����JFIFXX�����    $.' ",#(7),01444'9=82<.342  2!!22222222222222222222222222222222222222222222222222����"��4�� ���,�PG"Z_�4�˷����kjز�Z�,F+��_z�,�© �����zh6�٨�ic�fu���#ډb���_�N�?��wQ���5-�~�I���8����TK<5o�Iv-�����k�_U_�����~b�M��d����Ӝ�U�Hh��?]��E�w��Q���k�{��_}qFW7HTՑ��Y��F�?_�'ϔ��_�Ջt��=||I ��6�έ"�����D���/[�k�9���Y�8ds|\���Ҿp6�Ҵ���]��.����6�z<�v��@]�i%��$j��~�g��J>��no����pM[me�i$[����s�o�ᘨ�˸ nɜG-�ĨU�ycP�3.DB�li�;��hj���x7Z^�N�h������N3u{�:j�x�힞��#M&��jL P@_���� P��&��o8������9�����@Sz6�t7#O�ߋ �s}Yf�T���lmr����Z)'N��k�۞p����w\�Tȯ?�8`�O��i{wﭹW�[�r�� ��Q4F�׊���3m&L�=��h3����z~��#�\�l :�F,j@�� ʱ�wQT����8�"kJO���6�֚l����}���R�>ډK���]��y����&����p�}b��;N�1�m�r$�|��7�>e�@B�TM*-iH��g�D�)� E�m�|�ؘbҗ�a��Ҿ����t4���o���G��*oCN�rP���Q��@z,|?W[0�����:�n,jWiE��W��$~/�hp\��?��{(�0���+�Y8rΟ�+����>S-S����VN;�}�s?.����� w�9��˟<���Mq4�Wv'��{)0�1mB��V����W[�����8�/<� �%���wT^�5���b��)iM� pg�N�&ݝ��VO~�q���u���9� ����!��J27����$O-���! �:�%H��� ـ����y�ΠM=t{!S�� oK8������t<����è:a������[�����ա�H���~��w��Qz`�po�^ ����Q��n� �,uu�C�$ ^���,������8�#��:�6��e�|~���!�3�3.�\0��q��o�4`.|� ����y�Q�`~;�d�ׯ,��O�Zw�������`73�v�܋�<���Ȏ�� ـ4k��5�K�a�u�=9Yd��$>x�A�&�� j0� ���vF��� Y�|�y��� ~�6�@c��1vOp�Ig����4��l�OD���L����� R���c���j�_�uX6��3?nk��Wy�f;^*B� ��@�~a�`��Eu������+���6�L��.ü>��}y���}_�O�6�͐�:�YrG�X��kG�����l^w���~㒶sy��Iu�!� W ��X��N�7BV��O��!X�2����wvG�R�f�T#�����t�/?���%8�^�W�aT��G�cL�M���I��(J����1~�8�?aT ���]����AS�E��(��*E}� 2��#I/�׍qz��^t�̔���b�Yz4x���t�){ OH��+(E��A&�N�������XT��o��"�XC��'���)}�J�z�p� ��~5�}�^����+�6����w��c��Q�|Lp�d�H��}�(�.|����k��c4^�"�����Z?ȕ ��a<�L�!039C� �Eu�C�F�Ew�ç ;�n?�*o���B�8�bʝ���'#Rqf���M}7����]����s2tcS{�\icTx;�\��7K���P���ʇ Z O-��~��c>"��?�������P��E��O�8��@�8��G��Q�g�a�Վ���󁶠�䧘��_%#r�>�1�z�a��eb��qcPѵ��n���#L��� =��׀t� L�7�`��V���A{�C:�g���e@�w1 Xp3�c3�ġ����p��M"'-�@n4���fG��B3�DJ�8[Jo�ߐ���gK)ƛ��$���� ���8�3�����+���� �����6�ʻ���� ���S�kI�*KZlT _`���?��K����QK�d����B`�s}�>���`��*�>��,*@J�d�oF*����弝��O}�k��s��]��y�ߘ��c1G�V���<=�7��7����6�q�PT��tXԀ�!9*4�4Tހ3XΛex�46���Y��D ����� �BdemDa����\�_l,��G�/���֌7���Y�](�xTt^%�GE�����4�}bT���ڹ�����;Y)���B�Q��u��>J/J �⮶.�XԄ��j�ݳ�+E��d ��r�5�_D�1 ��o�� �B�x�΢�#���<��W�����8���R6�@g�M�.��� dr�D��>(otU��@x=��~v���2� ӣ�d�oBd��3�eO�6�㣷�����ݜ6��6Y��Qz`��S��{���\P�~z m5{J/L��1������<�e�ͅPu�b�]�ϔ���'������f�b� Zpw��c`"��i���BD@:)ִ�:�]��hv�E�w���T�l��P���"Ju�}��وV J��G6��. J/�Qgl߭�e�����@�z�Zev2u�)]կ�����7x���s�M�-<ɯ�c��r�v�����@��$�ޮ}lk���a���'����>x��O\�ZFu>�����ck#��&:��`�$�ai�>2Δ����l���oF[h��lE�ܺ�Πk:)���`�� $[6�����9�����kOw�\|���8}������ބ:��񶐕��I�A1/�=�2[�,�!��.}gN#�u����b��� ~��݊��}34q����d�E��Lc��$��"�[q�U�硬g^��%B �z���r�pJ�ru%v\h1Y�ne`ǥ:g���pQM~�^�Xi� ��`S�:V29.�P���V�?B�k�� AEvw%�_�9C�Q����wKekPؠ�\�;Io d�{ ߞo�c1eP����\� `����E=���@K<�Y���eڼ�J���w����{av�F�'�M�@/J��+9p���|]�����Iw &`��8���&M�hg��[�{��Xj��%��Ӓ�$��(����ʹN���<>�I���RY���K2�NPlL�ɀ)��&e����B+ь����( � �JTx���_?EZ� }@ 6�U���뙢ط�z��dWI�n` D����噥�[��uV��"�G&Ú����2g�}&m��?ċ�"����Om#��������� ��{�ON��"S�X��Ne��ysQ���@Fn��Vg���dX�~nj�]J�<�K]:��FW��b�������62�=��5f����JKw��bf�X�55��~J �%^����:�-�QIE��P��v�nZum� z � ~ə ���� ���ة����;�f��\v���g�8�1��f24;�V���ǔ�)����9���1\��c��v�/'Ƞ�w�������$�4�R-��t���� e�6�/�ġ �̕Ecy�J���u�B���<�W�ַ~�w[B1L۲�-JS΂�{���΃������A��20�c#��@ 0!1@AP"#2Q`$3V�%45a6�FRUq��� ����^7ׅ,$n�������+��F�`��2X'��0vM��p�L=������5��8������u�p~���.