271 research outputs found
Reconciling the interests of the economic diversification participants in a single-industry town
Π Π°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡΡΡ ΠΏΡΠΎΠ±Π»Π΅ΠΌΡ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² ΡΡΠ°ΡΡΠ½ΠΈΠΊΠΎΠ² ΠΏΡΠΎΡΠ΅ΡΡΠ° Π΄ΠΈΠ²Π΅ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΠΊΠΈ ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π° Π² ΠΏΡΠΎΡΠ΅ΡΡΠ΅ ΡΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ΠΌ ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π° Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠΈ Π΄ΠΈΠ²Π΅ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ. Π¦Π΅Π»ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠΎΠ² Π³Π°ΡΠΌΠΎΠ½ΠΈΠ·Π°ΡΠΈΠΈ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² ΡΡΠ°ΡΡΠ½ΠΈΠΊΠΎΠ² ΠΏΡΠΎΡΠ΅ΡΡΠ° Π΄ΠΈΠ²Π΅ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΠΊΠΈ ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π° Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΏΠΎΠ»Π½ΠΎΠ³ΠΎ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² ΠΈ ΡΠΎΠΏΠΎΡΡΠ°Π²Π»Π΅Π½ΠΈΡ Π΅Π΅ Ρ ΠΌΠΎΠ΄Π΅Π»ΡΡ ΠΎΡΠ΄Π΅Π»ΡΠ½ΠΎ Π²Π·ΡΡΠΎΠ³ΠΎ ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π°. ΠΠ΅ΡΠΎΠ΄Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: ΡΠΈΡΡΠ΅ΠΌΠ½ΡΠΉ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄, Π°Π½Π°Π»ΠΈΠ· ΠΈ ΡΠΈΠ½ΡΠ΅Π·, ΠΏΠΎΡΡΡΠΎΠ΅Π½ΠΈΠ΅ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ² ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ Π΄ΠΈΠ°Π³ΡΠ°ΠΌΠΌΡ ΠΠΉΠ»Π΅ΡΠ°-ΠΠ΅Π½Π½Π°, ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΎΡΠΈΠΊΠΈ, ΠΏΠΎΡΡΡΠΎΠ΅Π½ΠΈΠ΅ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΈ ΡΡΠ΄ΠΎΠ² Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ, Π³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΌΠ΅ΡΠΎΠ΄ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΡ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ² ΠΈ ΠΏΠΎΡΡΡΠΎΠ΅Π½ΠΈΡ ΠΈΠ΅ΡΠ°ΡΡ
ΠΈΠΈ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ². Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π° ΠΌΠΎΠ΄Π΅Π»Ρ ΠΏΠΎΠ»Π½ΠΎΠ³ΠΎ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π³ΡΡΠΏΠΏ Π»ΠΈΡ, Π² ΠΊΠΎΡΠΎΡΠΎΠΉ ΠΎΡΡΠ°ΠΆΠ΅Π½Ρ ΡΡΠ΅ΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΏΠ΅ΡΠ΅ΡΠ΅ΡΠ΅Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ², Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΠ΅ΡΠ°ΡΡ
ΠΈΡ ΡΠΈΡΠ»Π° ΡΠΎΠ³Π»Π°ΡΡΠ΅ΠΌΡΡ
ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ². ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ Π³ΡΡΠΏΠΏΡ ΡΡΠ°ΡΡΠ½ΠΈΠΊΠΎΠ² ΠΏΡΠΎΡΠ΅ΡΡΠ° Π΄ΠΈΠ²Π΅ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π°, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠ°Π·Π³ΡΠ°Π½ΠΈΡΠ΅Π½ΠΎ ΠΏΠΎΠ½ΡΡΠΈΠ΅ ΡΡΠ°ΡΡΠ½ΠΈΠΊΠ° ΠΈ ΡΠΎΠ»ΠΈ (ΡΡΠ½ΠΊΡΠΈΠΈ) ΡΡΠ°ΡΡΠ½ΠΈΠΊΠ° Π² Π΄Π°Π½Π½ΠΎΠΌ ΠΏΡΠΎΡΠ΅ΡΡΠ΅. ΠΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΎ ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΎ ΡΠΈΡΠ»ΠΎ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ² Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΡΠΈΡΠ»Π° ΡΡΠ°ΡΡΠ½ΠΈΠΊΠΎΠ², ΡΡΠΈ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΡ ΠΎΠ΄Π½ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎ ΡΠΎΠ³Π»Π°ΡΡΡΡΡΡ, Π½Π° ΠΏΡΠΈΠΌΠ΅ΡΠ΅ ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π° ΠΠ°Π»ΡΠ°Π½ ΠΠ΅ΠΌΠ΅ΡΠΎΠ²ΡΠΊΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½ΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΏΠΎΡΡΡΠΎΠ΅Π½Π° ΠΌΠΎΠ΄Π΅Π»Ρ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² Π½Π° ΠΏΡΠΈΠΌΠ΅ΡΠ΅ ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π° ΠΠ°Π»ΡΠ°Π½Π°. ΠΠΎΠ»ΡΡΠ΅Π½Π½Π°Ρ ΠΌΠΎΠ΄Π΅Π»Ρ ΠΈΠΌΠ΅Π΅Ρ ΡΡΠ°ΠΏΠ΅ΡΠΈΠ΅Π²ΠΈΠ΄Π½ΡΡ ΡΠΎΡΠΌΡ, ΡΡΠΎ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΠ΅Ρ ΠΎ Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎ Π½Π΅Π±ΠΎΠ»ΡΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΎΠ±ΡΠΈΡ
ΡΠΎΠ³Π»Π°ΡΡΠ΅ΠΌΡΡ
ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ². ΠΠ²ΡΠΎΡ ΠΏΡΠΈΡ
ΠΎΠ΄ΠΈΡ ΠΊ Π²ΡΠ²ΠΎΠ΄Ρ, ΡΡΠΎ Π² ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π΅ ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ ΡΡΠ΅ΡΠ³ΠΎΠ»ΡΠ½ΠΈΠΊ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² Β«Π°Π΄ΠΌΠΈΠ½ΠΈΡΡΡΠ°ΡΠΈΡ Π³ΠΎΡΠΎΠ΄Π° - ΠΌΠ°Π»ΡΠΉ Π±ΠΈΠ·Π½Π΅Ρ Π² ΡΠΎΠ»ΠΈ ΠΈΠ½Π²Π΅ΡΡΠΎΡΠ° - Π²ΡΠ·Β», ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΡΡΠΈΠΉ ΠΎΡΠ½ΠΎΠ²Ρ Π² ΠΈΠ΅ΡΠ°ΡΡ
ΠΈΠΈ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π° ΠΠ°Π»ΡΠ°Π½. Π¦Π΅Π½ΡΡΠ°Π»ΡΠ½ΠΎΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ ΠΏΡΠΈ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² Ρ ΠΏΡΠΎΡΠΈΠΌΠΈ ΡΡΠ°ΡΡΠ½ΠΈΠΊΠ°ΠΌΠΈ Π·Π°Π½ΠΈΠΌΠ°Π΅Ρ ΠΈΡΠΊΠ»ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π°Π΄ΠΌΠΈΠ½ΠΈΡΡΡΠ°ΡΠΈΡ Π³ΠΎΡΠΎΠ΄Π°. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π΅ Π΄Π°Π½Π½ΡΡ
Π²ΡΠ²ΠΎΠ΄ΠΎΠ² Π²Π½Π΅ΡΠ΅Π½Ρ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ΠΈΡ ΠΏΠΎ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡΠΌ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅Π³ΠΎ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠΎΠ² Π½Π° ΠΏΡΠΈΠΌΠ΅ΡΠ΅ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°Π΅ΠΌΠΎΠ³ΠΎ ΠΌΠΎΠ½ΠΎΠ³ΠΎΡΠΎΠ΄Π°.The article explores the problems of reconciling the interests of single-industry towns, a need that arises from the entire process of industry development management through a diversification strategy. The aim of this study is to develop tools to harmonize the interests of the single-industry towns, based on a model of full harmonization with the model of an individual single-industry town. Methods of the research: system approach, analysis and synthesis, building a set of harmonized interests with the application of the Eulerian-Venn diagram, combinatorics methods, construction of economic indicators and series of dynamics, graphical method of presentation of results and building the hierarchy of interests. Results of the study. The paper introduces the model for fully reconciling the interests of different groups of persons, reflecting the areas of possible intersecting interests and the hierarchy of the number of interests involved. The article proposes the main groups of participants in the diversification process and