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NuW1PK+8m59helU5NnqEn01A21fpawbcsRiQx1qyl8h1CXlpSW5OFMJpwGSNpcKEOKD4RSqh142T0W6Q0QuT8ppSsXsN9rG7H4a0xlJYBe0guFcC7btRcA0ouDbnkuUXM6FtXorCTPUGYrcFsn0rL161BmW1UTzkjM3qR0UsL7IWWjpQaq0WaydIrROkVgtSG0GppVpbKtk5lXY6tTqtjtp40LadLqfa5qVqYw+XSaOuNSDjulCSBYpsHYnytNMKWho4WCft/YjOpRvp3I/27v1IOaR8TTn0UfpUSblx5u50eGMw4LCZ7G0TaUS+YYndbLfvvjCyIRi02KjZEptIgwvrATnU2zmbxqKt1eh5fv4k4ybl/QdfVR6iF27ZsedmgfuY3nrkjcs1U/g5n/kVOOO4Pym71gieh6hJw/G0OcBruNH7OJEu03EBHzVio63ByUHrw7T2wtxKf3x5JiB4jY019SanaDfmBukVm58/9XV/XKvhDpb3DtHtb7463NJ66wOqfzE2tzPIcnIFeYjISxNyS0qeXUK+AxA5HRyNlGwvFafbcfqme2H6GoAX16pzjJ4bOmpg8WV3Ug6Btk4WAyF8NNAF3LgO5lcHHscwb5q5AmctIOaNmhrvhFhv/+LB1WyuZ8NcF0lsJqjgAm+Cc128C+3udPEItfiDockrL2Pm1Cbi5KCZpK6ANhjgM6qkeqhfDIp+hwrrUWrBzIJ51cP9LDtNZf0BLd9DXWBPNS6cVZBgW6TTBd/k1AJrSDeUvB6fu9lrnW07cp8q2uCknGaqDyCtotFcfDcfNIdsHlHUx+ceumjgwK3lR278/YzcG9LiObbBULfHo9PR8qElt01z3L3ruh85HdKuG16i79Lf38hPyfm7wx4qaKehRlD9H/zqUfiVJufdT23g3LVNYqO93mFMz5x815GtRzr2Xnbqm0vWU9pQN7lhYmBigyds0V8hdD7ya0H4/TcPjAjCL4mKycCAap8Br94CunkWQ9owB3wCcEwVaasT5IEJ8pYYUtYBtinUmYDCHrEghhCWhepF6yGLua09rqIyu3MyBQAZp6A6bKA3gMLpbA9NJREjw3mcA2Wo0WX8XmrhAKVdsZBbvJauGRhYZ6NzlKcBls2usQ9OnTTXT2fn1t2+KNSbSvh9jhrlCIU/rTj7sstm969aferb/L+P+rkJnY3JmZNWzyj/J9e15bsbsjW2xsZgk3iX+23lPeU/Lz6LT5sAe2bJDUwDARL2x0DtdDBn0Oc7IcqdKdkG/pdFdsP4u9j4wQO2MCfYy/wG2a9yawwcEkuhTVVDOSCL18NMgOwXC/UuIE7AKmdyckwsdHQiiXxwu9CSUV3h8SYC0PbnkosRixkOoNWYyUCbQMnCaXT6ALegd/oiC9WBF/x1qtdbZqR2U/3B25MLuwIW5ePxRmSfcO2kCy+c1D1v/qdH+IbR9+jRdltL17CyjL74vafr2yINW4AZngRAtQCw1DTyXVJ0In4yJ+QJJaSQFgjSywiSKckZS6EJRg52MmAptDOXuTAdDp3uH/bUfDSHOGJGk9wAVBwp2OkncmRk2GqP2GJFePft8e0JakFMc+SQ1d7gjsTxj447l/NuWmjKgCC7clNQkANiUevswLN2a8E8AanZMQF9NNLco0o2mCoEyk6rw84J4L9EOVDQ0UjWpmIKJ3MGtKi+rSzqYOIcdhBeHaLlaIR7su/eYzT2lEwTL+94QvnZi5d/LzDbErj4Xp3n0Za71g4sC08xua67YucPLlc++PiOD7+xbMCq01kMuqDzxi8Jf7rqN688fOl1Lymf3vk35eqTF+eV3+Z2fbXz4C5OXnjNHUc3LErd81zu8q98n058+gQ1XX7wzWu/usbhrp/SUm8xpKgaXhvDsINkNymakO4AO2Yn5C60kcwmLmWkD5fksKWQAkrPLclzLYWZcDa5JE9W3V/wPZYBI85NAW1iiYHFqC9nikdMGltz1zTLArycbC04pyIBnSb0QhYDTWeDF2IwEps7PCE1eeqCz3geiGSDgWhnFoCpSj4mu+BrOV3OTmDSbGckClRmWAHJDNTPomEErgVVC/ABpsJ1tuOh+gZfvXuOZ1bT3gWPlvdc8tjf9971f75zfW5ondUjcBZeozFd0CeNbH3p5IJ9lyy63FYz0ds