�`r�����\���O��,ư�0oS ��_�M�����l���4�kv\JSd���x���SW�<��Ae�IX����������$I���w�:S���y���›R��9�Q[���,�5�;�@]�%���u�@ *ro�lbI �� ��+���%m:�͇ZV�����u�̉����θau<�fc�.����{�4Ա� �Q����*�Sm��8\ujqs]{kN���)qO�y�_*dJ�b�7���yQqI&9�ԌK!�M}�R�;������S�T���1���i[U�ɵz�]��U)V�S6���3$K{�ߊ<�(� E]Զ[ǼENg�����'�\?#)Dkf��J���o��v���'�%ƞ�&K�u�!��b�35LX�Ϸ��63$K�a�;�9>,R��W��3�3� d�JeTYE.Mϧ��-�o�j3+y��y^�c�������VO�9NV\nd�1 ��!͕_)a�v;����թ�M�lWR1��)El��P;��yوÏ�u 3�k�5Pr6<�⒲l�!˞*��u־�n�!�l:����UNW ��%��Chx8vL'��X�@��*��)���̮��ˍ��� ���D-M�+J�U�kvK����+�x8��cY������?�Ԡ��~3mo��|�u@[XeY�C�\Kp�x8�oC�C�&����N�~3-H���� ��MX�s�u<`���~"WL��$8ξ��3���a�)|:@�m�\���^�`�@ҷ)�5p+��6���p�%i)P M���ngc�����#0Aruz���RL+xSS?���ʮ}()#�t��mˇ!��0}}y����<�e� �-ή�Ԩ��X������ MF���ԙ~l L.3���}�V뽺�v�����멬��Nl�)�2����^�Iq��a��M��qG��T�����c3#������3U�Ǎ���}��לS�|qa��ڃ�+���-��2�f����/��bz��ڐ�� �ݼ[2�ç����k�X�2�* �Z�d���J�G����M*9W���s{��w���T��x��y,�in�O�v��]���n����P�$�JB@=4�OTI�n��e�22a\����q�d���%�$��(���:���: /*�K[PR�fr\nڙdN���F�n�$�4�[�� U�zƶ����� �mʋ���,�ao�u 3�z� �x��Kn����\[��VFmbE;�_U��&V�Gg�]L�۪&#n%�$ɯ�dG���D�TI=�%+AB�Ru#��b4�1�»x�cs�YzڙJG��f��Il��d�eF'T� iA��T���uC�$����Y��H?����[!G`}���ͪ� �纤Hv\������j�Ex�K���!���OiƸ�Yj�+u-<���'q����uN�*�r\��+�]���<�wOZ.fp�ێ��,-*)V?j-kÊ#�`�r��dV����(�ݽBk�����G�ƛk�QmUڗe��Z���f}|����8�8��a���i��3'J�����~G_�^���d�8w������ R�`(�~�.��u���l�s+g�bv���W���lGc}��u���afE~1�Ue������Z�0�8�=e�� f@/�jqEKQQ�J��oN��J���W5~M>$6�Lt�;$ʳ{���^��6�{����v6���ķܰg�V�cnn �~z�x�«�,2�u�?cE+Ș�H؎�%�Za�)���X>uW�Tz�Nyo����s���FQƤ��$��*�&�LLXL)�1�" L��eO��ɟ�9=���:t��Z���c��Ž���Y?�ӭV�wv�~,Y��r�ۗ�|�y��GaF�����C�����.�+� ���v1���fήJ�����]�S��T��B��n5sW}y�$��~z�'�c ��8 ��� ,! �p��VN�S��N�N�q��y8z˱�A��4��*��'������2n<�s���^ǧ˭P�Jޮɏ�U�G�L�J�*#��<�V��t7�8����TĜ>��i}K%,���)[��z�21z ?�N�i�n1?T�I�R#��m-�����������������1����lA�`��fT5+��ܐ�c�q՝��ʐ��,���3�f2U�եmab��#ŠdQ�y>\��)�SLY����w#��.���ʑ�f��� ,"+�w�~�N�'�c�O�3F�������N<���)j��&��,-� �љ���֊�_�zS���TǦ����w�>��?�������n��U仆�V���e�����0���$�C�d���rP �m�׈e�Xm�Vu� �L��.�bֹ��� �[Դaզ���*��\y�8�Է:�Ez\�0�Kq�C b��̘��cө���Q��=0Y��s�N��S.���3.���O�o:���#���v7�[#߫ ��5�܎�L���Er4���9n��COWlG�^��0k�%<���ZB���aB_���������'=��{i�v�l�$�uC���mƎҝ{�c㱼�y]���W�i ��ߧc��m�H� m�"�"�����;Y�ߝ�Z�Ǔ�����:S#��|}�y�,/k�Ld� TA�(�AI$+I3��;Y*���Z��}|��ӧO��d�v��..#:n��f>�>���ȶI�TX��� 8��y����"d�R�|�)0���=���n4��6ⲑ�+��r<�O�܂~zh�z����7ܓ�HH�Ga롏���nCo�>������a ���~]���R���̲c?�6(�q�;5%� |�uj�~z8R=X��I�V=�|{v�Gj\gc��q����z�؋%M�ߍ����1y��#��@f^���^�>N�����#x#۹��6�Y~�?�dfPO��{��P�4��V��u1E1J �*|���%���JN��`eWu�zk M6���q t[�� ��g�G���v��WIG��u_ft����5�j�"�Y�:T��ɐ���*�;� e5���4����q$C��2d�}���� _S�L#m�Yp��O�.�C�;��c����Hi#֩%+) �Ӎ��ƲV���SYź��g |���tj��3�8���r|���V��1#;.SQ�A[���S������#���`n�+���$��$I �P\[�@�s��(�ED�z���P��])8�G#��0B��[ى��X�II�q<��9�~[Z멜�Z�⊔IWU&A>�P~�#��dp<�?����7���c��'~���5 ��+$���lx@�M�dm��n<=e�dyX��?{�|Aef ,|n3�<~z�ƃ�uۧ�����P��Y,�ӥQ�*g�#먙R�\���;T��i,��[9Qi歉����c>]9�� ��"�c��P�� �Md?٥��If�ت�u��k��/����F��9�c*9��Ǎ:�ØF���z�n*�@|I�ށ9����N3{'��[�'ͬ�Ҳ4��#}��!�V� Fu��,�,mTIk���v C�7v���B�6k�T9��1�*l� '~��ƞF��lU��'�M ����][ΩũJ_�{�i�I�n��$���L�� j��O�dx�����kza۪��#�E��Cl����x˘�o�����V���ɞ�ljr��)�/,�߬h�L��#��^��L�ф�,íMƁe�̩�NB�L�����iL����q�}��(��q��6IçJ$�W�E$��:������=#����(�K�B����zђ <��K(�N�۫K�w��^O{!����)�H���>x�������lx�?>Պ�+�>�W���,Ly!_�D���Ō�l���Q�!�[ �S����J��1��Ɛ�Y}��b,+�Lo�x�ɓ)����=�y�oh�@�꥟/��I��ѭ=��P�y9��� �ۍYӘ�e+�p�Jnϱ?V\SO%�(�t� ���=?MR�[Ș�����d�/ ��n�l��B�7j� ��!�;ӥ�/�[-���A�>�dN�sLj ��,ɪv��=1c�.SQ�O3�U���ƀ�ܽ�E����������̻��9G�ϷD�7(�}��Ävӌ\�y�_0[w ���<΍>����a_��[0+�L��F.