the differentially concept of participant and the role (function) of the participant in the diversification process. The author justifies and estimates the number of sets depending on the number of participants whose interests are concurrently reconciled in Kaltan case study. The proposed model is used for Kaltan, Kemerovo region case study. The result ing model is of a trapezoidal form, which indicates that there are quite a few common consenting interests. The author concludes that a triangle of interests Β«city administration - small business as investor - universityΒ» is formed. This triangle represents the highest level of harmonization of interests in the hierarchy. The city administration is in central position in reconciling interests with other participants. By the example of the considered single-industry town and based on these findings the suggestion on further harmonization of interests was made
Correct evaluation of Social Policy
The problem surrounding Social Policy in Russia is due to internal and external factors. The aauthors analyse the challenges of effective social policy evaluation with different analytical materials by first given the definition of effectiveness with the aid of formula, then describe the types of social policy presented by Esping-Andersen and Abrahamson. The authors also analyze three main factors (inflation rate of oil, the rate of dollars against rubles and the pulling out of foreign investors) that lead to crises in Russia. In conclusion, the authors decide that the insufficient effectiveness of Russia's social policy is primarily associated with tight budget constraints due to the crisis
Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)2D3 response to short-term treatment with 1,25-dihydroxyvitamin D3in vivo
Background
Although much is known about the regulation of osteoclast (OC) formation and activity, little is known about OC senescence. In particular, the fate of of OC seen after 1,25-(OH)2D3 administration in vivo is unclear. There is evidence that the normal fate of OC is to undergo apoptosis (programmed cell death). We have investigated the effect of short-term application of high dose 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on OC apoptosis in an experimental rat model.
Methods
OC recruitment, augmentation and apoptosis was visualised and quantitated by staining histochemically for tartrate resistant acid phosphatase (TRAP), double staining for TRAP/ED1 or TRAP/DAPI, in situ DNA fragmentation end labelling and histomorphometric analysis.
Results
Short-term treatment with high-dose 1,25-(OH)2D3 increased the recruitment of OC precursors in the bone marrow resulting in a short-lived increase in OC numbers. This was rapidly followed by an increase in the number of apoptotic OC and their subsequent removal. The response of OC to 1,25-(OH)2D3 treatment was dose and site dependent; higher doses producing stronger, more rapid responses and the response in the tibiae being consistently stronger and more rapid than in the vertebrae.
