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1.
We examined the hypothesis that estradiol (E2) would affect fetal anterior pituitary corticotroph and lactotroph function in vitro, and that any effects would be influenced by gestational age. Anterior pituitary cells from fetal sheep at day 129 (n = 4) and at day 139 (n = 5) of gestation were cultured. After 96 h in culture, cells were treated for 18 h with E2 concentrations ranging from 0 to 1000 nM, in the presence or absence of 100 nM of corticotropin-releasing hormone (CRH), cortisol, arginine vasopressin (AVP), or CRH and cortisol, to examine their effects on corticotroph function. Cells were also treated with bromocriptine or increasing concentrations of E2 to study their effects on lactotroph function. Immunoreactive (ir) adrenocorticotropin (ACTH) and prolactin in the culture medium were measured by radioimmunoassay. Levels of cellular pro-opiomelanocortin (POMC) mRNA and prolactin mRNA were determined by in situ hybridization. Immunohistochemistry was used to determine the percentage of cells that were immunopositive for ACTH (corticotrophs) or prolactin (lactotrophs). ACTH output was stimulated by CRH treatment at day 139 but not at day 129 of gestation, and cortisol attenuated this response. ACTH output by cells cultured with 10 nM E2 and 100 nM CRH, at 139 days of gestation, was greater than with CRH alone (p < 0.05). E2 did not affect basal ACTH output or ACTH output with any other treatment or levels of POMC mRNA. Prolactin output was not affected by E2 treatment. Bromocriptine significantly decreased prolactin output but not levels of prolactin mRNA. We conclude that E2 may affect CRH-stimulated fetal sheep pituitary corticotroph function late in gestation, but only within a narrow, physiological range of concentration.  相似文献   

2.
Corticotrophs were long thought to be a static, homogeneous population of cells that respond positively to hypothalamic stimulation, are inhibited by glucocorticoid feedback and secrete a single biologically active peptide, ACTH(1-39). Our current understanding is that this is an oversimplification and corticotrophs are a dynamic and more complex group of cells. The biosynthetic precursors of ACTH and other cleavage products of proopiomelanocortin (POMC) have been found to be secreted by anterior pituitary cells, to circulate and to have biological activity. POMC and the biosynthetic intermediate, pro-ACTH, exert activity antagonistic to ACTH(1-39) on glucocorticoid secretion by adrenal cells, and other derivatives of POMC are mitogenic to adrenocortical cells. In terms of responses to hypothalamic and peripheral factors, corticotrophs are functionally heterogeneous. This is reflected in the sensitivity of individual subtypes of corticotrophs to CRH, vasopressin and glucocorticoids. There is a functional plasticity amongst the various types of corticotrophs. During gestation, in fetal sheep, changes occur in the overall ACTH-secretory responses to CRH relative to vasopressin, the proportions of total corticotrophs that respond to the respective peptides and the average secretory response of individual cells. Corticotrophs also respond to locally produced pituitary factors. Local actions of leukaemia inhibitory factor are demonstrated by the effects of immunoneutralization of the peptide in pituitary cells. Urocortin and preproTRH(178-199) are locally produced peptides with potent stimulatory and inhibitory actions on corticotrophs, respectively. The specific roles of these peptides are under investigation.  相似文献   

3.

Objectives

To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499mg and ≥500mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension.

Design

Secondary analysis of the Vitamins in Pre-Eclampsia Trial.

Setting

25 UK hospitals in ten geographical areas.

Population

946 women with pre-existing risk factors for pre-eclampsia.

Methods

Women with pre-eclampsia and proteinuria 300-499mg/24h (PE300, referent group, n=60) or proteinuria ≥500 mg/24h (PE500, n=161) were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615) or gestational hypertension (GH, n=110).

Main Outcome Measures

Maternal: progression to severe hypertension. Perinatal: small for gestational age (SGA) <5th centile, gestation at delivery.