�޺��f�>oN�T����q;���y\��bՃ��y�jH�<|q-eɏ�_?_9+P���Hp$�����[ux�K w�Mw��N�ی'$Y2�=��q���KB��P��~������Yul:�[<����F1�2�O���5=d����]Y�sw:���Ϯ���E��j,_Q��X��z`H1,#II ��d�wr��P˂@�ZJV����y$�\y�{}��^~���[:N����ߌ�U�������O��d�����ؾe��${p>G��3c���Ė�lʌ�� ת��[��`ϱ�-W����dg�I��ig2��� ��}s ��ؤ(%#sS@���~���3�X�nRG�~\jc3�v��ӍL��M[JB�T��s3}��j�Nʖ��W����;7��ç?=X�F=-�=����q�ߚ���#���='�c��7���ڑW�I(O+=:uxq�������������e2�zi+�kuG�R��������0�&e�n���iT^J����~\jy���p'dtG��s����O��3����9* �b#Ɋ�� p������[Bws�T�>d4�ۧs���nv�n���U���_�~,�v����ƜJ1��s�� �QIz��)�(lv8M���U=�;����56��G���s#�K���MP�=��LvyGd��}�VwWBF�'�à �?MH�U�g2�� ����!�p�7Q��j��ڴ����=��j�u��� Jn�A s���uM������e��Ɔ�Ҕ�!)'��8Ϣ�ٔ��ޝ(��Vp���צ֖d=�IC�J�Ǡ{q������kԭ�߸���i��@K����u�|�p=..�*+����x�����z[Aqġ#s2a�Ɗ���RR�)*HRsi�~�a &f��M��P����-K�L@��Z��Xy�'x�{}��Zm+���:�)�) IJ�-i�u���� ���ܒH��'�L(7�y�GӜq���� j��� 6ߌg1�g�o���,kر���tY�?W,���p���e���f�OQS��!K�۟cҒA�|ս�j�>��=⬒��˧L[�� �߿2JaB~R��u�:��Q�] �0H~���]�7��Ƽ�I���(}��cq '�ήET���q�?f�ab���ӥvr� �)o��-Q��_'����ᴎo��K������;��V���o��%���~OK ����*��b�f:���-ťIR��`B�5!RB@���ï�� �u �̯e\�_U�_������� g�ES��3�������QT��a����x����U<~�c?�*�#]�MW,[8O�a�x��]�1bC|踤�P��lw5V%�)�{t�<��d��5���0i�XSU��m:��Z�┵�i�"��1�^B�-��P�hJ��&)O��*�D��c�W��vM��)����}���P��ܗ-q����\mmζZ-l@�}��a��E�6��F�@��&Sg@���ݚ�M����� ȹ 4����#p�\H����dYDo�H���"��\��..R�B�H�z_�/5˘����6��KhJR��P�mƶi�m���3�,#c�co��q�a)*Pt����R�m�k�7x�D�E�\Y�閣_X�<���~�)���c[[�BP����6�Yq���S��0����%_����;��Àv�~�| VS؇ ��'O0��F0��\���U�-�d@�����7�SJ*z��3n��y��P����O���������m�~�P�3|Y��ʉr#�C�<�G~�.,! ���bqx���h~0=��!ǫ�jy����l�O,�[B��~��|9��ٱ����Xly�#�i�B��g%�S��������tˋ���e���ې��\[d�t)��.+u�|1 ������#�~Oj����hS�%��i.�~X���I�H�m��0n���c�1uE�q��cF�RF�o���7� �O�ꮧ� ���ۛ{��ʛi5�rw?׌#Qn�TW��~?y$��m\�\o����%W� ?=>S�N@�� �Ʈ���R����N�)�r"C�:��:����� �����#��qb��Y�. �6[��2K����2u�Ǧ�HYR��Q�MV��� �G�$��Q+.>�����nNH��q�^��� ����q��mM��V��D�+�-�#*�U�̒ ���p욳��u:�������IB���m���PV@O���r[b= �� ��1U�E��_Nm�yKbN�O���U�}�the�`�|6֮P>�\2�P�V���I�D�i�P�O;�9�r�mAHG�W�S]��J*�_�G��+kP�2����Ka�Z���H�'K�x�W�MZ%�O�YD�Rc+o��?�q��Ghm��d�S�oh�\�D�|:W������UA�Qc yT�q������~^�H��/��#p�CZ���T�I�1�ӏT����4��"�ČZ�����}��`w�#�*,ʹ�� ��0�i��課�Om�*�da��^gJ݅{���l�e9uF#T�ֲ��̲�ٞC"�q���ߍ ոޑ�o#�XZTp����@ o�8��(jd��xw�]�,f���`~�|,s��^����f�1���t��|��m�򸄭/ctr��5s��7�9Q�4�H1꠲BB@l9@���C�����+�wp�xu�£Yc�9��?`@#�o�mH�s2��)�=��2�.�l����jg�9$�Y�S�%*L������R�Y������7Z���,*=�䷘$�������arm�o�ϰ���UW.|�r�uf����IGw�t����Zwo��~5 ��YյhO+=8fF�)�W�7�L9lM�̘·Y���֘YLf�큹�pRF���99.A �"wz��=E\Z���'a� 2��Ǚ�#;�'}�G���*��l��^"q��+2FQ� hj��kŦ��${���ޮ-�T�٭cf�|�3#~�RJ����t��$b�(R��(����r���dx� >U b�&9,>���%E\� Ά�e�$��'�q't��*�א���ެ�b��-|d���SB�O�O��$�R+�H�)�܎�K��1m`;�J�2�Y~9��O�g8=vqD`K[�F)k�[���1m޼c��n���]s�k�z$@��)!I �x՝"v��9=�ZA=`Ɠi �:�E��)`7��vI��}d�YI�_ �o�:ob���o ���3Q��&D&�2=�� �Ά��;>�h����y.*ⅥS������Ӭ�+q&����j|UƧ����}���J0��WW< ۋS�)jQR�j���Ư��rN)�Gű�4Ѷ(�S)Ǣ�8��i��W52���No˓� ۍ%�5brOn�L�;�n��\G����=�^U�dI���8$�&���h��'���+�(������cȁ߫k�l��S^���cƗjԌE�ꭔ��gF���Ȓ��@���}O���*;e�v�WV���YJ\�]X'5��ղ�k�F��b 6R�o՜m��i N�i����>J����?��lPm�U��}>_Z&�KK��q�r��I�D�Չ~�q�3fL�:S�e>���E���-G���{L�6p�e,8��������QI��h��a�Xa��U�A'���ʂ���s�+טIjP�-��y�8ۈZ?J$��W�P� ��R�s�]��|�l(�ԓ��sƊi��o(��S0��Y� 8�T97.�����WiL��c�~�dxc�E|�2!�X�K�Ƙਫ਼�$((�6�~|d9u+�qd�^3�89��Y�6L�.I�����?