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List of Publications

Schlundt C, Bucher CH, Tsitsilonis S, Schell H, Duda GN, Schmidt-Bleek K.
Clinical and Research Approaches to Treat Non-union Fracture. Curr Osteoporos.
Rep. 2018 Apr;16(2):155-168. doi: 10.1007/s11914-018-0432-1. Review. PubMed PMID: 29536393.

Seemann R, Graef F, Garbe A, Keller J, Huang F, Duda G, Schmidt-Bleek K, Schaser KD, Tsitsilonis S. Leptin-deficiency eradicates the positive effect of traumatic brain injury on bone healing: histological analyses in a combined trauma mouse model. J Musculoskelet Neuronal Interact. 2018 Mar 1;18(1):32-41.
PubMed PMID: 29504576; PubMed Central PMCID: PMC5881126.

Klatte-Schulz F, Minkwitz S, Schmock A, Bormann N, Kurtoglu A, Tsitsilonis S, Manegold S, Wildemann B. Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics.
Int J Mol Sci. 2018 Jan 30;19(2). pii: E404. doi: 10.3390/ijms19020404. PubMed PMID: 29385715; PubMed Central PMCID: PMC5855626.

Schell H, Duda GN, Peters A, Tsitsilonis S, Johnson KA, Schmidt-Bleek K.
The haematoma and its role in bone healing.
J Exp Orthop. 2017 Dec;4(1):5. doi: 10.1186/s40634-017-0079-3. Epub 2017 Feb 7. Review. PubMed PMID: 28176273; PubMed Central PMCID: PMC5296258.

Minkwitz S, Schmock A, Kurtoglu A, Tsitsilonis S, Manegold S, Wildemann B, Klatte-Schulz F. Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles Tendons after Acute Rupture. Int J Mol Sci. 2017 Oct 20;18(10). pii: E2199. doi: 10.3390/ijms18102199. PubMed PMID: 29053586; PubMed Central PMCID: PMC5666880.

Rose T, Grützkau A, Klotsche J, Enghard P, Flechsig A, Keller J, Riemekasten G, Radbruch A, Burmester GR, Dörner T, Hiepe F, Biesen R.
Are interferon-related biomarkers advantageous for monitoring disease activity in systemic lupus erythematosus? A longitudinal benchmark study.
Rheumatology (Oxford). 2017 Sep 1;56(9):1618-1626. doi: 10.1093/rheumatology/kex220. PubMed PMID: 28859328.

Bartelt A, Jeschke A, Müller B, Gaziano I, Morales M, Yorgan T, Heckt T, Heine M, Gagel RF, Emeson RB, Amling M, Niemeier A, Heeren J, Schinke T, Keller J.
Differential effects of Calca-derived peptides in male mice with diet-induced obesity. PLoS One. 2017 Jun 30;12(6):e0180547. doi: 10.1371/journal.pone.0180547.
eCollection 2017. PubMed PMID: 28666011; PubMed Central PMCID: PMC5493411.

Manegold S, Springer A, Landvoigt K, Tsitsilonis S.
Heterotopic ossification after total ankle replacement: The role of prosthesis alignment.
Foot Ankle Surg. 2017 Jun;23(2):122-127. doi: 10.1016/j.fas.2017.02.008. Epub 2017 Feb 27. PubMed PMID: 28578795.

Graef F, Seemann R, Garbe A, Schmidt-Bleek K, Schaser KD, Keller J, Duda G, Tsitsilonis S.
Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice.
J Musculoskelet Neuronal Interact. 2017 Jun 1;17(2):78-85. PubMed PMID: 28574414; PubMed Central PMCID: PMC5492322.

Wichlas F, Tsitsilonis S, Kopf S, Krapohl BD, Manegold S. Fracture heuristics: surgical decision for approaches to distal radius fractures. A surgeon's perspective.
GMS Interdiscip Plast Reconstr Surg DGPW. 2017 May 22;6:Doc08. doi: 10.3205/iprs000110. eCollection 2017. PubMed PMID: 28580225; PubMed Central PMCID: PMC5442450.

