gonion (Go); 14, posterior gonion (GoP); 15, lower gonion (GoL); 16, basion (Ba); 17, articulare (Ar); 18, third vertebra (C3); 19, hyoidale (H).

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ments. The reference points were digitized as coor-dinates by using customized software. The straight line passing through sella turcica and parallel to the Frankfort horizontal plane was designated the x-axis. The straight line vertical to the x-axis and passing at a right angle through sella was designated the y-axis. Mean values of the x and y coordinates of all reference points as well as means and standard deviations for all measurements were calculated to enable characterization of the sample groups. All measurements were adjusted for magnification fac-tors.

The Student t test for independent samples was used to compare the sexes. Intergroup mean differ-ences for each measurement were separately as-sessed by using analysis of variance (ANOVA), between the 4 groups of subjects. ANOVA was followed by the Dunnett multiple comparisons test. Stepwise regression analysis was used to determine which variables could be included in a regression model. This procedure is useful in isolating a subset of predictor variables that best explain variations in the dependent variable. All regression analyses were done separately for men and women to assess the relative contributions of the various factors to the RDI. To determine whether the variables identified by the regression model differentiated the 4 groups, a discriminant analysis was performed. This proce-dure develops a discriminant model that attempts to classify each observation into 1 of the 4 groups. All

statistical analyses were performed with the SPSS statistical software package (version 13.0, SPSS, Cary, NC), and a 5% level of significance (P⬍ 0.05) was used.

RESULTS

The numbers of men in the Si-Sn, Mi-OSAS, Mo-OSAS, and Se-OSAS groups were 14, 29, 20, and 13, respectively; the numbers of women were 9, 14, 10, and 0, respectively. Therefore the comparisons of the mean values between the sexes were shown only for the Si-Sn, Mi-OSAS, and Mo-OSAS groups.

The anthropometric data are presented in Table I. Neck size and BMI statistically significantly increased with te severity of OSAS in both sexes. In comparisons with the Si-Sn group, the BMI in both sexes, and the neck size in women were significantly greater in the Mo-OSAS group. The neck sizes of the 3 OSAS groups in men were significantly greater than in the Si-Sn group. The neck sizes of men were significantly greater than those of the women in all groups.

Comparisons of the mean values of cephalomet-ric measurements are shown inTables IIandIII. The angular measurement, SN to FH, in men statistically significantly increased with the severity of OSAS, whereas C3-H-Me in men decreased with the sever-ity of OSAS. There were no statistical differences in any angular measurements between the sexes in the Si-Sn group; however, with the severity of OSAS, SN to FH, the gonial angle, and C3-H-Me in women

Table I. Demographic and anthropometric data

Group variable

Si-Sn Mi-OSAS Mo-OSAS Se-OSAS

ANOVA

Mean SD Mean SD Mean SD Mean SD

RDI M 2.42 1.33 12.82* 4.36 25.95* 4.79 60.65* 21.58 P⬍0.001 F 1.36 1.55 9.57* 3.78 33.72* 5.00 P⬍0.001 T test NS P⫽ 0.022 P⬍0.001 Age M 41.07 10.55 40.81 9.08 42.15 8.99 42.24 10.18 NS F 37.73 9.17 38.50 12.37 43.00 6.39 NS T test NS NS NS BMI M 24.43 2.78 25.56 2.55 26.80* 2.17 26.70* 2.33 P⫽ 0.029 F 21.91 4.56 22.09 2.74 28.20* 2.14 P⬍0.001 T test NS P⬍0.001 NS Neck size M 37.95 1.17 39.02* 1.67 39.90* 1.60 40.71* 1.34 P⬍0.001 F 32.78 1.89 33.50 2.66 36.00* 2.73 P⫽ 0.013 T test P⬍0.001 P⬍0.001 P⬍0.001

M, Male; F, female; NS, not significant.

T test, comparison between male and female subjects. ANOVA, comparison between the Si-Sn and the treatment groups. *Statistically significant difference between the Si-Sn and the treatment groups.

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became greater than those measurements in men. There were some differences in linear measurements from the results of the ANOVA between the sexes; ANS-Me and H⬜C3-Me in men and ANS-PNS and H-C3 in women statistically significantly increased with the severity of OSAS, and S-Go in women statistically significantly decreased with the severity of OSAS. H⬜MP was the only linear measurement that statistically significantly increased with the se-verity of OSAS in both sexes.