���iI�q���9�)O/뚅����O���X��X�V��ZF[�یgQ�L��K1���RҖr@v�#��X�l��F���Нy�S�8�7�kF!A��sM���^rkp�jP�DyS$N���q��nxҍ!U�f�!eh�i�2�m���`�Y�I�9r�6� �TF���C}/�y�^���Η���5d�'��9A-��J��>{�_l+�`��A���[�'��յ�ϛ#w:݅�%��X�}�&�PSt�Q�"�-��\縵�/����$Ɨh�Xb�*�y��BS����;W�ջ_mc�����vt?2}1�;qS�d�d~u:2k5�2�R�~�z+|HE!)�Ǟl��7`��0�<�,�2*���Hl-��x�^����'_TV�gZA�'j� ^�2Ϊ��N7t�����?w�� �x1��f��Iz�C-Ȗ��K�^q�;���-W�DvT�7��8�Z�������� hK�(P:��Q- �8�n�Z���܃e貾�<�1�YT<�,�����"�6{/ �?�͟��|1�:�#g��W�>$����d��J��d�B��=��jf[��%rE^��il:��B���x���Sּ�1հ��,�=��*�7 fcG��#q� �eh?��2�7�����,�!7x��6�n�LC�4x��},Geǝ�tC.��vS �F�43��zz\��;QYC,6����~;RYS/6���|2���5���v��T��i����������mlv��������&� �nRh^ejR�LG�f���? �ۉҬܦƩ��|��Ȱ����>3����!v��i�ʯ�>�v��オ�X3e���_1z�Kȗ\<������!�8���V��]��?b�k41�Re��T�q��mz��TiOʦ�Z��Xq���L������q"+���2ۨ��8}�&N7XU7Ap�d�X��~�׿��&4e�o�F��� �H����O���č�c�� 懴�6���͉��+)��v;j��ݷ�� �UV�� i��� j���Y9GdÒJ1��詞�����V?h��l����l�cGs�ځ�������y�Ac�����\V3�? �� ܙg�>qH�S,�E�W�[�㺨�uch�⍸�O�}���a��>�q�6�n6����N6�q������N ! 1AQaq�0@����"2BRb�#Pr���3C`��Scst���$4D���%Td�� ?���N����a��3��m���C���w��������xA�m�q�m���m������$����4n淿t'��C"w��zU=D�\R+w�p+Y�T�&�պ@��ƃ��3ޯ?�Aﶂ��aŘ���@-�����Q�=���9D��ռ�ѻ@��M�V��P��܅�G5�f�Y<�u=,EC)�<�Fy'�"�&�չ�X~f��l�KԆV��?�� �W�N����=(� �;���{�r����ٌ�Y���h{�١������jW����P���Tc�����X�K�r��}���w�R��%��?���E��m�� �Y�q|����\lEE4���r���}�lsI�Y������f�$�=�d�yO����p�����yBj8jU�o�/�S��?�U��*������ˍ�0������u�q�m [�?f����a�� )Q�>����6#������� ?����0UQ����,IX���(6ڵ[�DI�MNލ�c&���υ�j\��X�R|,4��� j������T�hA�e��^���d���b<����n�� �즇�=!���3�^�`j�h�ȓr��jẕ�c�,ٞX����-����a�ﶔ���#�$��]w�O��Ӫ�1y%��L�Y<�wg#�ǝ�̗`�x�xa�t�w��»1���o7o5��>�m뭛C���Uƃߜ}�C���y1Xνm�F8�jI���]����H���ۺиE@I�i;r�8ӭ����V�F�Շ| ��&?�3|x�B�MuS�Ge�=Ӕ�#BE5G�����Y!z��_e��q�р/W>|-�Ci߇�t�1ޯќd�R3�u��g�=0 5��[?�#͏��q�cf���H��{ ?u�=?�?ǯ���}Z��z���hmΔ�BFTW�����<�q�(v� ��!��z���iW]*�J�V�z��gX֧A�q�&��/w���u�gYӘa���; �i=����g:��?2�dž6�ى�k�4�>�Pxs����}������G�9��3 ���)gG�R<>r h�$��'nc�h�P��Bj��J�ҧH� -��N1���N��?��~��}-q!=��_2hc�M��l�vY%UE�@|�v����M2�.Y[|y�"Eï��K�ZF,�ɯ?,q�?v�M 80jx�"�;�9vk�����+ ֧�� �ȺU��?�%�vcV��mA�6��Qg^M����A}�3�nl� QRN�l8�kkn�'�����(��M�7m9و�q���%ޟ���*h$Zk"��$�9��: �?U8�Sl��,,|ɒ��xH(ѷ����Gn�/Q�4�P��G�%��Ա8�N��!� �&�7�;���eKM7�4��9R/%����l�c>�x;������>��C�:�����t��h?aKX�bhe�ᜋ^�$�Iհ �hr7%F$�E��Fd���t��5���+�(M6�t����Ü�UU|zW�=a�Ts�Tg������dqP�Q����b'�m���1{|Y����X�N��b �P~��F^F:����k6�"�j!�� �I�r�`��1&�-$�Bevk:y���#yw��I0��x��=D�4��tU���P�ZH��ڠ底taP��6����b>�xa����Q�#� WeF��ŮNj�p�J* mQ�N����*I�-*�ȩ�F�g�3 �5��V�ʊ�ɮ�a��5F���O@{���NX��?����H�]3��1�Ri_u��������ѕ�� ����0��� F��~��:60�p�͈�S��qX#a�5>���`�o&+�<2�D����: �������ڝ�$�nP���*)�N�|y�Ej�F�5ټ�e���ihy�Z �>���k�bH�a�v��h�-#���!�Po=@k̆IEN��@��}Ll?j�O������߭�ʞ���Q|A07x���wt!xf���I2?Z��<ץ�T���cU�j��]��陎Ltl �}5�ϓ��$�,��O�mˊ�;�@O��jE��j(�ا,��LX���LO���Ц�90�O �.����a��nA���7������j4 ��W��_ٓ���zW�jcB������y՗+EM�)d���N�g6�y1_x��p�$Lv:��9�"z��p���ʙ$��^��JԼ*�ϭ����o���=x�Lj�6�J��u82�A�H�3$�ٕ@�=Vv�]�'�qEz�;I˼��)��=��ɯ���x �/�W(V���p�����$ �m�������u�����񶤑Oqˎ�T����r��㠚x�sr�GC��byp�G��1ߠ�w e�8�$⿄����/�M{*}��W�]˷.�CK\�ުx���/$�WPw���r� |i���&�}�{�X� �>��$-��l���?-z���g����lΆ���(F���h�vS*���b���߲ڡn,|)mrH[���a�3�ר�[1��3o_�U�3�TC�$��(�=�)0�kgP���� ��u�^=��4 �WYCҸ:��vQ�ר�X�à��tk�m,�t*��^�,�}D*� �"(�I��9R����>`�`��[~Q]�#af��i6l��8���6�:,s�s�N6�j"�A4���IuQ��6E,�GnH��zS�HO�uk�5$�I�4��ؤ�Q9�@��C����wp�BGv[]�u�Ov���0I4���\��y�����Q�Ѹ��~>Z��8�T��a��q�ޣ;z��a���/��S��I:�ܫ_�|������>=Z����8:�S��U�I�J��"IY���8%b8���H��:�QO�6�;7�I�S��J��ҌAά3��>c���E+&jf$eC+�z�;��V����� �r���ʺ������my�e���aQ�f&��6�ND��.:��NT�vm�<- u���ǝ\MvZY�N�NT��-A�>jr!S��n�O 1�3�Ns�%�3D@���`������ܟ 1�^c<���� �a�ɽ�̲�Xë#�w�|y�cW�=�9I*H8�p�^(4���՗�k��arOcW�tO�\�ƍR��8����'�K���I�Q�����?5�>[�}��yU�ײ -h��=��% q�ThG�2�)���"ו3]�!kB��*p�FDl�A���,�eEi�H�f�Ps�����5�H:�Փ~�H�0Dت�D�I����h�F3�������c��2���E��9�H��5�zԑ�ʚ�i�X�=:m�xg�hd(�v����׊�9iS��O��d@0ڽ���:�p�5�h-��t�&���X�q�ӕ,��ie�|���7A�2���O%P��E��htj��Y1��w�Ѓ!