Results

Severe hypertension occurred more frequently in PE500 (35%) and PE300 (27%) than CHT (5.9%; P≤0.01) and GH (10%; p≤0.001). Gestation at delivery was earlier in PE500 (33.2w) than PE300 (37.3w; P≤0.001), and later in CHT (38.3w; P≤0.05) and GH (39.1w; P≤0.001). SGA infants were more frequent in PE300 (32%) than in CHT (13.3%; P≤0.001) and GH (16.5%; P≤0.05). Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P≤0.001), and to receive magnesium sulphate (17% vs. 1.7%, P≤0.05).

Conclusion

Women with PE300 have complication rates above those of women managed as out-patients (GH and CHT), meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500.  相似文献   

4.
We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feedforward of fetal hypothalamic-pituitary-adrenal function, leading to birth.  相似文献   

5.
6.
Metabolic profiles of amniotic fluid and maternal blood are sources of valuable information about fetus development and can be potentially useful in diagnosis of pregnancy disorders. In this study, we applied 1H NMR-based metabolic profiling to track metabolic changes occurring in amniotic fluid (AF) and plasma (PL) of healthy mothers over the course of pregnancy. AF and PL samples were collected in the 2nd (T2) and 3rd (T3) trimester, prolonged pregnancy (PP) until time of delivery (TD). A multivariate data analysis of both biofluids reviled a metabolic switch-like transition between 2nd and 3rd trimester, which was followed by metabolic stabilization throughout the rest of pregnancy probably reflecting the stabilization of fetal maturation and development. The differences were further tested using univariate statistics at α = 0.001. In plasma the progression from T2 to T3 was related to increasing levels of glycerol, choline and ketone bodies (3-hydroxybutyrate and acetoacetate) while pyruvate concentration was significantly decreased. In amniotic fluid, T2 to T3 transition was associated with decreasing levels of glucose, carnitine, amino acids (valine, leucine, isoleucine, alanine, methionine, tyrosine, and phenylalanine) and increasing levels of creatinine, succinate, pyruvate, choline, N,N-dimethylglycine and urocanate. Lactate to pyruvate ratio was decreased in AF and conversely increased in PL. The results of our study, show that metabolomics profiling can be used to better understand physiological changes of the complex interdependencies of the mother, the placenta and the fetus during pregnancy. In the future, these results might be a useful reference point for analysis of complicated pregnancies.  相似文献   

7.
Hystrix javanica is endemic species in Indonesia. Study about fetal development of Hystrix javanica are very rare because of sample limitation. This study was carried out to describe the morphometrics and x-ray analysis of three fetuses in different stage to give basic information about fetal development of Hystrix javanica. Three fetus samples fixed in Bouin’s solution was used in this study. Observation was carried out to identify the characteristic of three fetus samples. This included the pattern of hair, body measurements, body volume, and body weight. X-ray analysis was carried out to know the ossification process in the fetal development. Statistical analysis was carried out using Microsoft 365® Excel program software. Three fetus samples had different specific hair pattern, that was hairless, smooth hairs, and smooth hairs with dense-non dense pattern. Body volume of 1st, 2nd, and 3rd fetus were 23mL, 90mL, and 170mL, respectively. Body weight of 1st, 2nd, and 3rd fetus were 19.5g, 79.22g, and 153.18g, respectively. Pearson’s correlation analysis shown strong relationship between total body length, front body length, back body length, horizontal body diameter, vertical body diameter, head length, and head diameter against body volume and body weight of three fetuses. Significant positive correlation was shown between horizontal body diameter, vertical body diameter, and head diameter against body volume and body length with P value < 0.05. Faint radiopaque images showed in the 2nd fetus sample and strong radiopaque images showed in the 3rd fetus sample. Radiopaque images were identified in the teeth, cranium, vertebrae, and extremities bones. In this study we concluded that there was a specific hair pattern in different fetal stage. All body measurements have positive correlation with body volume and body weight and x-ray analysis shown that the ossification of the bone was started to happen while the smooth hair was growth.  相似文献   