Kaya N, Märdian S, Schwabe P, Manegold S, Tsitsilonis S.
Treatment of Geriatric Proximal Humerus Fractures: Indications and Outcome.
Acta Chir Orthop Traumatol Cech. 2017;84(6):418-423. PubMed PMID: 29351523.

Heckt T, Keller J, Peters S, Streichert T, Chalaris A, Rose-John S, Mell B, Joe B, Amling M, Schinke T. Parathyroid hormone induces expression and proteolytic processing of Rankl in primary murine osteoblasts. Bone. 2016 Nov;92:85-93. doi: 10.1016/j.bone.2016.08.016. Epub 2016 Aug 20. PubMed PMID: 27554428.

Tsitsilonis S, Machó D, Manegold S, Krapohl BD, Wichlas F.
Fracture severity of distal radius fractures treated with locking plating correlates with limitations in ulnar abduction and inferior health-related quality of life.
GMS Interdiscip Plast Reconstr Surg DGPW. 2016 Jul 28;5:Doc20. doi: 10.3205/iprs000099. eCollection 2016. PubMed PMID: 27547692; PubMed Central PMCID: PMC4977376.

Tsitsilonis S, Lindner T, Haas NP, Hahn FM, Marnitz T, Wichlas F. Diagnosing fractures: pain intensity and subjective functional impairment are unreliable markers for initial assessment of possible extremity fractures.
Eur J Emerg Med. 2016 Apr;23(2):155-8. doi: 10.1097/MEJ.0000000000000267. PubMed PMID: 25886777.

Uluçkan Ö, Jimenez M, Karbach S, Jeschke A, Graña O, Keller J, Busse B, Croxford AL, Finzel S, Koenders M, van den Berg W, Schinke T, Amling M, Waisman A, Schett G, Wagner EF.
Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. Sci Transl Med. 2016 Mar 16;8(330):330ra37. doi: 10.1126/scitranslmed.aad8996. Epub 2016 Mar 16. PubMed PMID: 27089206.

Heckt T, Keller J, Reusch R, Hartmann K, Krasemann S, Hermans-Borgmeyer I, Amling M, Schinke T.
No obvious phenotypic abnormalities in mice lacking the Pate4 gene.
Biochem Biophys Res Commun. 2016 Jan 22;469(4):1069-74. doi: 10.1016/j.bbrc.2015.12.104. Epub 2015 Dec 28. PubMed PMID: 26731031.

Märdian S, Giesecke M, Haschke F, Tsitsilonis S, Wildemann B, Schwabe P.
Treatment of Tibial Non-Unions - State of the Art and Future Implications.
Acta Chir Orthop Traumatol Cech. 2016;83(6):367-374. Review. PubMed PMID: 28026731.

Märdian S, Rau D, Schwabe P, Tsitsilonis S, Simon P.
[Operative therapy of fractures of the distal femur. Predictive factors for a complicated course].
Orthopade. 2016 Jan;45(1):32-7. doi: 10.1007/s00132-015-3200-2. Review. German. PubMed PMID: 26614255.

Kuehn SC, Koehne T, Cornils K, Markmann S, Riedel C, Pestka JM, Schweizer M, Baldauf C, Yorgan TA, Krause M, Keller J, Neven M, Breyer S, Stuecker R, Muschol N, Busse B, Braulke T, Fehse B, Amling M, Schinke T.
Impaired bone remodeling and its correction by combination therapy in a mouse model of mucopolysaccharidosis-I. Hum Mol Genet. 2015 Dec 15;24(24):7075-86. doi: 10.1093/hmg/ddv407. Epub 2015 Oct 1. PubMed PMID: 26427607.

Locher RJ, Lünnemann T, Garbe A, Schaser K, Schmidt-Bleek K, Duda G, Tsitsilonis S.
Traumatic brain injury and bone healing: radiographic and biomechanical analyses of bone formation and stability in a combined murine trauma model.
J Musculoskelet Neuronal Interact. 2015 Dec;15(4):309-15. PubMed PMID: 26636276; PubMed Central PMCID: PMC5628590.