3fdF2i96w1VavBbT61Fl+hnIJvP7z0dYd66g703+ETv3ZtuPfvGzeTY8NL9/zWqveZDPkDTanOP/61cVbF7751Nf+fu/OBfGHr27tXXr/1thCm00JD6zecy0dZX70AW6VbpXmAChGM2khTBeyOIlJDRZRNUJjKRiA4nXV4JDV4vR1WiI+oXI88Fe67K9/VR7n7qycCN9VHv9r5ZwdK7iY6G4EF8ZPMgRjnPUl2ZqQTSwOh9E28D7ADZa1GFsrEo0FZcBkHa5r8vhUxncBdzdSaypJic0aDvFwCUyNxi3CowxopcXX2Vcu/MrGb5TpJrq61qL8Sbnjlhn52yz6LVu7Znfb0xOPLZdv1Fy+cbFysvwX5ST93/QnlKcr9LXKgOf+lbJMzRfSWTRh09+/lTD6VGOKZvDjrYRimJMgWsNgKzlXuYUNVDq5XyAYjxqFd45FfdD1xhYF35vRSUd60F8RSdsCejoAnpxsSMC3UjmYkJtOYLTSmSyEkCQWjH/VoZlJiXZmgsGsd2ZFGHUUeVFEoBpEiAYg7Vc/dbtvufTiGzatWHbtl2+f290mivQJZfC02N4xe84G4dHyHdf1Ttvma3bau6h7WaihPf4AfZk20BfuWH7xlHzwLNsRJDEymdzMbAdYCW9CjpbkhoQcSMkJFp4SSrJgAaGlcneFKAhhfcAoquCCp4ADabRgpExOMddzCkhs2AcjCuTkCeKw19PGvMpGjM2QQkMUZLnRF27BtoRYCE04nwEB9z7FAjZ+EEEwcOBP+UMVTgyrxgWckEiMgkieZUWk/oyGZPqVjyzKcWWZctyifERZFPGk8hzX3J+RMv3s7SxDMoSNPOntwXhd2/Ge3mbluZP4oerT/RlQZ4AtKGALhdiJCzzzZqBeFOgXB9+cyglGHowfWjAYL3sZ9GuB9zFz0gF0aXDA6J31Tcjsckg8pNUgnnOhHRgOhFvbEP6xSFyWdiZdFOmho8gGNDKVRm1UDPOusMi7snAe1YiarIG6MpR4uB+LLSL3Y4+n3CvarbZyr+eWb387w2mUd957j3oPvv/BB72c5j3lHep9r/wpvffbvJO+1lxPX6upUdrrm5V2n1Npq6mhx50PbdqkPK48TtPP0q4HnqWp8rMPPfRQOUCXPfgs1/TsA3RZ+dlNvzmLhzJkKXmGPMZ4yF6SexLy90rynETV9fnRONcHsYUaWLoHzq4pydeoxAKm+TGGmNqAaZbm5HvEQ88sX9d7AOlyjbVYJ1yNWqJBzNtqNXZvoCPZ3TNn3qVbbv/6Y/9aHGaAuccOtjUyaTIC5jnguD5N9RZv97zvY7xTswjudSRTuc/xjIRUMoSgOM5FUfJAxwjRSCgasWY7Q1lA1wLHJFLIwjSgYz+V70RD4oqwpwSdltPg/U40G3E0wFoA1U5mR1B44RJvZ+PgUEbQvOCVDo033AS74vJyzGTjBWWP4ldgMIFMwbhXJMSU3nl8rp436bVv/Ynetnby0n0vbd8hRztnb9usPH3wceWDvjl1S5fR9iLn/6Vy8Gf3iY994Vrq2zV31r3lr93Dm+hl1PrQN6n3slDgSuU3+7+hvH7VVWuoqH/gqk3/PnmKs3/mmxcusTtSyZUrF0TSejGVXjwwOVerjTW3JOKz6jiTweGcMbfPFo9Y+2KxFf45Wm5wd+8FV3jqw+9s3taVjQQ/uOlL3+e1Swfv2HbtwIqfUIdxw+K1yl+v2jHlc1y6t5Tb3vz7y7fdvPPYQ0P2jueuu0956tpdWzyNv93/EL3q6w/+L6/W8rZy74dfOz27z5xzfE2598R+GMU26c5duegX79Xqdm7eoPz6+mue9/oHLl7xzpx59u6eSy9bvLjeNdHVN2FZ3yyNtjs7EJ5qcWhoV4z3zvF4/UIsMHdRNKs3NDRfcMW0DQmr5ao752xYF4tt33nddXe6bG/cvnf79tZgU4A6fsJteLZnnn1yz/oNpOoj6gnw/nxyJbmR3EFvIrImIa8tyVJCvjUl31SSdyeL0k3o8kl7DLHiTRKe3vQlcBRvssjXIyoHxBlNyJtSciuIyJ0JOXFCXl8avnB9Qh+TSQkDHxeW5PWWQp6l+2SXRc6W5GwCTgo7oMlXGr7ct0PNcfkshT3QdHNSvr0k35Is3r4Hf+32W+GH99yOp3skcDvvUrGsYevIsIplZ1nkmSOFQe4TednID4UdIy1qc59FnjFSWMp/Ii8fKcyaqYeG4Zl9M2yxQt8MPXxouG/WTFtMHrQMLx1cBq2Dy/TyUsvwsqXLbTFyZMbMvlmDS5ctj1f+6DktDArn14NIZjSbUKxdYnHl2utRcH07QDeK7ihahsKeGtAFE0C0pbXQSgDRoTa4SSw6XUzKo9dDszuxfoeKGuxeQGs94P/GhQSNc2mQPowqxwX0dH0gYBhKBqNqN6G3zLlMvM7EZ9M9fLYHmsEHdoDdAQ+44tMBGNSZABXGeZphTrQDHWopf90LX9j5i39Zl6zzeTpD/iU2m6ve5gq3dfvqLc3eeL39nvuURuXjb8ye55u+8ouzbV16quUESo2NJtuUOXfuSiVnt1hfDcSmheqDA7Paa4O2VM+0UHPt0986+rurU00r4l2XX5B0TbampzRNWjO9w8EfZYAKnGP6y95rLu1KDm6VprfMmNKebfb0mm2xjoTT6Yn09ixPxuZPhQvLkpvyBxd3bbikr1XDiYJZZ6ox69xtcVuDoHPGfJ7++X2WxMKOVrOhRtTxfCiebU2mvFvvOiAc2pQPtuZWbt+R3jrZ5rHmLtq6qXzqjF+uYvovg87vAr6/CP3qvgTLrq5A9V5IA3cBgzYni+ksslw6AbyetSAUAJtQWAnKPU1hzi9cMohznhULgb4cWjorThTv5ZupVwMk16CWFE1qyB/OvBygIL/YAfoT9GtcGw12MBBkovgRXZy/qaZv+syDBwuP3L9rpbuhtuWqi6/ItsQ2br5285VLp4lWytWIvpap4fSmxTNsVv8F07sstGvaK7vWu7jg1EUrVg7k7bbeX+/NtTQ28GJjvcFwUueaNEH45iM/XTl/22QfZ2pqMBo0tllLvvLo725YfvtA1qapq9NplT/ytYFAe7SlzsY1eGvraH0gZgq188Xyu3W+lfO/PffmFXPa/WY95Sw3JKe1r1owb1JbTe1LBt/6TYg37wI6bgc6+sm14JUi3mopFRtakHANDiDchoR8eUlekmApwSXVlCCVr0vI3hPyCnBRS8WAl0WU1oGUewN46iXwyRWWQpyB+GK8jmUNe0D0rwfqB7wgTr5cIb4CjKPgaGjRz9uJAlUnymYQspYGuA1Sd/kGkCpzPMDuLRGH67ykE0/1iNiZV0oxnl1xTHVOHXOPoiA6oQh4SFlw/NH4MfSKmZ3I+H9wH6PhzuoTldvBAE6pw67ewH/wzRXkW71/15dO7r7rmhn9T9Kud3bbUvRLJ2/ZtfHCuU8qP3tntzid3tmZXnrNkX1bN3dPDgSnTFoyb9PyxqDfLwKoXLm6LebzOhoSmUCgoX5SbtHg5js2bsjlsumVl37x4ik5v79n2vr57QlXo9PR5IulgyHNfbtPfqm/dvc7ys+eXLVkaDNcTTJ9+R3a9eTgwI7yX/rnz01MjccXL1m3bEpPJNrYUG/XG6xml90TD4R8vp4OmzMUXJlMtLc3uFuic2avXnvBtJYWN4CyZm8yP6HN6fQF0hNdbr+f+QcgY1rMcSbJCiK3If4uRttYGrcOpzyVkHUnZLFUFHXYKLZiLYjYwN697D0IHKATWaEIBrvTWIihg9l0wLRGEVARllQE7QgThMoOE4laM0Wwbdfqxt5iNOlk2Bu8YSqNTNy0Ok91tW6rf/lMi15PD2T6OyJO+N+fySMeVvLTdvRd1ErB97nkkY9v14jt/qbFDyxaciAc6c9M6K3zR9kbPDrU39LRwsIBJbpXl9JtJxPJJDKbLCJryEayg9xAryaYe5xaki9LyMtLxeWXwWjI8kHg55Usgr4hJc8rFdPrrsG6mK6E/IUUxmEBYTsS8paSvEP1qr6YkNtPyN2l4WR3+5gVTZbkbkuhH2RiQUleYCmshbOhkjxkYcGdSEnehtbYVhq+LjJdj8Gwwo2VoM9P/rJLtYg6i6wfKbiFT+SGkR/++eC/PYLNBXeDHsNB9SOFWrhTN0Ke1ulr6+ob3FXL95lrZve620VrIZEGDdgvDvOaLiZbC6zF1oGlqBbXisNT+5azUP6QdXjCiktYAnW6mDdYHE3eq7Zs3/kFbIhYC6FrMOKxaDlMb3dOnicejrQnQpOnq8m7w+A4kZ3X4QUvFjVNffjdDmtB2wh2c8cW6ILNynyuSnLKBrLq0qBkO5kRjIZ5p0uNMamsgUAZhDdOs3Z4HMMgTrsTYTOGkjFH4GQhKbs2YE+D18KEGy6ZEIfSnexOtegHv5qFUkpXD6zpPvL7