8.
The present study was aimed at investigating whether PACAP stimulates accumulation of cAMP, as well as hormonal secretion of homogeneous populations of pituitary proopiomelanocortin (POMC) cells, namely melanotrophs and AtT-20 corticotrophs. PACAP was shown to enhance cAMP accumulation in a dose-dependent fashion in both cell types (with EC50 values of approx. 10(-10) M) and elicited additive increases of cAMP production with CRF in melanotrophs, but not in corticotrophs. PACAP also stimulated dose-dependently the secretion of alpha-MSH and ACTH, with EC50 concentrations of about 10(-9) M. In melanotrophs, bromocriptine significantly depressed PACAP-induced cAMP formation and blunted by more than 90% stimulated alpha-MSH release. This study shows that (1) pituitary POMC cells did respond to PACAP by enhancing cAMP accumulation and elevating hormone secretion as well; (2) the effect of PACAP was additive with CRF on cAMP production in melanotrophs, but not in corticotrophs, while there was no additivity on peptide output from both cell types; (3) activation of dopamine receptors in melanotrophs dampened both cAMP formation and peptide secretion. These findings are consistent with PACAP playing a possible hypophysiotropic role in the regulation of pituitary POMC cell activity.  相似文献   

9.
Pituitary corticotroph ontogeny and regulation in transgenic zebrafish   总被引:4,自引:0,他引:4  
We characterized zebrafish proopiomelanocortin (POMC) gene promoter, and sequence analysis revealed that the promoter contains regulatory elements conserved among vertebrate species. To monitor the ontogeny of the pituitary POMC lineage in living vertebrates, we generated transgenic zebrafish expressing green fluorescent protein (GFP) driven by the POMC promoter. Zebrafish POMC-GFP is first expressed asymmetrically as two bilateral groups of cells most anterior to the neural ridge midline at 18-20 h post fertilization (hpf). POMC-GFP-positive cells then fuse into a single-cell mass within the pituitary anlage after 24 hpf and subsequently organize as distinct anterior and posterior domains between 48 and 64 hpf. Immunohistochemical studies with ACTH and alphaMSH antisera showed that POMC-GFP was mainly targeted to both anterior and posterior pituitary corticotrophs, whereas posterior pituitary region melanotrophs did not express GFP. To determine in vivo zebrafish corticotroph responses, dexamethasone (10(-5) m) was added to live embryos, which selectively suppressed POMC-GFP expression in the anterior group of corticotrophs, suggesting a distinct domain that is responsive to glucocorticoid feedback. Transgenic zebrafish with specific POMC-GFP expression in pituitary corticotrophs offers a powerful genetic system for in vivo study of vertebrate corticotroph lineage development.  相似文献   

10.
Oncofetal aspects of ACTH and pro-opiomelanocortin (POMC)-derived peptides were studied immunohistochemically at the light and electron microscopic level in human fetal pituitary glands, pituitary adenomas, and small-cell carcinoma of the lung. ACTH, beta-endorphin, and gamma-MSH were localized in the same cells of both fetal and adult pituitary, as well as in the above-mentioned neoplastic tissues. However, alpha-MSH was observed only in the early fetal pituitary, its concentration decreasing with advancing gestational age. The adult pituitary contained only a few alpha-MSH-positive cells. By immunoelectron microscopy, ACTH in the adult pituitary was localized exclusively in the secretory granules. In fetal pituitary at 9 weeks' gestation, ACTH was localized in the perinuclear spaces (PNS), cisternae of rough endoplasmic reticulum (RER), Golgi saccules, and secretory granules. The staining pattern of ACTH in these organelles varied from cell to cell. In fetal pituitaries of greater gestational ages, ACTH was localized in secretory granules. The pituitary adenomas mimicked the staining characteristics of the adult pituitary, i.e., negative or only very occasional alpha-MSH staining and localization of ACTH in the secretory granules. The ectopic ACTH-producing tumors showed a staining pattern similar to that of the early fetal pituitary, i.e., positive staining for alpha-MSH and the presence of ACTH in PNS and cisternae of RER.  相似文献   