����  ���� ࢽ��My�7�\�a�@�ţ�J �4�Ȼ�F�@o�̒?4�wx��)��]�P��~�����u�����5�����7X ��9��^ܩ�U;Iꭆ 5 �������eK2�7(�{|��Y׎ �V��\"���Z�1� Z�����}��(�Ǝ"�1S���_�vE30>���p;� ΝD��%x�W�?W?v����o�^V�i�d��r[��/&>�~`�9Wh��y�;���R��� ;;ɮT��?����r$�g1�K����A��C��c��K��l:�'��3 c�ﳯ*"t8�~l��)���m��+U,z��`(�>yJ�?����h>��]��v��ЍG*�{`��;y]��I�T� ;c��NU�fo¾h���/$���|NS���1�S�"�H��V���T���4��uhǜ�]�v;���5�͠x��'C\�SBpl���h}�N����� A�Bx���%��ޭ�l��/����T��w�ʽ]D�=����K���ž�r㻠l4�S�O?=�k �M:� ��c�C�a�#ha���)�ѐxc�s���gP�iG��{+���x���Q���I= �� z��ԫ+ �8"�k�ñ�j=|����c ��y��CF��/��*9ж�h{ �?4�o� ��k�m�Q�N�x��;�Y��4膚�a�w?�6�>e]�����Q�r�:����g�,i"�����ԩA�*M�<�G��b�if��l^M��5� �Ҩ�{����6J��ZJ�����P�*�����Y���ݛu�_4�9�I8�7���������,^ToR���m4�H��?�N�S�ѕw��/S��甍�@�9H�S�T��t�ƻ���ʒU��*{Xs�@����f�����֒Li�K{H�w^���������Ϥm�tq���s� ���ք��f:��o~s��g�r��ט� �S�ѱC�e]�x���a��) ���(b-$(�j>�7q�B?ӕ�F��hV25r[7 Y� }L�R��}����*sg+��x�r�2�U=�*'WS��ZDW]�WǞ�<��叓���{�$�9Ou4��y�90-�1�'*D`�c�^o?(�9��u���ݐ��'PI&� f�Jݮ�������:wS����jfP1F:X �H�9dԯ���˝[�_54 �}*;@�ܨ�� ð�yn�T���?�ןd�#���4rG�ͨ��H�1�|-#���Mr�S3��G�3�����)�.᧏3v�z֑��r����$G"�`j �1t��x0<Ɔ�Wh6�y�6��,œ�Ga��gA����y��b��)��h�D��ß�_�m��ü �gG;��e�v��ݝ�nQ� ��C����-�*��o���y�a��M��I�>�<���]obD��"�:���G�A��-\%LT�8���c�)��+y76���o�Q�#*{�(F�⽕�y����=���rW�\p���۩�c���A���^e6��K������ʐ�cVf5$�'->���ՉN"���F�"�UQ@�f��Gb~��#�&�M=��8�ט�JNu9��D��[̤�s�o�~������ G��9T�tW^g5y$b��Y'��س�Ǵ�=��U-2 #�MC�t(�i� �lj�@Q 5�̣i�*�O����s�x�K�f��}\��M{E�V�{�υ��Ƈ�����);�H����I��fe�Lȣr�2��>��W�I�Ȃ6������i��k�� �5�YOxȺ����>��Y�f5'��|��H+��98pj�n�.O�y�������jY��~��i�w'������l�;�s�2��Y��:'lg�ꥴ)o#'Sa�a�K��Z� �m��}�`169�n���"���x��I ��*+� }F<��cГ���F�P�������ֹ*�PqX�x۩��,� ��N�� �4<-����%����:��7����W���u�`����� $�?�I��&����o��o��`v�>��P��"��l���4��5'�Z�gE���8���?��[�X�7(��.Q�-��*���ތL@̲����v��.5���[��=�t\+�CNܛ��,g�SQnH����}*F�G16���&:�t��4ُ"A��̣��$�b �|����#rs��a�����T�� ]�<�j��BS�('$�ɻ� �wP;�/�n��?�ݜ��x�F��yUn�~mL*-�������Xf�wd^�a�}��f�,=t�׵i�.2/wpN�Ep8�OР���•��R�FJ� 55TZ��T �ɭ�<��]��/�0�r�@�f��V��V����Nz�G��^���7hZi����k��3�,kN�e|�vg�1{9]_i��X5y7� 8e]�U����'�-2,���e"����]ot�I��Y_��n�(JҼ��1�O ]bXc���Nu�No��pS���Q_���_�?i�~�x h5d'�(qw52] ��'ޤ�q��o1�R!���`ywy�A4u���h<קy���\[~�4�\ X�Wt/� 6�����n�F�a8��f���z �3$�t(���q��q�x��^�XWeN'p<-v�!�{�(>ӽDP7��ո0�y)�e$ٕv�Ih'Q�EA�m*�H��RI��=:��� ���4牢) �%_iN�ݧ�l]� �Nt���G��H�L��� ɱ�g<���1V�,�J~�ٹ�"K��Q�� 9�HS�9�?@��k����r�;we݁�]I�!{ �@�G�[�"��`���J:�n]�{�cA�E����V��ʆ���#��U9�6����j�#Y�m\��q�e4h�B�7��C�������d<�?J����1g:ٳ���=Y���D�p�ц� ׈ǔ��1�]26؜oS�'��9�V�FVu�P�h�9�xc�oq�X��p�o�5��Ա5$�9W�V(�[Ak�aY錎qf;�'�[�|���b�6�Ck��)��#a#a˙��8���=äh�4��2��C��4tm^ �n'c���]GQ$[Wҿ��i���vN�{Fu ��1�gx��1┷���N�m��{j-,��x�� Ūm�ЧS�[�s���Gna���䑴�� x�p 8<������97�Q���ϴ�v�aϚG��Rt�Һ׈�f^\r��WH�JU�7Z���y)�vg=����n��4�_)y��D'y�6�]�c�5̪�\� �PF�k����&�c;��cq�$~T�7j ���nç]�<�g ":�to�t}�159�<�/�8������m�b�K#g'I'.W�����6��I/��>v��\�MN��g���m�A�yQL�4u�Lj�j9��#44�t��l^�}L����n��R��!