Egerer J, Emmerich D, Fischer-Zirnsak B, Chan WL, Meierhofer D, Tuysuz B, Marschner K, Sauer S, Barr FA, Mundlos S, Kornak U.
GORAB Missense Mutations Disrupt RAB6 and ARF5 Binding and Golgi Targeting.
J Invest Dermatol. 2015 Oct;135(10):2368-2376. doi: 10.1038/jid.2015.192. Epub 2015 May 22. PubMed PMID: 26000619.

Tsitsilonis S, Schaser KD, Wichlas F, Haas NP, Manegold S. Functional and radiological outcome of periprosthetic fractures of the ankle.
Bone Joint J. 2015 Jul;97-B(7):950-6. doi: 10.1302/0301-620X.97B7.34871. PubMed PMID: 26130351.

Kleber C, Becker CA, Malysch T, Reinhold JM, Tsitsilonis S, Duda GN, Schmidt-Bleek K, Schaser KD. Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model.
J Orthop Res. 2015 Jul;33(7):965-70. doi: 10.1002/jor.22857. Epub 2015 Mar 31. PubMed PMID: 25732126.

Emmerich D, Zemojtel T, Hecht J, Krawitz P, Spielmann M, Kühnisch J, Kobus K, Osswald M, Heinrich V, Berlien P, Müller U, Mautner VF, Wimmer K, Robinson PN, Vingron M, Tinschert S, Mundlos S, Kolanczyk M. Somatic neurofibromatosis type 1 (NF1) inactivation events in cutaneous neurofibromas of a single NF1 patient.
Eur J Hum Genet. 2015 Jun;23(6):870-3. doi: 10.1038/ejhg.2014.210. Epub 2014 Oct 8. PubMed PMID: 25293717; PubMed Central PMCID: PMC4795057.

Kolanczyk M, Krawitz P, Hecht J, Hupalowska A, Miaczynska M, Marschner K, Schlack C, Emmerich D, Kobus K, Kornak U, Robinson PN, Plecko B, Grangl G, Uhrig, S, Mundlos S, Horn D.
Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome.
Eur J Hum Genet. 2015 May;23(5):720. doi: 10.1038/ejhg.2014.278. PubMed PMID: 25880334; PubMed Central PMCID: PMC4402643.

Kolanczyk M, Krawitz P, Hecht J, Hupalowska A, Miaczynska M, Marschner K, Schlack C, Emmerich D, Kobus K, Kornak U, Robinson PN, Plecko B, Grangl G, Uhrig S, Mundlos S, Horn D.
Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome.
Eur J Hum Genet. 2015 May;23(5):633-8. doi: 10.1038/ejhg.2014.109. Epub 2014 Jun 11. Erratum in: Eur J Hum Genet. 2015 May;23(5):720. PubMed PMID: 24916641; PubMed Central PMCID: PMC4402616.

Tsitsilonis S, Seemann R, Misch M, Wichlas F, Haas NP, Schmidt-Bleek K, Kleber C, Schaser KD.
The effect of traumatic brain injury on bone healing: an experimental study in a novel in vivo animal model. Injury. 2015 Apr;46(4):661-5. doi: 10.1016/j.injury.2015.01.044. Epub 2015 Jan 31. PubMed PMID: 25682315.

Kobus K, Hartl D, Ott CE, Osswald M, Huebner A, von der Hagen M, Emmerich D, Kühnisch J, Morreau H, Hes FJ, Mautner VF, Harder A, Tinschert S, Mundlos S, Kolanczyk M.
Double NF1 inactivation affects adrenocortical function in NF1Prx1 mice and a human patient.
PLoS One. 2015 Mar 16;10(3):e0119030. doi: 10.1371/journal.pone.0119030. eCollection 2015. PubMed PMID: 25775093; PubMed Central PMCID: PMC4361563.

Wichlas F, Tsitsilonis S, Disch AC, Haas NP, Hartmann C, Graef F, Schwabe P.
Long-term functional outcome and quality of life after successful surgical treatment of tibial nonunions.
Int Orthop. 2015 Mar;39(3):521-5. doi: 10.1007/s00264-014-2629-y. Epub 2014 Dec 20. PubMed PMID: 25522800.