11.
A synthetic peptide (ST-1) corresponding to the cleavage site between ACTH and beta-lipotropic hormone moieties of murine pro-opiomelanocortin (POMC) was constructed and its polyclonal antibody was generated. This antiserum immunoprecipitated only POMC from extracts of AtT-20 cells. Moreover, an antiserum raised against porcine ACTH immunoprecipitated both ACTH[1-39] and POMC. When ultra-thin frozen sections of melanotrophs in rat pars intermedia were immunolabeled with anti-ST-1 followed by protein A-gold, gold particles indicating the presence of POMC were selectively found in the electron-dense secretory granules in the Golgi area. In addition, the immunolabeling was also observed in the cisternae of the Golgi apparatus and rough endoplasmic reticulum. In contrast, with a polyclonal antibody specific for alpha-melanocyte-stimulating hormone the gold particles were found exclusively in the electron-lucent secretory granules, with none seen in the electron-dense secretory granules. With anti-ACTH serum, gold particles were observed in the electron-dense and -lucent secretory granules. In corticotrophs in the pars distalis, many gold particles indicating the presence of POMC were observed in the Golgi and peripheral secretory granules, but the percentage of immunolabeling in the peripheral secretory granules varied from cell to cell. On the other hand, ACTH immunolabeling was found in almost all the secretory granules. This finding suggests that the processing of POMC in corticotrophs might occur in the relatively peripheral granules. These results suggest that the intracellular sites of POMC processing are somewhat different between melanotrophs and corticotrophs in the pituitary.  相似文献   

12.

Objective

To investigate the association between weekly weight gain, during the second and third trimesters, classified according to the 2009 Institute of Medicine (IOM/NRC) recommendations, and maternal and fetal outcomes.

Methods

Gestational weight gain was evaluated in 2,244 pregnant women of the Brazilian Study of Gestational Diabetes (Estudo Brasileiro do Diabetes Gestacional – EBDG). Outcomes were cesarean delivery, preterm birth and small or large for gestational age birth (SGA, LGA). Associations between inadequate weight gain and outcomes were estimated using robust Poisson regression adjusting for pre-pregnancy body mass index, trimester-specific weight gain, age, height, skin color, parity, education, smoking, alcohol consumption, gestational diabetes and hypertensive disorders in pregnancy.

Results

In fully adjusted models, in the second trimester, insufficient weight gain was associated with SGA (relative risk [RR] 1.72, 95% confidence interval [CI] 1.26–2.33), and excessive weight gain with LGA (RR 1.64, 95% CI 1.16–2.31); in third trimester, excessive weight gain with preterm birth (RR 1.70, 95% CI 1.08–2.70) and cesarean delivery (RR 1.21, 95% CI 1.03–1.44). Women with less than recommended gestational weight gain in the 2nd trimester had a lesser risk of cesarean deliveries (RR 0.82, 95% CI 0.71–0.96) than women with adequate gestational weight gain in this trimester.

Conclusion

Though insufficient weight gain in the 3rd trimester was not associated with adverse outcomes, other deviations from recommended weight gain during second and third trimester were associated with adverse pregnancy outcomes. These findings support, in part, the 2009 IOM/NRC recommendations for nutritional monitoring during pregnancy.  相似文献   

13.
14.
Basophil invasion, i.e., invasion of basophilic corticotrophs from the residual intermediate lobe into the posterior lobe of the human pituitary gland, is believed to be a physiological phenomenon. This study evaluated the distribution of CPE, CPD, CPZ, alpha-MSH, ACTH, and Ki-67 immunoreactivity between human anterior pituitary and basophil invasion of the neurohypophysis. Mild to moderate immunoreactivities for CPE and CPZ were distributed relatively uniformly in the majority of the anterior pituitary cells and basophil invasion. In contrast, only corticotrophs exhibited intense CPD immunoreactivity. Basophil invasion showed similar immunoreactivities for alpha-MSH, ACTH, CPE, and CPZ as corticotrophs in the anterior pituitary, except for CPD, which was detected much less frequently. In the posterior lobe, CPE, CPD, and CPZ were present within the Herring bodies. Although no MIB-1 immunoreactivity was identified in anterior pituitary cells, limited MIB-1 labeling was detected in basophil invasion in five of ten cases. Highly selective expression of CPD in corticotrophs suggests that CPD plays a particularly important role in prohormone (POMC) processing in corticotrophs, with minimal or no significant roles in non-corticotrophs. Evidence that corticotrophs in basophil invasion are undergoing proliferation and are also phenotypically different from their counterpart in the anterior pituitary has further raised the possibility of some neoplastic potential.  相似文献   