Conclusions
This study demonstrates that (1) after recruitment, OC are removed from the resorption site by apoptosis (2) the combined use of TRAP and ED1 can be used to identify OC and their precursors in vivo (3) double staining for TRAP and DAPI or in situ DNA fragmentation end labelling can be used to identify apoptotic OC in vivo
Adult Patients with Congenital Adrenal Hyperplasia Have Elevated Blood Pressure but Otherwise a Normal Cardiovascular Risk Profile
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96615.pdf (publisher's version ) (Open Access)OBJECTIVE: Treatment with glucocorticoids and mineralocorticoids has changed congenital adrenal hyperplasia (CAH) from a fatal to a chronic lifelong disease. Long-term treatment, in particular the chronic (over-)treatment with glucocorticoids, may have an adverse effect on the cardiovascular risk profile in adult CAH patients. The objective of this study was to evaluate the cardiovascular risk profile of adult CAH patients. DESIGN: Case-control study. PATIENTS AND MEASUREMENTS: In this case-control study the cardiovascular risk profile of 27 adult CAH patients and 27 controls, matched for age, sex and body mass index was evaluated by measuring ambulatory 24-hour blood pressure, insulin sensitivity (HOMA-IR), lipid profiles, albuminuria and circulating cardiovascular risk markers (PAI-1, tPA, uPA, tPA/PAI-1 complex, hsCRP, adiponectin, IL-6, IL-18 and leptin). RESULTS: 24-Hour systolic (126.3 mmHg+/-15.5 vs 124.8 mmHg+/-15.1 in controls, P = 0.019) and diastolic (76.4 mmHg+/-12.7 vs 73.5 mmHg+/-12.4 in controls, P<0.001) blood pressure was significantly elevated in CAH patients compared to the control population. CAH patients had higher HDL cholesterol levels (P<0.01), lower hsCRP levels (P = 0.03) and there was a trend toward elevated adiponectin levels compared to controls. Other cardiovascular risk factors were similar in both groups. CONCLUSION: Adult CAH patients have higher ambulatory blood pressure compared to healthy matched controls. Other cardiovascular risk markers did not differ, while HDL-cholesterol, hsCRP and adiponectin levels tended to be more favorable
Modified-release hydrocortisone to provide circadian cortisol profiles
Context: Cortisol has a distinct circadian rhythm regulated by the brain's central pacemaker. Loss of this rhythm is associated with metabolic abnormalities, fatigue, and poor quality of life. Conventional glucocorticoid replacement cannot replicate this rhythm.
Objectives: Our objectives were to define key variables of physiological cortisol rhythm, and by pharmacokinetic modeling test whether modified-release hydrocortisone (MR-HC) can provide circadian cortisol profiles.
Setting: The study was performed at a Clinical Research Facility.
Design and Methods: Using data from a cross-sectional study in healthy reference subjects (n = 33), we defined parameters for the cortisol rhythm. We then tested MR-HC against immediate-release hydrocortisone in healthy volunteers (n = 28) in an open-label, randomized, single-dose, cross-over study. We compared profiles with physiological cortisol levels, and modeled an optimal treatment regimen.
Results: The key variables in the physiological cortisol profile included: peak 15.5 mu g/dl (95% reference range 11.7-20.6), acrophase 0832 h(95% confidence interval 0759-0905), nadir less than 2 mu g/dl (95% reference range 1.5-2.5), time of nadir 0018 h (95% confidence interval 2339-0058), and quiescent phase (below the mesor) 1943-0531 h. MR-HC 15 mg demonstrated delayed and sustained release with a mean (SEM) maximum observed concentration of 16.6 (1.4) mu g/dl at 7.41 (0.57) h after drug. Bioavailability of MR-HC 5, 10, and 15 mg was 100, 79, and 86% that of immediate-release hydrocortisone. Modeling suggested that MR-HC 15-20 mg at 2300 h and 10 mg at 0700 h could reproduce physiological cortisol levels.
Conclusion: By defining circadian rhythms and using modern formulation technology, it is possible to allow a more physiological circadian replacement of cortisol. (J Clin Endocrinol Metab 94: 1548-1554, 2009
Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies
Context: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction.
Objective: Assess tildacerfont safety and efficacy.
Design and setting: Two Phase 2 open-label studies.
Patients: Adults with 21OHD.
Intervention: Oral tildacerfont 200 to 1000 mg once daily (QD) (n = 10) or 100 to 200 mg twice daily (n = 9 and 7) for 2 weeks (Study 1), and 400 mg QD (n = 11) for 12 weeks (Study 2).
Main outcome measure: Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4 β€ 2Γ upper limit of normal (ULN) or A4 > 2Γ ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments.
Results: In Study 1, evaluable participants with baseline A4 > 2Γ ULN (n = 11; 19-67 years, 55% female) had reductions from baseline in ACTH (-59.4% to -28.4%), 17-OHP (-38.3% to 0.3%), and A4 (-24.2% to -18.1%), with no clear dose response. In Study 2, participants with baseline A4 > 2Γ ULN (n = 5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 β€ 2Γ ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%).
Conclusions: For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal
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