lRqr1UFz9QMdc9avn9O3VqOcmvfb73WvG9jZFTe9oDylbFP+9QVLW2ZtS2KJp23CpIVP0OB3n6TBJ55Q3nryu8pb26bFE9N6V3pbzV13/0uXudVrHvzB0UH6L9MugVba0Z5vb8/TgY5YbkK78JWBqwdWG+hLzppazawJE9d/bf3qvm7li7WrBq8eyK5oTE689d3du39/a7KzcXkm0dTfE8q9cuLpoaHDGzbC+ycre3tX9t4f85q7uszemHlw8H3Wwl+PP9Fe/vGUec0dLZMI1qVwGIOWiAd8wzuI3JiQ21KytlTUNqKYaikwdgtj3tpS1XE8U6pTX5Lr1cismKyk7QJqhUer6kLqeZj1RlasVJNjir1Q247soG0EC9sQCrPpFp82mC31zT4/skGtVTbm1PIwtbajh/qcLocummGlHDyLcYUzriy7PYX6WfUS+Lu6xAUJzYvU+aLmG+vhlNKX7tr7Er9w/TfwQveS8h8/4xcee8WfSPjpe7f96NnbNrR3rAzE4wGlec9zP73tf3XEj+O9Xx2746c/qdbr6DCvHSJTmL/oLMkeFm1ATzHMKCGWZFEtPACvMALjbRQxOF+LI/Q4mRVTS1Uq4QKsKOOI3UWzzmTWRTuRt3QGGgnoME0hgHtfLSSjJEKHhPDesIYOhed0ZsLKG8qb4Y0hLPZgeUvpGJab0dX01qGIsk/I5wU6FBmaA8/RSDiMGAhzf8+C39vL6rDU6j5iM2htGZeBZh2UN2glehVnU+4u/5kz063lD4WH6Ta67eHyR5Sz043lPyt3062cWfka/ygNKt9XXuYP0OXKy8qRcnb7OppSSuu2Kz/hfkxnKW8pB/kXaFo5qPwG7QTWwmCtk5U4yLgCGFuiEqSi4rklL5Xxw8iwxgXLk6oDHdqHNSz70P5wwKlarPMLsnyroYR1VMCOHHx7bQLrjUjBgHVaOrU4xQVYmAdQjaZLgi8pS5KU50dOA9ODZwRoUSpX6ge12F+B1JJ6ghWOWBkDU25EZi+YWKcN1C/SM+WAGEIrY+3KEFgNHi4VuBQyeNU/Vm/D+KeZhMnFjIMcjIOQfSIs0KCyDwaogiU5OBZeAPkp+ICRhusEuwf9i4agaD1c69A0hcIsguBxwDVmV/3hasHiWYECK3gNYELTcS5gophLxlKczT+iGvDnNT/avPlHyqfKO8qnPxJXPPj6B68/uEI90G9LtPUivvCZh+CMM5x5Cg7KQ/QNZYVyYgVRa8W0qD+A7MTLZkUoYe4ea0StCbkGa4sKts9MO6koWo6c3E/J/pNlwoopEWBgWPI04fepZZRn6FhDGkkbuapaQRnDqpJirBmVVCwKSqo+AVxQ0BiSrJRQl6RyOxNRtZaSA8qqcWMMAoZKxQmY5CQTPPDJkKWgZYSXDRbsKYa/4tVSukzKwV4irQb5QGb9oIeEdOdkqrJwIJIBFkYuAoABQ/iU9Gd4FogbZcG7iFtyRyLpCFhVCYQS/j6FZ/E+x566KB2JuBUCz7jH1WpVxtxJ7quOOZOQ0ykspjl3rNnzjvWcYXVV8ELDR19CYCCn4yY5NVJo03wit4+QYlt7CtHAMBzTYzhAqwFma4pEWya0MubLmEG+Erl/Sp2UfzLnpS4Pb9eBzo6CQbb9YyKBKaK8089zkrbd7W7SbXzq8+nF+VwcRzmNEcjWpIPnaYHUnkW3asQzQVIkSyaTqWQ6OVKlZFOiEOpIpVgx3kSgoi9RbEl3p6DFD6yRmYLYrS1R6MpDS3upkJsG1+cS/YJxRG8CmeV8cK+5VBACeLRguLzQ0gbn0VKhFQssohZmFNNdcJ4qFTon4ZEVWRS0eTifWiroe/E4NmEz/ikf2qCVh1f1+Hnnn0d56Tx/5yc7Kk+qas1zirDHtzP/mw7SQd31uusBVxDaw2WxAis5lWKlINVFAmaqtbt0UQrqabDW3tVB7/jd4fCGyOFI5DDXfDg8FDkcDh/+nbLzghV0sD29UL0fPhwZCh8un8Sn8JF34H6SjKv/tsGvzWcWx4VzzDStl2laNdbtVvVrM9abYmxbI5gsCDkMiE5IwYUlmaac3CQOU1JjUFVruodLejnw8iiLbcep1YLV0xaCzFxRiZvpf0mK+PXv73z9wfCZwmmhv6I1d37/64oo0f/avOJBjlf2Ysk02FlWOsef1Xc/WVvtvZdVzVXGEDh3DMHKGA7jGLy+84zCKw4TR00Dq5