15.
B Lutz-Bucher  J M Félix  B Koch 《Peptides》1990,11(6):1183-1189
The present study was aimed at investigating the effect of protein kinase C (PKC) activation on CRF receptor function of proopiomelanocortin (POMC) cells in culture. Incubation of tissues with the phorbol ester PMA selectively potentiated corticotropin-releasing factor (CRF)-stimulated ACTH secretion and cyclic AMP formation of anterior pituitary (AP) cells, while, in sharp contrast, it failed to similarly affect intermediate pituitary (IP) cells and AtT-20 corticotrophs exposed to CRF. Unexpectedly, however, long-term treatment of cultures with PMA, which depletes cell stores of PKC, resulted in a similar dramatic attenuation of stimulated peptide release from both corticotrophs and melanotrophs, while being without significant effect on cyclic AMP production. Exposure of cells to PMA did not change either basal or CRF-enhanced levels of POMC mRNA. We conclude that activation of PKC fails to synergize with CRF-mediated signalling in IP and AtT-20 cells, although optimal CRF receptor expression requires the presence of a functional kinase C pathway, thus suggesting cross-talks between both messenger systems.  相似文献   

16.
17.
Generalized gut transit abnormalities are observed in some diabetics with gastroparesis. Relations of gastric emptying abnormalities to colon contractile dysfunction are poorly characterized. We measured colon transit and contractility using wireless motility capsules (WMC) in 41 healthy subjects, 12 diabetics with gastroparesis (defined by gastric retention >5 hours), and 8 diabetics with normal gastric emptying (≤5 hours). Overall numbers of colon contractions >25 mmHg were calculated in all subjects and were correlated with gastric emptying times for diabetics with gastroparesis. Colon transit periods were divided into quartiles by time and contraction numbers were calculated for each quartile to estimate regional colon contractility. Colon transit in diabetics with gastroparesis was prolonged vs. healthy subjects (P<0.0001). Overall numbers of colon contractions in gastroparetics were lower than controls (P = 0.02). Diabetics with normal emptying showed transit and contraction numbers similar to controls. Gastric emptying inversely correlated with overall contraction numbers in gastroparetics (r = -0.49). Numbers of contractions increased from the 1st to 4th colon transit quartile in controls and diabetics with normal emptying (P≤0.04), but not gastroparetics. Numbers of contractions in the 3rd and 4th quartiles were reduced in gastroparetics vs. healthy controls (P≤0.05) and in the 4th quartile vs. diabetics with normal emptying (P = 0.02). Numbers of contractions were greatest in the final 15 minutes of transit, but were reduced in gastroparetics vs. healthy controls and diabetics with normal emptying (P≤0.005). On multivariate analyses, differences in numbers of contractions were not explained by demographic or clinical variables. In conclusion, diabetics with gastroparesis exhibit delayed colon transit associated with reductions in contractions that are prominently blunted in latter transit phases and which correlate with delayed gastric emptying, while diabetics with normal emptying show no significant colonic impairments. These findings emphasize diabetic gastroparesis may be part of a generalized dysmotility syndrome.  相似文献   