Krause M, Keller J, Beil B, van Driel I, Zustin J, Barvencik F, Schinke T, Amling M.
Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy.
Osteoporos Int. 2015 Mar;26(3):987-95. doi: 10.1007/s00198-014-2965-1. Epub 2014 Nov 13. PubMed PMID: 25391248.

Heckt T, Bickert T, Jeschke A, Seitz S, Schulze J, Ito WD, Zimmermann W, Amling M, Schinke T, Horst AK, Keller J.
Increased osteoclastogenesis in mice lacking the carcinoembryonic antigen-related cell adhesion molecule 1.
PLoS One. 2014 Dec 9;9(12):e114360. doi: 10.1371/journal.pone.0114360. eCollection 2014. PubMed PMID: 25490771; PubMed Central PMCID: PMC4260834.

Wichlas F, Haas NP, Disch A, Machó D, Tsitsilonis S.
Complication rates and reduction potential of palmar versus dorsal locking plate osteosynthesis for the treatment of distal radius fractures.
J Orthop Traumatol. 2014 Dec;15(4):259-64. doi: 10.1007/s10195-014-0306-y. Epub 2014 Jul 16. PubMed PMID: 25027735; PubMed Central PMCID: PMC4244564.

Keller J, Catala-Lehnen P, Huebner AK, Jeschke A, Heckt T, Lueth A, Krause M, Koehne T, Albers J, Schulze J, Schilling S, Haberland M, Denninger H, Neven M, Hermans-Borgmeyer I, Streichert T, Breer S, Barvencik F, Levkau B, Rathkolb B, Wolf E, Calzada-Wack J, Neff F, Gailus-Durner V, Fuchs H, de Angelis MH, Klutmann S, Tsourdi E, Hofbauer LC, Kleuser B, Chun J, Schinke T, Amling M.
Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. Nat Commun. 2014 Oct 21;5:5215. doi: 10.1038/ncomms6215. PubMed PMID: 25333900; PubMed Central PMCID: PMC4205484.

Tsitsilonis S, Chatzistergos PE, Mitousoudis AS, Kourkoulis SK, Vlachos IS, Agrogiannis G, Fasseas K, Perrea DN, Zoubos AB.
Anabolic androgenic steroids reverse the beneficial effect of exercise on tendon biomechanics: an experimental study.
Foot Ankle Surg. 2014 Jun;20(2):94-9. doi: 10.1016/j.fas.2013.12.001. Epub 2013 Dec 14. Erratum in: Foot Ankle Surg. 2015 Jun;21(2):148. Panayiotis,Chatzistergos E, Athanasios, Mitousoudis S [corrected to Mitousoudis, Athanasios S]; Stavros, Kourkoulis K [corrected to Kourkoulis, Stavros K]; Ioannis, Vlachos S [corrected to Vlachos, Ioannis S]; George, Agrogiannis [corrected to Agrogiannis, George];Konstantinos, Fasseas [corrected to Fasseas, Konstantinos]; Despina, Perrea N [corrected to Perrea, Despina N]; Aristides, Zoubos B [corrected to Zoubos, Aristides B]. PubMed PMID: 24796826.

Wichlas F, Trzenschik H, Tsitsilonis S, Rohlmann A, Bail HJ.
Biomechanical behavior of MRI-signal-inducing bone cements after vertebroplasty in osteoporotic vertebral bodies: An experimental cadaver study.
Clin Biomech (Bristol, Avon). 2014 May;29(5):571-6. doi: 10.1016/j.clinbiomech.2014.03.002. Epub 2014 Mar 19. PubMed PMID: 24703828.

Kühnisch J, Seto J, Lange C, Schrof S, Stumpp S, Kobus K, Grohmann J, Kossler N, Varga P, Osswald M, Emmerich D, Tinschert S, Thielemann F, Duda G, Seifert W, El Khassawna T, Stevenson DA, Elefteriou F, Kornak U, Raum K, Fratzl P, Mundlos S, Kolanczyk M.
Multiscale, converging defects of macro-porosity, microstructure and matrix mineralization impact long bone fragility in NF1.
PLoS One. 2014 Jan 21;9(1):e86115. doi: 10.1371/journal.pone.0086115. eCollection 2014. PubMed PMID: 24465906; PubMed Central PMCID: PMC3897656.