To compare craniofacial differences between the sexes in the Si-Sn and Mo-OSAS groups, between the Si-Sn and Se-OSAS groups in men, and between the Si-Sn and Mo-OSAS groups in women, the mean positions of each landmark were plotted, connected, and superimposed (Figs 2-5). These provide profile patterns that can readily be compared with and illustrate the relative overall differences between the 2 groups.

The results of the stepwise multiple regression analy-sis are shown inTable IVwith P values and regression

Table II. Comparison of means of cephalometric angular measurements

Angular measurement (°)

ANOVA

Y-axis M 64.29 4.35 66.15 2.94 65.19 3.24 67.42 4.61 NS F 66.26 2.97 63.75 5.91 63.52 2.70 NS T test NS NS NS SN to FH M 5.29 3.08 4.32 2.85 5.24 3.37 3.38 2.93 NS F 5.34 3.22 9.28* 4.51 10.28* 2.75 P⫽ 0.017 T test NS P⬍0.001 P⬍0.001 PP to FH M 5.49 4.13 4.72 4.06 4.64 2.28 4.21 3.21 NS F 2.90 2.26 0.59 3.39 0.84 2.89 NS T test NS P⫽ 0.002 P⬍0.001 MP to FH M 26.06 7.85 28.67 5.35 27.12 6.69 30.39 9.25 NS F 31.12 3.91 29.33 9.96 29.52 3.87 NS T test NS NS NS RP to FH M 88.76 5.89 90.31 4.70 90.32 3.32 92.34 4.83 NS F 91.32 4.23 86.99 8.68 87.50 5.19 NS T test NS NS NS SNA M 81.64 6.02 81.21 3.21 83.15 3.37 81.65 3.73 NS F 81.53 4.85 81.09 5.05 80.04 5.27 NS T test NS NS NS SNB M 79.04 3.51 79.43 2.64 79.26 4.45 79.32 4.43 NS F 78.78 4.71 77.44 6.04 77.34 3.06 NS T test NS NS NS Gonial angle M 116.29 8.85 118.34 7.07 116.80 5.97 118.07 7.66 NS F 119.82 3.90 122.31 5.61 124.04 4.18 NS T test NS NS P⫽ 0.002 N-S-Ba M 129.71 4.00 126.99 5.24 129.26 5.00 126.53 5.05 NS F 126.48 4.17 129.22 6.78 132.20 4.97 NS T test NS NS NS C3-H-Me M 163.54 11.96 162.67 11.04 160.56 13.32 149.78* 17.95 P⫽ 0.024 F 159.97 10.60 159.34 18.61 170.50 7.87 NS T test NS NS P⫽ 0.039

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coefficients. The variables entered into the model were H⬜MP, y-axis, N-ANS, neck size, H-C3, and Go-Me in men, and BMI, S-Ba, H-C3, S-Go, and Go-Me in women. R2 _{values for these variables were 0.688 for men and}

0.931 for women. In the discriminant analysis between the 4 groups (3 groups of women) for all cases, about 60% of the men and more than 85% of the women were correctly classified (Table V).

Table III. Comparison of means of cephalometric linear measurements

Linear

measurement (mm)