ezygYcVpG67Syy/I9GxWMd/j8e2a2c9M8Gp6iMcPb4JpDhceMLM10WTBa9TIt7W8A5bGaRgmY/qOXK2FvHjb0Fo4koTnIgWYyyGEQ0DJ9qieJpCxa3RMcoFEPpAwrJQk6OikVXE0vfua0FDdZO/P8j1ljE7Z8RrRoe+x+Q7qxYlgAS1KYn2uOkjtVYxpBLahKytYTJuWjFFrIFGUAvcMs9J8YlvMBLbMcclwd4pUbk670sgzNBPGQUrM0BptGjCC90JkeTH9c/YM2Ex4cDFymiCgCLCCqiPOCCZGcW0Cr4VDrO0ulzWrQ+axUQnbqC1tA2WrOGfqpor1D+Wzmu/PeaP9Jt81741fNz6U7lroff3vhCv1DJbu1nsEkg9NS67dvXKhpFs24bYMpTyl3zBwbm0R10+yOL5pc/VB8+yVVhFWDaKi0QzzYCLVIkzzxyoIBBpUA6gXUypNDcCi6GpUnMsenOG4nO7HJ7wpF2LO+VBWtRa7XlquME51LHBkZdZuqiUcr8TRqxZbFsAdUXkiEYsFEni76y8e77t2/fvW4LDEu586PbwhdpyEWj7Sf3t3UqbSY33sCB//k2ei0jyL5/u5QeN8FtddSX3h1fNB8/9yZ+rjyw/6RJaessH7k7juP/863KbUgTehk93tm2/yRR6w05ieHUGkIMHGbTDBS8B06ieWUE3mheUkbYmzLCk7Ov2TNErbdktQ416AvQsS+R+PzoCLzxeWl0hL2NjgDIPeuaPYMyLVUwXw1orHZyC8EqCUR5rmSyaGbCbDaBWIqOBjSkrNC8YAwzm8pkOg4uQbXm3AI8aivJtupqIcwa1LNEbSEBfGsBtFHkAkEMo7vsWMMzQV37YgDGbcPFMJwhx9zFcAVcahyIeMf/U7O0RDWczGwi0OzPUAQeZJRUrB5aOGxAJIJY7DRxoxlkWVWpTLiRcn78C9oFcxpxHbN3hHrB57kXcDAxgGtFeaqpwdbfHKFv0jeP0N+UDx8+JNyoPF1+n85VDnEuOodyrvL7aL9Uv0aCqTWSVpaf0QGVQMQ11fovdLaFEq6IKegxYEYxHm3gdLggBiuWJOQNaRTr7UF1CPCFoEUUcFHU8v8xPx+1iQFXwhgoWwpE0ZHhySm4AyOEMeJ6mnKeB3IoqL8FNtcj2hH4nJ7VqeFnhSzNoozgSwJHbWQUGQ01VvsqbmCVMg/f4ZMjvKTkR+EbMCmg3ivX4XvFR4Rvhm/1MVTGw4gNTNeDx2VE+eWJqEZyKVv0gz0m6kBxSRgu1ygzl64ssSGOszU6tsahF6tHCqbGFKsf0TN30YZpX7bogZ4o6G3AkipSNldX1bDCqka2BgIoPBYIEtkyAH+aC8EpAE03dfgtHAlRsuXAFvivVtacJuC+HztG99KFtOmnm06TXyjfUSKchT2CU6OW3hyjq18Bv4ls+qnyH8r3lG3HqEDfoEt/gWMgYHt1f9Q9xWhdX/FG7Uy7m6HjDQk0b5iLiGRpD3W6qBM9aFvKVu3q/G3LuI9zDz44ifv7sm0HP/kjd0NqOK38helbSl7eK7x+8fTpF38a2/uyhi2tGz1c1a38WG2JlURInFxKEHg0lIoNGLMnDU4wryDoTSU5jnHI1lJloaAZhbpo1uBD5loMBCcScssJuU0NAbW1YJi+IaBhtqapGUQ22qaWUfhR7zpd6AlGWcESVwnJsaVLWlZKlq36ihLt7KdTnrv5/WXhOUORHQ/sP3nl3KHw1of2nwQu/3m/8pPnbv7Dcko5NiGgY8l3j69ZHh6aG9l2cr+yZmhOeDs6lthI6TY2I6SyPoytdYpiVWIEC+2wUNtaKlrZUiYr5jhgCnxqBfpY9KuJrU1DBXZGbemZI88K0s1NoLY07gjaHrtYqG3G5CFYnAYW8NKLhRq2nqbWigqM5tSot2h3+s6sWGKxr1TFvawsaQKu5ghbjgfdB80jwQGvlE8QPvB5VPK4TIlTlyepLuXzSjdecQTvlCW2ZI/VEgFH3qNFeTERJ8w3Lj1D7ewaVwRhV7EUKOSC3YJDEmpzLBdWAUV2LYavquVXVKogoOULlPXK+gUHKwsHxxDPB68tUIbovgW0pPztKN5U7doqtGuat1E9oWJx0SC3SnqbjqB7IfikEY6sKiN/wqTqsb/qukLvuJWqmoqAj4WBcF3VmQWDevIxUV+0srL0zPs4/0EkIfAfqsE9ISkbS0UjW+ZmBHsma