Schwabe P, Ruppert M, Tsitsilonis S, Melcher I, Schaser KD, Märdian S.
Surgical management and outcome of skeletal metastatic disease of the humerus.
Acta Chir Orthop Traumatol Cech. 2014;81(6):365-70. PubMed PMID: 25651290.

Locher R, Erba PA, Hirsch B, Bombardieri E, Giovannoni L, Neri D, Dürkop H, Menssen HD.
Abundant in vitro expression of the oncofetal ED-B-containing fibronectin translates into selective pharmacodelivery of (131)I-L19SIP in a prostate cancer patient.
J Cancer Res Clin Oncol. 2014 Jan;140(1):35-43. doi: 10.1007/s00432-013-1538-6. Epub 2013 Oct 17. PubMed PMID: 24132461.

Keller J, Schinke T.
The role of the gastrointestinal tract in calcium homeostasis and bone remodeling. Osteoporos Int. 2013 Nov;24(11):2737-48. doi: 10.1007/s00198-013-2335-4. Epub 2013 Mar 28. Review. PubMed PMID: 23536255.

Wichlas F, Haas NP, Lindner T, Tsitsilonis S.
Closed reduction of distal radius fractures: does instability mean irreducibility?
Arch Orthop Trauma Surg. 2013 Aug;133(8):1073-8. doi: 10.1007/s00402-013-1758-x. Epub 2013 May 5. PubMed PMID: 23644896.

Alten R, Maleitzke T.
Tocilizumab: a novel humanized anti-interleukin 6 (IL-6) receptor antibody for the treatment of patients with non-RA systemic, inflammatory rheumatic diseases.
Ann Med. 2013 Jun;45(4):357-63. doi: 10.3109/07853890.2013.771986. Epub 2013 May 8. Review. PubMed PMID: 23650978.

Hannemann A, Breer S, Wallaschofski H, Nauck M, Baumeister SE, Barvencik F, Amling M, Schinke T, Haring R, Keller J.
Osteocalcin is associated with testosterone in the general population and selected patients with bone disorders.
Andrology. 2013 May;1(3):469-74. doi: 10.1111/j.2047-2927.2012.00044.x. Epub 2013 Jan 13. PubMed PMID: 23315980.

Manegold S, Haas NP, Tsitsilonis S, Springer A, Märdian S, Schaser KD.
Periprosthetic fractures in total ankle replacement: classification system and treatment algorithm.
J Bone Joint Surg Am. 2013 May 1;95(9):815-20, S1-3. doi: 10.2106/JBJS.L.00572. PubMed PMID: 23636188.

Albers J, Keller J, Baranowsky A, Beil FT, Catala-Lehnen P, Schulze J, Amling M, Schinke T.
Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin.
J Cell Biol. 2013 Feb 18;200(4):537-49. doi: 10.1083/jcb.201207142. Epub 2013 Feb 11. PubMed PMID: 23401003; PubMed Central PMCID: PMC3575535.

Tsitsilonis S, Schaser KD, Kiefer H, Wichlas F.
The treatment of the proximal humeral fracture with the use of the PHN Nailing System: the importance of reduction.
Acta Chir Orthop Traumatol Cech. 2013;80(4):250-5. PubMed PMID: 24119472.

Pasold J, Engelmann R, Keller J, Joost S, Marshall RP, Frerich B, Müller-Hilke B.
High bone mass in the STR/ort mouse results from increased bone formation and impaired bone resorption and is associated with extramedullary hematopoiesis.
J Bone Miner Metab. 2013 Jan;31(1):71-81. doi: 10.1007/s00774-012-0394-9. Epub 2012 Nov 29. PubMed PMID: 23192248.

Tsitsilonis S, Druschel C, Wichlas F, Haas NP, Schwabe P, Bail HJ, Schaser KD.
Necrotizing fasciitis: is the bacterial spectrum changing?
Langenbecks Arch Surg. 2013 Jan;398(1):153-9. doi: 10.1007/s00423-012-0983-z. Epub 2012 Jul 26. PubMed PMID: 22833058.