ANOVA

N-S M 65.64 2.53 65.28 2.99 65.44 3.21 65.52 3.25 NS F 62.68 2.35 61.66 2.49 63.62 2.78 NS T test P⫽ 0.010 P⬍0.001 NS N-ANS M 54.87 2.26 54.38 2.69 53.82 3.38 53.50 2.98 NS F 51.41 3.38 49.11 3.29 50.10 3.55 NS T test P⫽ 0.008 P⬍0.001 P⫽ 0.009 ANS-Me M 65.25 5.03 69.22* 5.35 69.54* 4.65 71.02 6.31 P⫽ 0.034 F 66.97 6.17 66.27 4.66 66.54 3.98 NS T test NS NS NS N-Me M 118.26 5.41 122.21 6.06 121.45 6.76 122.90 8.39 NS F 116.94 8.23 111.55 6.49 114.12 6.17 NS T test NS P⬍0.001 P⫽ 0.008 S-Go M 81.20 6.35 82.30 5.90 81.99 4.60 83.38 4.95 NS F 75.18 5.47 69.52* 4.05 68.58* 5.35 P⫽ 0.012 T test P⫽ 0.029 P⬍0.001 P⬍0.001 ANS-PNS M 50.19 2.12 48.70 3.52 50.41 3.73 48.59 3.39 NS F 45.44 1.80 46.21 3.43 48.74* 1.61 P⫽ 0.021 T test P⬍0.001 P⫽ 0.034 NS Go-Me M 68.10 3.60 68.86 4.77 70.01 5.10 68.79 3.45 NS F 66.23 3.15 63.74 3.26 65.42 3.50 NS T test NS P⬍0.001 P⫽ 0.017 Ar-Go M 48.51 5.07 48.77 5.33 48.60 3.05 48.19 3.39 NS F 43.93 4.85 39.89 3.07 42.14 4.23 NS T test P⫽ 0.043 P⬍0.001 P⬍0.001 S-Ba M 44.85 3.36 45.38 2.32 45.32 3.40 45.85 4.24 NS F 42.10 1.61 41.91 2.24 40.50 1.64 NS T test P⫽ 0.033 P⬍0.001 P⬍0.001 H-C3 M 39.39 3.43 37.87 3.85 40.19 3.69 38.62 4.17 NS F 32.67 2.42 32.80 2.73 36.62* 3.22 P⫽ 0.004 T test P⬍0.001 P⬍0.001 P⫽ 0.015 H⬜MP M 13.08 4.05 15.48 3.86 17.15* 4.71 20.75* 6.83 P⬍0.001 F 7.83 5.31 12.41 6.07 15.18* 3.97 P⫽ 0.018 T test P⫽ 0.014 P⫽ 0.050 NS H⬜C3-Me M 5.14 3.91 4.99 4.29 6.67 4.05 9.74* 7.11 P⫽ 0.025 F ⫺2.11 6.84 1.44 4.16 3.18 2.84 NS T test P⫽ 0.004 P⫽ 0.014 P⫽ 0.022

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DISCUSSION

Although the RDI value of the women was signif-icantly smaller than that of the men in the Mi-OSAS group and no woman was in the Se-OSAS group, the RDI value of the women was significantly greater than that of the men in the Mo-OSAS group. It was supposed that there might be sex differences in the progression of OSAS in a Taiwanese population.

There were no significant differences in mean ages among the groups for either sex or between⬎men and women for the Si-Sn, Mi-OSAS, Mo-OSAS groups. It is thought that there are no sex differences in age for the likelihood of having OSAS.

Obesity has been thought to be a primary cause of OSAS. Obesity might be related to OSAS because of excessive soft tissue in the upper airway. Our study also Fig 2. Craniofacial differences between the sexes in the Si-Sn group.

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demonstrated that BMI and neck size statistically sig-nificantly increased with the severity of OSAS in both sexes. Male and female subjects differed in that the men in the Mi-OSAS group had a larger neck size. Ryan and Love34 _{showed that obese patients with} large necks tend to have a more easily collapsible velopharynx during wakefulness. The airway has a tendency to collapse from negative pressure

associ-ated with inspiration and airflow. The muscle tone of the palate, pharynx, and tongue help to balance the patency. Mass loading on the airway can produce changes in the airway configuration and its function. Cervical fat can produce a gravitational loading effect on the airway, especially when patients are supine. Obesity, through fat deposits around the upper airway in the neck, might narrow the pharynx and alter its Fig 4. Craniofacial differences between the Si-Sn and Se-OSAS groups in men.

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shape and mechanical properties, predisposing patients to sleep-related obstruction. Our results indicated that large BMI and neck size, especially in men, are risk factors associated with OSAS severity.