��t��±]��r��h6ٍ>�yҏ�N��fU�� ���� Fm@�8}�/u��jb9������he:A�y�ծw��GpΧh�5����l}�3p468��)U��d��c����;Us/�֔�YX�1�O2��uq�s��`hwg�r~�{ R��mhN��؎*q 42�*th��>�#���E����#��Hv�O����q�}�����6�e��\�,Wk�#���X��b>��p}�դ��3���T5��†��6��[��@�P�y*n��|'f�֧>�lư΂�̺����SU�'*�q�p�_S�����M�� '��c�6�����m�� ySʨ;M��r���Ƌ�m�Kxo,���Gm�P��A�G�:��i��w�9�}M(�^�V��$ǒ�ѽ�9���|���� �a����J�SQ�a���r�B;����}���ٻ֢�2�%U���c�#�g���N�a�ݕ�'�v�[�OY'��3L�3�;,p�]@�S��{ls��X�'���c�jw�k'a�.��}�}&�� �dP�*�bK=ɍ!����;3n�gΊU�ߴmt�'*{,=SzfD� A��ko~�G�aoq�_mi}#�m�������P�Xhύ����mxǍ�΂���巿zf��Q���c���|kc�����?���W��Y�$���_Lv����l߶��c���`?����l�j�ݲˏ!V��6����U�Ђ(A���4y)H���p�Z_�x��>���e��R��$�/�`^'3qˏ�-&Q�=?��CFVR �D�fV�9��{�8g�������n�h�(P"��6�[�D���< E�����~0<@�`�G�6����Hг�cc�� �c�K.5��D��d�B���`?�XQ��2��ٿyqo&+�1^� DW�0�ꊩ���G�#��Q�nL3��c���������/��x ��1�1[y�x�პCW��C�c�UĨ80�m�e�4.{�m��u���I=��f�����0QRls9���f���������9���~f�����Ǩ��a�"@�8���ȁ�Q����#c�ic������G��$���G���r/$W�(��W���V�"��m�7�[m�A�m����bo��D� j����۳� l���^�k�h׽����� ��#� iXn�v��eT�k�a�^Y�4�BN��ĕ��0 !01@Q"2AaPq3BR������?���@4�Q�����T3,���㺠�W�[=JK�Ϟ���2�r^7��vc�:�9 �E�ߴ�w�S#d���Ix��u��:��Hp��9E!�� V 2;73|F��9Y���*ʬ�F��D����u&���y؟��^EA��A��(ɩ���^��GV:ݜDy�`��Jr29ܾ�㝉��[���E;Fzx��YG��U�e�Y�C���� ����v-tx����I�sם�Ę�q��Eb�+P\ :>�i�C'�;�����k|z�رn�y]�#ǿb��Q��������w�����(�r|ӹs��[�D��2v-%��@;�8<a���[\o[ϧw��I!��*0�krs)�[�J9^��ʜ��p1)� "��/_>��o��<1����A�E�y^�C��`�x1'ܣn�p��s`l���fQ��):�l����b>�Me�jH^?�kl3(�z:���1ŠK&?Q�~�{�ٺ�h�y���/�[��V�|6��}�KbX����mn[-��7�5q�94�������dm���c^���h� X��5��<�eޘ>G���-�}�دB�ޟ� ��|�rt�M��V+�]�c?�-#ڛ��^ǂ}���Lkr���O��u�>�-D�ry� D?:ޞ�U��ǜ�7�V��?瓮�"�#���r��չģVR;�n���/_� ؉v�ݶe5d�b9��/O��009�G���5n�W����JpA�*�r9�>�1��.[t���s�F���nQ� V 77R�]�ɫ8����_0<՜�IF�u(v��4��F�k�3��E)��N:��yڮe��P�`�1}�$WS��J�SQ�N�j�ٺ��޵�#l���ј(�5=��5�lǏmoW�v-�1����v,W�mn��߀$x�<����v�j(����c]��@#��1������Ǔ���o'��u+����;G�#�޸��v-lη��/(`i⣍Pm^���ԯ̾9Z��F��������n��1��� ��]�[��)�'������:�֪�W��FC����� �B9،!?���]��V��A�Վ�M��b�w��G F>_DȬ0¤�#�QR�[V��kz���m�w�"��9ZG�7'[��=�Q����j8R?�zf�\a�=��O�U����*oB�A�|G���2�54 �p��.w7� �� ��&������ξxGHp� B%��$g�����t�Џ򤵍z���HN�u�Я�-�'4��0��;_��3 !01"@AQa2Pq#3BR������?��ʩca��en��^��8���<�u#��m*08r��y�N"�<�Ѳ0��@\�p��� �����Kv�D��J8�Fҽ� �f�Y��-m�ybX�NP����}�!*8t(�OqѢ��Q�wW�K��ZD��Δ^e��!� ��B�K��p~�����e*l}z#9ң�k���q#�Ft�o��S�R����-�w�!�S���Ӥß|M�l޶V��!eˈ�8Y���c�ЮM2��tk���� ������J�fS����Ö*i/2�����n]�k�\���|4yX�8��U�P.���Ы[���l��@"�t�<������5�lF���vU�����W��W��;�b�cД^6[#7@vU�xgZv��F�6��Q,K�v��� �+Ъ��n��Ǣ��Ft���8��0��c�@�!�Zq s�v�t�;#](B��-�nῃ~���3g������5�J�%���O������n�kB�ĺ�.r��+���#�N$?�q�/�s�6��p��a����a��J/��M�8��6�ܰ"�*������ɗud"\w���aT(����[��F��U՛����RT�b���n�*��6���O��SJ�.�ij<�v�MT��R\c��5l�sZB>F��<7�;EA��{��E���Ö��1U/�#��d1�a�n.1ě����0�ʾR�h��|�R��Ao�3�m3 ��%�� ���28Q� ��y��φ���H�To�7�lW>����#i`�q���c����a��� �m,B�-j����݋�'mR1Ήt�>��V��p���s�0IbI�C.���1R�ea�����]H�6����������4B>��o��](��$B���m�����a�!=��?�B� K�Ǿ+�Ծ"�n���K��*��+��[T#�{E�J�S����Q�����s�5�:�U�\wĐ�f�3����܆&�)����I���Ԇw��E T�lrTf6Q|R�h:��[K�� �z��c֧�G�C��%\��_�a�84��HcO�bi��ؖV��7H �)*ģK~Xhչ0��4?�0��� �E<���}3���#���u�?�� ��|g�S�6ꊤ�|�I#Hڛ� �ա��w�X��9��7���Ŀ%�SL��y6č��|�F�a 8���b��$�sק�h���b9RAu7�˨p�Č�_\*w��묦��F ����4D~�f����|(�"m���NK��i�S�>�$d7SlA��/�²����SL��|6N�}���S�˯���g��]6��; �#�.��<���q'Q�1|KQ$�����񛩶"�$r�b:���N8�w@��8$�� �AjfG|~�9F ���Y��ʺ��Bwؒ������M:I岎�G��`s�YV5����6��A �b:�W���G�q%l�����F��H���7�������Fsv7��k�� 403WebShell
403Webshell
Server IP : 104.21.45.146  /  Your IP : 108.162.242.51
Web Server : Apache/2.4.52 (Ubuntu)
System : Linux ip-172-31-19-221 6.8.0-1029-aws #31~22.04.1-Ubuntu SMP Thu Apr 24 21:16:18 UTC 2025 x86_64