18.
Secondary stressors in long-term hypoxic (LTH) fetal sheep lead to altered function of the hypothalamic-pituitary-adrenal axis. Although ACTH is considered the primary mediator of glucocorticoid production in fetal sheep, proopiomelanocortin (POMC) and 22-kDa pro-ACTH (22-kDa ACTH) have been implicated in the regulation of cortisol production in the ovine fetus. This study was designed to determine whether POMC expression and processing are altered after LTH. Pregnant ewes were maintained at high altitude (3,820 m) from day 30 of gestation to near term, when the animals were transported to the laboratory. Reduced Po2 was maintained by nitrogen infusion through a maternal tracheal catheter. On days 139-141, fetal anterior pituitaries were collected from normoxic control and LTH fetuses. We measured POMC and corticotrophin-releasing factor type 1 receptor (CRF1-R) mRNA using quantitative real-time PCR, and we used Western blot analysis for quantitation of ACTH, ACTH precursor, and CRF1-R proteins. We measured plasma ACTH1-39 using a two-site immunoradiometric assay specific for ACTH1-39. Plasma ACTH precursors were measured by ELISA. Anterior pituitary POMC mRNA levels were not different between groups, whereas CRF1-R levels were significantly higher in the LTH anterior pituitaries compared with control (P<0.05). In contrast, protein levels of POMC, CRF1-R, 22-kDa ACTH, and ACTH1-39 were significantly lower in the LTH group. Plasma concentrations of both ACTH precursors and ACTH1-39 were significantly elevated in LTH fetuses, whereas the ratio of plasma precursors to ACTH was significantly lower. We conclude that LTH results in enhanced POMC processing and/or release to ACTH and increased hypothalamic drive.  相似文献   

19.
Proliferation of corticotrophs following adrenalectomy (ADX) was studied by a combination of bromodeoxyuridine (BrdU)-labeling and immunohistochemistry. Rats were adrenalectomized, allowed to survive for 1, 3, 7, and 14 days and given 100 mg/kg body wt BrdU 3 h before sacrifice. BrdU and adrenocorticotropic hormone (ACTH) were detected in the same sections of the anterior pituitary using double-labeling immunohistochemistry. BrdU-labeled cells in the pituitary showed a tendency to increase until 1 week after ADX and slightly decreased at 2 weeks. Corticotrophs were increased to about 1.5 times of the control level 1–2 weeks after ADX. The number of cells double-labeled with both BrdU and ACTH increased markedly after ADX, suggesting active mitosis of existing corticotrophs. On the other hand, the ratios of these double-stained cells to all BrdU-labeled cells and to all corticotrophs were 5–7% and 0.9–1.3%, respectively, even after ADX, suggesting that the majority of corticotrophs which were increased after ADX were recruited from some other type of immature cells. The extent to which the two mechanisms are involved in hyperplasia of corticotrophs after ADX remains to be elucidated.  相似文献   

20.

Background

We investigated whether maternal prenatal emotions are associated with gestational length and birth weight in the large PREDO Study with multiple measurement points of emotions during gestation.

Methods

Altogether 3376 pregnant women self-assessed their positive affect (PA, Positive and Negative Affect Schedule) and depressive (Center for Epidemiologic Studies Depression Scale, CES-D) and anxiety (Spielberger State Anxiety Scale, STAI) symptoms up to 14 times during gestation. Birth characteristics were derived from the National Birth Register and from medical records.

Results

One standard deviation (SD) unit higher PA during the third pregnancy trimester was associated with a 0.05 SD unit longer gestational length, whereas one SD unit higher CES-D and STAI scores during the third trimester were associated with 0.04–0.05 SD unit shorter gestational lengths (P-values ≤ 0.02), corresponding to only 0.1–0.2% of the variation in gestational length. Higher PA during the third trimester was associated with a significantly decreased risk for preterm (< 37 weeks) delivery (for each SD unit higher positive affect, odds ratio was 0.8-fold (P = 0.02). Mothers with preterm delivery showed a decline in PA and an increase in CES-D and STAI during eight weeks prior to delivery. Post-term birth (≥ 42 weeks), birth weight and fetal growth were not associated with maternal prenatal emotions.

Conclusions

This study with 14 measurements of maternal emotions during pregnancy show modest effects of prenatal emotions during the third pregnancy trimester, particularly in the weeks close to delivery, on gestational length. From the clinical perspective, the effects were negligible. No associations were detected between prenatal emotions and birth weight.  相似文献   

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