Certain forms of craniofacial anatomic defects, including inferior displacement of the hyoid bone, larger gonial angle, smaller anterior cranial base, altered anterior and posterior facial heights, and mandibular deficiency, have been suggested as pre-disposing factors for upper airway obstruction during sleep.28,35-39 _{It was shown that the hyoid bone} positions relative to the mandible and the third vertebrae were different between men and women in the Si-Sn group. The distances from the hyoid bone to the third vertebrae and to the mandible in men were both statistically significantly greater (anteri-orly and inferi(anteri-orly) than those in women. Although

both female and male OSAS subjects had an inferi-orly positioned hyoid bone compared with Si-Sn subjects, the changes of the hyoid bone positions as OSAS becomes severe were different between men and women. The position of the hyoid bone becomes more inferior as the condition becomes more severe, from Si-Sn to Se-OSAS, especially in men. In female patients, the position of the hyoid bone becomes more anterior as the OSAS condition becomes more severe.

The lingual musculature plays a strategic role in maintaining upper airway patency and is, moreover, anchored to the hyoid bone.40,41 _{An inferiorly} posi-tioned hyoid bone can be due to macroglossia, diffuse fat depositions, or relaxation of the lingual musculature. These conditions might cause the man-dibular opening, making the gonial angle increase and altering anteroposterior facial height ratios. Therefore, an inferiorly positioned hyoid bone can impair upper airway patency because of involvement of the lingual musculature.

In addition to an inferiorly positioned hyoid bone, greater lower facial height was also related to an overall increase in OSAS severity in men, whereas larger SN to FH angle, smaller posterior facial height, and anteriorly positioned hyoid bone were related to an overall in-crease in OSAS severity in women. Based on results of the regression analysis, the following anthropometric and cephalometric characteristics are most likely to be expected in patients with severe OSAS: increased neck size and inferiorly positioned hyoid bone in both sexes, larger y-axis in men, and smaller posterior facial height and anteriorly positioned hyoid bone in women. From superimposition of the profiles of the Si-Sn and OSAS groups, it is clear that the major differences between these groups were in the anterior lower portion in men (inferiorly positioned chin and hyoid bone) and in the posterior portion in women (smaller posterior facial height). A larger y-axis implies more downward man-dibular growth and is related to greater lower facial height. A smaller posterior facial height implies man-dibular ramus deficiency and is related to a larger gonial angle and altered anterior and posterior facial heights.

Table IV shows that H-C3 (the distance from the third vertebra to the hyoid bone) had a negative correlation with the RDI in men and a positive corre-lation with the RDI in women. Previous studies showed that, although the hyoid bone position is associated with head posture, there is a regular pattern of down-ward and slightly anterior descent of the hyoid through-out the growth period.42,43_{The role of the hyoid bone} in the evolution of OSAS might differ between the

Table IV. Stepwise multiple regression analysis

Variable Regression coefficient P value

Men Constant ⫺114.638 0.114 H⬜MP 1.906 ⬍0.001 Y-axis 1.671 0.007 N-ANS ⫺2.580 0.002 Neck size 3.268 0.022 H-C3 ⫺1.507 0.024 Go-Me 0.957 0.090 R⫽ 0.688, R2_{⫽ 0.473,} adjusted R2_{⫽ 0.418} Women Constant 0.586 0.985 BMI 0.289 0.490 S-Ba ⫺0.420 0.602 H-C3 3.441 ⬍0.001 S-Go ⫺1.853 ⬍0.001 Go-Me 0.632 0.166 R⫽ 0.931, R2_{⫽ 0.866,} adjusted R2_{⫽ 0.832}

Table V. Discriminant analysis (data are numbers of patients)

Original group

classification n

Discriminant analysis classification (%)

Men Si-Sn 14 11 (78.6) 3 (21.4) 0 (0) 0 (0) Mi-OSAS 29 6 (20.7) 15 (51.7) 5 (17.3) 3 (10.3) Mo-OSAS 20 1 (5.0) 4 (25.0) 11 (55.0) 3 (15.0) Se-OSAS 13 0 (0) 1 (7.7) 2 (15.4) 10 (76.9) Women Si-Sn 9 7 (77.8) 2 (22.2) 0 (0) Mi-OSAS 14 2 (14.3) 12 (85.7) 0 (0) Mo-OSAS 10 0 (0) 0 (0) 10 (100)

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sexes. Further investigation in this area could help to clarify these issues.

CONCLUSIONS

There are obvious sex differences in the cranio-facial skeletal characteristics that contribute to OSAS severity and, to evaluate OSAS severity, different anthropometric and cephalometric measure-ments should be used for men and women.

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