User : www-data ( 33)
PHP Version : 8.1.28
Disable Function : NONE
MySQL : OFF  |  cURL : ON  |  WGET : ON  |  Perl : ON  |  Python : OFF  |  Sudo : ON  |  Pkexec : ON
Directory :  /efsdata/authorproof.omicsgroup.co.in/paper-submissions-new/2020/Oct/21/

Upload File :
current_dir [ Writeable ] document_root [ Writeable ]

 

Command :


[ Back ]     

Current File : /efsdata/authorproof.omicsgroup.co.in/paper-submissions-new/2020/Oct/21/body-q1r1-1603285719.doc
��ࡱ�>��	ko����j�������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������[�	���=bjbj����	4jΐΐ�5��������
�
�����������$)1����������0�0�0�0�0�0�0$�3�o6X�0�������0������0V"V"V"�B�����0V"��0V"V"V�$@j%���������� .%�0�00)1:%0�6�!X�6j%j%:�6��%�
��V"������0�0V"���)1�������������������������������������������������������������������������6����������
	�:	Journal of Molecular Biomarkers & Diagnosis
Short name: J Mol Biomark Diagn
Volume 11: 6, 2020
CSF Lactate an Independent and Reliable Biomarker among the CSF Parameters to Differntiate Bacterial Meningitis from Aseptic Meningitis
Karthika Remash1*, Ravi Raj1 , Gopala Krishna M. Pillai2, Gireesh Kumar K.P3, Lakshmi A1, Atthulya Mangal1
�Department of Internal Medicine, Amrita Institute of Medical Sciences, Kochi, Kerala, India
2Department of General Medicine, Amrita Institute of Medical Sciences, Kochi, Kerala, India
3Department of Emergency Medicine, Amrita Institute of Medical Sciences Kochi, Kerala, India
Abstract
Objective: To compare the mean values of CSF parameters (lactate, protein, sugar, ADA) and thereby distinguish between cases of bacterial and non-bacterial meningitis.
Materials and methods: A cross sectional study was conducted in which 60 adult patients were included and CSF parameters (differential counts, protein, sugar, ADA, lactate) were in analyzed in 22 patients of bacterial meningitis and 38 patients of aseptic meningitis. Data were analyzed using SPSS version 21.0. Descriptive statistics are represented using frequencies and percentages. Analytical statistics were represented using Chi-square test for the comparison of categorical variables. The mean values were compared using independent t- test.
Results: Among the other CSF parameters, the mean value of CSF lactate and CSF sugars were found to have significant difference (p-value 0.01) in bacterial and non-bacterial meningitis. With a cut off value of 3 mmol/l, CSF lactate was useful in differentiating bacterial meningitis from aseptic meningitis. However other parameters including CSF protein and CSF ADA did not show significant difference between bacterial meningitis including TBM and non-bacterial meningitis, whereas CSF lactate also showed significant difference in TBM and viral meningitis. It was also found out that mortality is proportionately increased with the increasing lactate levels.
Conclusion: This study concludes that CSF lactate is an important, independent and reliable biomarker with a cut off value of 3mmol/L, to differentiate bacterial meningitis including TBM from nonbacterial meningitis. TBM and viral meningitis are difficult to differentiate due to their similar clinical features and lab parameters. In such cases, CSF lactate can be taken as a reliable differentiating marker. CSF lactate can be used when CSF gram stain and cultures are inconclusive and time consuming. Thus, helps in initiating early treatment and achieving better outcomes.