6BBNU6+khxKFut9rGy/CW5Zkyz8x9YI8rmCrx6OQXWNoDUb9YtRTOpaXWIkxFGxGSQ3k+aiolPAikmdi5JrN/yOk/4wa8GvDx5SfvM4L9le71sI5zT0ONwRyIPUteF3ZekPfT+4UlY+jCmnvCfojPJRDp/74TqZ2mJU1/y68sOjDyrvb/idmqvhgaYCrsF0VOmEQS0hUdCMLROkkoDqG4lAqnYIJwHp21KN5ejUaJhepQmWWOE3oJY2jH1RmNkgAQwQLrvE4NooOptobQa4vJ5o/h2+0cbQ680Ew0IupjyaWG6kOYlrHUHu/EkMP9eqS+W04wv9zpQqqTIXUIFtuFqkVCtaMeVeCCBaaPI2I48WeBfc0Zsd9erSg2GDyd6gJuCBwxCwd6Z7aNJL7SYaiFRxrKFyb4Du3KL8N/2qNDL41ae+OohvrVsf3rr1Yfpo9Q6f5/b3KM1gMcn6yiODgzSHD21VpLF7Z9klXKGcJEhTdYWykfEtx9Yp47pkdSlyQUMA7uiNcCZUlAPFhXb+RnpG0aMx5NlS1zL5yxkdz401KtLZGt6g4rbKOmnVk6hGRu5ns13L1mm5U3IOy/2wii6Qkqew7FU+Ibem5GklOcJW5iRY700p6Dqu5+1UNcf4gAgMZpgTm0IhVxJtiA8DIXBmwRhUoRujHZNLwwZzTy8+MFldK6oGPAqTu2DgWAOlclcF1zEuCzr8maC1Gj38zNE6DuHZxq8qPwvtAbbBSEaEQbdx/y8ah/suomxhMb4wFoIQ8FNQRYAGRx9jj9PIWYc32GF0XDBErS8FzIXx6kaSIGhVeLY4iGeGhTdgRpQ3ob1sYhoXjUgJK/3RvGN0sbIiiyW7wPtMVXKe0r4hne7o7i9fkji6bf9Jl6tSGcjtO77PE9x9dNUVu07u7+lVF6Gjjsc8hqBG/4GHopH0VLVcz26mJhoFRwKj4y/SOXPe7z8+h3rhOOdYv5KjByg5cBoRpQ/vHu9/f84c5Z3+1/rfn83NUnL8L0+TA8xBpYggNeia6VAn69g4eVVlVMp1q7qiast5Nd5bjfKqueXXNB9q/hVUtHtsbaohoSJBXHYqa9SkELosUabelO8spR8qtqV0Ka5KXzqo2BTbIF0K9sRGX9NK7LuA6bPUD5+KQuOHS5XvoH6iS5fyI+xZ/BjLK+S12H/0LtEjghbAlGB/yiMCAOE8O2PPoZ3K43OAvQ3sgxz4V3klzxMuXwYva0TJj9WU89BJsNciKcIFTDOgUYGRATxOXl2gTkFDQzc/5zmQeVTQ6lL2qp+gkdi2DVZWG43+ri6ByAP9ARa6YQj5U+gjR9RSX2RGC15oJC05a6+H80VJv4/UL1p8HSm2Wr8o+iei4AqJoj2UxjbAeo5wBtv0iWJ9Sxe2GQAkTshhW22i2NTGIql1paKnHSOpFJUHOVEU1L0i+FJRazSxM+b9Fe31TXhlKxWdbi87YzmRYkhVGcFSMYLR0yRmSABQFtNd3UkWQC12TuqBs8K0yn4SZ4Kenw2C/k+uOSL94z9OOnsDijL5f7tmLMGxXBPLC6EOnsryQiD5jVgXUN2zomlc+bJYjeGDFkX470Gbh1Ere+6cTFoggstXqgaCw3X9akoNa43VXTVUG0HUVBuuYNpHh3gyOj5vpfZPC7IcIV8i2JlACZExgqEIA0N6QDwqpGCl2MU6G1vgb0ZdFlXXkyN2kuuSiJSM6qYFLFeMdcahBAbyCj4jrivTaDm1ulgWwGQTIxN0meKlXIdYSo1+G2gGADLYAL8jmDl7yKExe6hu/wC+Jg5VGj/4SpoOvQK4f5qwPSKYaIyRYX/VDWLxDbXOBXNaDVg/ZgSPIIUOokNdx2ms5u60NZhrKWq0SAANNcSKWg3Lm2OBE4AXK9xvKFVXdfrtBD32CMFpwxH4K0c0Mspbb50mbylvsTlib4L0nvJIu/IXWtdOL6XrKAtFoE1Sj5X1AES1Mc0wW4tJMYKrV7zgtqWq1sb7WWsDM+Q/ARPBZiHkB1tbE0G85I0AePL5Q+ih8GKxkQVd/qEpwlL/gIYdKNBbq/2MVcK9OBRpiA5RhrsBFIG29/nG2yi1YBDe1PGcsZkBXA/sYwPxgngki16Gtr1sIF6E4z6LOkRco6AuTfD6YDAuwvpfoM5/2ntM6TJ7em7PWXcRvimqZf1sr1VOw/xnJXZjAI18NbNcGuaR4HYemAUt1rLitloLkt42tsXI+OScheHaosWMD1rAg0a3i+XdipzRipEvtuYC49UCNurVRtwKRhZVAdHhJGRFA9o6DEVjtyT0cDAIFFEugpPyG5yKfShj/ze5MJ4/Vn6D8dFYHlcgRtJVHYdRtcM1n+l2JRKFPZQ56JVRI46JKmXOgOhHg0PBcPEqHZHB4Uri1LUm3JiMiaAFZxIMIjhwmTRKlzY1TguCX6BlmsRWGjZqcVeWehYNMTKoVDCCp1VwNuTOKEMxGNDiogsH6IZORISRdBYjflhfwKrB8qPq0gsebMfoKxlVGX6KGkJCLZC9J8vWIZEDulW6VeAXd+K8Rlh5VqcahckCxDkhd5TkDgurJnWzzGqhg8e0vEZfO6EddVpaHLaE6tjSEbf1sOiob2oOshhIEgTtsIf4Qy24x4ncKQ5TTT1uqCGbrYe1xjqLzaX6KVmsZIpmNZ1ZPusCzJZ18U5X2IV1TjqXLqzV2XRYzhjVRW2RqKaq9w/8Qa//wyQ6MdHtuOOl6ZbpL93p7ErRiZNYs/Jq21QnNBv001+6w9GVUl7lIgyFcX+sNnYnzvcwfony6qTKd0M7Z6yAN/6s/ZfYbKo7MLnHrNnYnkYudQcmnDkXOG2HcQcm0c6o4jYj9bQ6YnWcswsT27EoS7U22skWEJ6zG1OSth2/9QvlGbPK3NFZyvHjt52zL1PyuHJ8Fnf0izRVnrHrtuO07Zx+byIon+D9mJn3Y8QobKW+pIJHm5jmr2Wrprlk0cjKHI2o6o0WNAg65vagodYn2Rh16MKZbKCQRLFgBqll7ipu08SwLC41dWDyyFLBxdUCNNQvAsjvKGK/is0+zA5azLOi/yKQU79gJqu/arjOyDBivCZS9dnVgJWgUv6Mz872E2ABY9XJQcj4qRqPIWNxAO/ZsYPq15XGBRFQflSPX40zs32OJLZfGa5P01U+VMGo+AmbGsmFIai/qwLWcZ/lznyWRw0w9lnKdoFSd9ZSt3Eqs2+o7PNExu/zRKr7PPGUbVSir2KuaZW9Sf7/oS46DnWdKWQaZeuEkTAV+IHICm+cUmGXhpzKjIu9Vvqo4q4bSLEJ+/j/iLx045DX58CuELDkIU6jFZqZ1J0XcdmqiMtf+Xd+xFXdb0tSR3n6rJFzn4VcZdx4ipkBtbDr1HjUdbYsukgH0yF2dY+PsRmqT7C949REkA7tvFkEg5T7nD3b+JQYPHfftiLrV2xk5LMqgn+PdWYU+nlWf8xj/bGx/piYZR/fH5Or2p/a8/VnfHj+3P58+0zs5rM9EpLj4zfj+4R5zytZnxIlrLv2sB2R1OwnatumUrGJ7UHSZMNUugWjkyj+uIFAE+CGw7yxtq6NmamI+LRBMLfGO1JqbVmqOpbW847Fxcriseod/3loCivlqxX0wYD1c8fJrfzymkiju74+c0Gj+2XROmMgHF685KuHas87dP74oT6L2Bhsagy0trdNywU8dkd7ZtKkhZunTTuTsmBreNWcBagrm8jyWgA5VKEDXvPRt1mC6O1znsWkEjwrsN0GcZdB+rbiUz/B8l7VfBnm5KzECTKJ1HawiJcJdD83tilbTRJj5hgXRtWQsvltNGhLRYM2dp6iPJzDbw/SxYMgBo4TMWmkcgmC8Ue41LCYdBmVAOKlsYtKXlHViaCy3Jir7bRGQmYajQgfW7Zwt3G3bbH8XHltyyOPbFFe09yhPD9UfpC7Yoh2/0kc+vrXh0Tmz5C19KTuAW0zKHgD7h9po1nepmbvMPlrW0s7Xj927HW66WNKPqb3vE4TyrHXfykQJbeX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Prostaglandin E2 Archives | Hair Loss Cure 2020 In a number of past posts, I have discussed how hair loss is impacted by prostaglandins (lipids). Most of my focus has been on how a reduction in prostaglandin D2 (PGD2 ) levels benefits hair growth. In this post, I will discuss how an increase in levels of prostaglandin E2 (PGE2) and PGF2a (PGF2α) leads to hair growth.