Schaser KD, Melcher I, Druschel C, Tsitsilonis S, Disch AC.
[Surgical management of thoracolumbar spinal sarcoma].
Orthopade. 2012 Aug;41(8):659-73. doi: 10.1007/s00132-012-1911-1. German. PubMed PMID: 22825054.

Bail HJ, Sattig C, Tsitsilonis S, Papanikolaou I, Teichgräber UK, Wichlas F.
Signal-inducing bone cements for MRI-guided spinal cementoplasty: evaluation of contrast-agent-based polymethylmethacrylate cements.
Skeletal Radiol. 2012 Jun;41(6):651-7. doi: 10.1007/s00256-011-1264-6. Epub 2011 Sep 9. PubMed PMID: 21904991.

Keller J, Catala-Lehnen P, Wintges K, Schulze J, Bickert T, Ito W, Horst AK, Amling M, Schinke T.
Transgenic over-expression of interleukin-33 in osteoblasts results in decreased osteoclastogenesis.
Biochem Biophys Res Commun. 2012 Jan 6;417(1):217-22. doi: 10.1016/j.bbrc.2011.11.088. Epub 2011 Nov 27. PubMed PMID: 22142849.

Seitz S, Keller J, Schilling AF, Jeschke A, Marshall RP, Stride BD, Wintermantel T, Beil FT, Amling M, Schütz G, Tuckermann J, Schinke T.
Pharmacological estrogen administration causes a FSH-independent osteo-anabolic effect requiring ER alpha in osteoblasts.
PLoS One. 2012;7(11):e50301. doi: 10.1371/journal.pone.0050301. Epub 2012 Nov 27. PubMed PMID: 23209701; PubMed Central PMCID: PMC3507728.

Keller J, Brink S, Busse B, Schilling AF, Schinke T, Amling M, Lange T. Divergent resorbability and effects on osteoclast formation of commonly used bone substitutes in a human in vitro-assay.
PLoS One. 2012;7(10):e46757. doi: 10.1371/journal.pone.0046757. Epub 2012 Oct 10.
PubMed PMID: 23071629; PubMed Central PMCID: PMC3468634.

Schulze J, Bickert T, Beil FT, Zaiss MM, Albers J, Wintges K, Streichert T, Klaetschke K, Keller J, Hissnauer TN, Spiro AS, Gessner A, Schett G, Amling M, McKenzie AN, Horst AK, Schinke T.
Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells.
Bone Miner Res. 2011 Apr;26(4):704-17. doi: 10.1002/jbmr.269. PubMed PMID: 20939024.

Albers J, Schulze J, Beil FT, Gebauer M, Baranowsky A, Keller J, Marshall RP, Wintges K, Friedrich FW, Priemel M, Schilling AF, Rueger JM, Cornils K, Fehse B, Streichert T, Sauter G, Jakob F, Insogna KL, Pober B, Knobeloch KP, Francke U, Amling M, Schinke T.
Control of bone formation by the serpentine receptor Frizzled-9.
J Cell Biol. 2011 Mar 21;192(6):1057-72. doi: 10.1083/jcb.201008012. Epub 2011 Mar 14. PubMed PMID: 21402791; PubMed Central PMCID: PMC3063134.

Schulze J, Albers J, Baranowsky A, Keller J, Spiro A, Streichert T, Zustin J, Amling M, Schinke T. Osteolytic prostate cancer cells induce the expression of specific cytokines in bone-forming osteoblasts through a Stat3/5-dependent mechanism. Bone. 2010 Feb;46(2):524-33. doi: 10.1016/j.bone.2009.09.024. Epub 2009 Sep 29. PubMed PMID: 19796718.

Huebner AK, Keller J, Catala-Lehnen P, Perkovic S, Streichert T, Emeson RB, Amling M, Schinke T. The role of calcitonin and alpha-calcitonin gene-related peptide in bone formation. Arch Biochem Biophys. 2008 May 15;473(2):210-7. doi: 10.1016/ Epub 2008 Feb 16. Review. PubMed PMID: 18307972.