Increase PGE2 and PGF2a for hair growth. Reduce PGD2. It has also been hypothesized that the balance between PGE2 and PGD2 levels controls hair growth. Increased levels of PGD2 and reduced levels of PGE2 have been observed in the scalps of men suffering from androgenetic alopecia (AGA). Also of note, PGE2 is known to act synergistically with PGF2 alpha
PGE2 and Hair Growth PGE2 (also known as dinoprostone) is a naturally occurring prostaglandin that is also known to interact with Wnt signaling . A number of studies have shown that increasing PGE2 levels on the scalp can benefit hair growth.
An interesting 2019 study found that one of the ways in which skin and tissue injury can sometimes lead to hair growth is via an increase in PGE2.
A 2018 case report from Spain found that the drug Omeprazole induced hypertrichosis (excessive body hair) in two children. This side effect resulted from a significant increase in prostaglandin E2 levels. Once Omeprazole therapy was stopped, the excess body hair entirely disappeared after six months.
One of the ways in which Minoxidil works to grow hair is via increasing PGE2 levels.
Dexamethasone and Sulfasalazine can both increase prostaglandin E2 levels significantly.
Natural products such as castor oil are thought to raise PGE2 levels, and potentially benefit hair growth. Even if true, such gains will be modest at best in my opinion.
PGF2α (aka PGF2a) and Hair PGF2α acts by binding to the prostaglandin F2α receptor. When injected into the body or amniotic sac, PGF2α can either induce labor or cause an abortion in a pregnant woman. PGF2a levels are higher in people with non-balding scalps.
In the past, I have written in detail about the glaucoma drug Bimatoprost . This drug is an analog of prostamide F2a, which is almost the same as prostaglandin F2a. Bimatoprost raises both PGF2a and PGE2 levels, and is therefore the key ingredient in eyelash hair growth drug Latisse.
Another analogue of prostaglandin F2a is the well known drug Latanaprost. It prolongs the anagen phase of the hair cycle via the prostaglandin effect .
Another glaucoma and high eye pressure relief drug named Travoprost has a patent related to its scalp hair growth properties. Travaprost raises both PGF2α and PGE2 levels on the scalp when applied topically.
The only other major PGF2a analogue pharmaceutical on the market is called Carboprost.
Hair loss news first:
— The biggest news so far this month is Allergan’s purchase of Kythera Biopharmaceuticals yesterday. While Allergan is largely known for its blockbuster Botox product, for us hair loss sufferers, the company’s Bimatoprost product is is all we care about. While Kythera’s most well known product is its recently approved ATX-101 (brand name Kybella) china fat reducing topical product, for us hair loss sufferers, the company’s Setipiprant product is all we care about.
Bimatoprost is essentially (but not exactly) a prostaglandin E2 (PGE2 ) analog and Setipiprant is a prostaglandin D2 (PGD2 ) antagonist. The latter holds far greater potential to be a cure for hair loss compared to the former. A combination treatment with the two drugs (i.e, increase PGE2 and decrease PGD2) has in the past been postulated to be the perfect treatment to regrow hair. I would urge all blog readers to listen to this encouraging audio segment on Setipiprant from an investor call earlier this year.
— An interesting article on a doctor in Texas using PRP with stem cells derived from a donor’s placenta to treat hair loss.
— The renowned Dr. John Cole is planning to do a major study on the effectiveness of platelet-rich plasma (PRP) therapy. The PRP treatment will entail three sessions (once a month for three months) costing a total of $750, an absolute steal. Moreover, it seems like Dr. Cole will refund that $750 too if you show up for a follow-up 6-12 months after the first injection session. Dr. Cole will test many different treatment protocols, including using a variety of extracellular matrix (ECM) products and activation methods.
PRP is still fairly new when it comes to the hair loss world, with many significant differences in methodology and ingredients existing between different doctors and hair transplant surgeons. Such a study needed to be done a few years ago. If you do volunteer for this study, please make sure you know exactly what Dr. Cole will inject into your scalp. He is very well respected and unlikely to do anything even remotely risky, but when you are injecting something into your scalp (or for that matter, anywhere into your body), it is best to be very cautious.
And now on to medical items of interest:
— A new study finds that keeping PGE2 levels high in mice by reducing 15-PGDH promotes tissue regeneration. It seems like PGE2 has many benefits besides hair growth.
— A groundbreaking new $25 blood test called VirScan that can tell you every virus you have had. An average person has been exposed to 10 of the 206 known viruses that infect humans.
— A great article on the history of artificial hearts and continuing progress.
— An update on the patient who might get a full body transplant (always inaccurately referred to as a head transplant by the media).
— Since I already covered the above story several times this year, the one on a Chinese surgeon who has performed 1,000 head transplants in mice and plans to move on to monkeys next is more interesting, albeit revolting and slightly discouraging (the mice usually only survived for minutes, with the record being 10 days). The excellent WSJ article with a video on this requires a subscription, but if you google the article’s title, you will then be able to access it without a subscription. I did not realize the now obvious conclusion that a full body transplant would be revolutionary when it comes to most types of cancer treatment. However, even I do not foresee a successful long-lasting full body transplant in a human for many decades to come. Nevertheless, what an insane era we are living through.
Hair loss news blog. Hair cloning for baldness.