Keywords: CSF Parameter � Biomarker � Meningitis � Chi-square test � TBM
*Address for Correspondence: Remash K, Department of Internal Medicine, Amrita Institute of Medical Sciences, Kochi, Kerala, India, E-mail: karthikaremash92@gmail.com
Copyright: � 2020 Remash K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 11 July, 2020; Accepted: 14 October, 2020; Published: 21 October, 2020
Introduction
Meningitis is one of the serious medical conditions which caused high mortality and morbidity. At the same time, early diagnosis and treatment can produce a good quality of life. Even with the advancement in molecular technology, the diagnosis is continued to be a medical challenge. A combination of present CSF variables (proteins, glucose, leucocytes count, and the ratio of CSF/serum glucose) has been suggested effective in differentiating non-bacterial meningitis from bacterial meningitis [1,2].However, there are serious limitations of the above variables in diagnosing and differentiating bacterial and non-bacterial meningitis [1]. The CSF lactate concentration has been suggested as a useful parameter to differentiate bacterial from aseptic meningitis. Meningitis is one of the reasons for prolonged hospitalization. Considering the huge disease burden, there is a necessity of a cost-effective and reliable marker. CSF lactate is one such marker.  CSF lactate in bacterial meningitis originates from different sources. Bacterial pathogens themselves produce varying amounts of lactate; accounting for 10% of the total CSF lactate [1,4]. Bacterial meningitis is associated with generalized brain edema, causing a reduction of global cerebral blood flow and inflammatory involvement of vasculature, with loss of autoregulatory mechanisms, vasospasm, and thrombosis. This leads to cerebral ischemia and consequently to glycolysis by means of anaerobic metabolism [1,5].  In addition, cytokines that flood the brain in meningitis reduce tissue oxygen uptake and causes a shift toward anaerobic metabolism, thus increasing lactate production. Cytokines also mediate invasion of neutrophils into the subarachnoid space, which may also contribute to the rise in CSF lactate level by glycolysis in bacterial meningitis [1,6]. Tubercular meningitis (TBM) is the most serious form of neurotuberculosis. India is among the nations with a high incidence of TB. Usually, there are 20% of extra pulmonary cases of which, 15% are neurotuberculosis [7]. CSF lactate level is easy to estimate and cost-effective. There are few studies that addressed the diagnostic value of the CSF lactate in bacterial meningitis or differentiating bacterial from viral meningitis and tuberculous meningitis. This study aimed to compare the mean values of CSF parameters (Lactate, protein, sugar, ADA) and thereby distinguish between cases of bacterial and non-bacterial meningitis.
Materials and Methods
A cross-sectional study conducted in the Department of General Medicine and the Department of Neurology at Amrita Institute of Medical Sciences, Kochi, Kerala including 60 adult patients above 18 years with clinical features of meningitis for a period of 18 months (November 2018 to May 2020) while patients with coagulopathy, mitochondrial diseases, and pregnant patients were excluded. The study was approved by the institutional ethical committee and informed consent was taken from the patients. The sample size required with 80% power and 99.9% confidence was 4 per group. However, the authors could analyze 60 patients in the mentioned study period. History and physical examination were recorded in the study proforma. The CSF sample was collected on the first spinal tap conducted in the institution. CSF lactate estimation was done using the calorimetric method.  Based on the other biochemical analysis, patients were further divided into two groups.
Group A patients had clinical symptoms including fever, headache, and signs of meningeal irritation. CSF analysis also showed pleocytosis with segmented and monocytic cells, low glucose, high protein. In Tubercular meningitis, CSF ADA was also high and features like basal exudates and tuberculoma in neuroimaging. The rest of the patients were categorized into group B.
Data were analyzed using SPSS version 21.0.Descriptive statistics were represented using frequencies and percentages. Analytical statistics were represented using Chi-square test for the comparison of categorical variables. Independent sample T-test was applied for comparing the mean CSF lactate level between bacterial and nonbacterial meningitis.
Results
During the study period, 60 patients were included in the study.  40 percent of the study population was between 41- 60 years of age with 37 males and 23 females. Based on the CSF biochemical parameters, 22 patients had bacterial meningitis and 38 patients had nonbacterial meningitis. The cut off value of CSF lactate and CSF sugars were taken as 3mmol/L and 80mg/dl, respectively. Based on this; the patients were divided into two categories. CSF lactate was elevated in 16 cases of bacterial meningitis and 8 cases of non-bacterial meningitis. CSF Glucose was reduced in 20 cases of bacterial meningitis and 17 cases of non-bacterial meningitis. CSF protein and CSF ADA were found to have no association with bacterial meningitis including TBM. The CSF lactate and CSF sugars in bacterial meningitis differed significantly from aseptic meningitis (p value <0.01). Among the two, it was found out that CSF lactate showed more significance. Also, the mortality rate was found to be higher in bacterial meningitis than aseptic meningitis.
Discussion
The therapeutic decision-making of bacterial meningitis is critical due to the highly significant disease associated mortality and morbidity. In our study, we found that CSF lactate is the most prominent biomarker for diagnosing bacterial meningitis. It was also found that lactate concentration increases proportionally to the number of inflammatory cells in CSF. A lactate concentration of 4.2 mmol/L accurately predicted 24 out of 25 bacterial meningitis as per literature [8,9].Unlike glucose, CSF lactate typically remains elevated for a significant time even if after appropriate therapy is initiated. This may help in diagnosing bacterial meningitis, in which antibiotics had been given already [8,10]. Smith et al have reported, CSF lactate as a useful tool in the early diagnosis of bacterial meningitis with high sensitivity (92%) and specificity (99%) as well as in differentiating bacterial from viral meningitis. Klein et al. have also reported that the CSF lactate level has higher reliability than the opposite CSF tests in diagnosing and differentiating bacterial meningitis from viral meningitis. It was also noticed that patients who died had higher CSF lactate level (avg.19.4 mmol/L) than those who were discharged with or without sequelae, an observation which is also reported by the other investigators [11-14]. Another study by Curtis GD et al., observed that in 109 patients of proven bacterial meningitis, the mean lactate concentration was elevated (over 2.8 mol l-1) in all cases [7,11]. Zebba siddiqi et al. reported that CSF lactate had a positive association with both the stage and diagnostic class of TBM than CSF ADA.In this study, there was a significant difference in the CSF lactate among bacterial and nonbacterial meningitis with a p-value of 0.01.
Conclusion
This study concludes that CSF lactate is an important, independent and reliable biomarker with a cut off value of 3mmol/L, to differentiate bacterial meningitis including TBM from nonbacterial meningitis. TBM and viral meningitis are difficult to differentiate due to their similar clinical features and lab parameters. In such cases, CSF lactate can be taken as a reliable differentiating marker. CSF lactate can be used when CSF gram stain and cultures are inconclusive and time consuming. Thus, helps in initiating early treatment and achieving better outcomes.
Limitations
The main limitation of the study was a small sample size and the risk prediction is limited due to the small sample size. Also, the study was not compared to gold standard method of diagnosis.
References
1. Ali Hassan Abro, Ahmed Mohamed Saleh Abdou, Abdulla M Ustadi and Ahmed Alhaj Saleh, et al. �CSF lactate level: a useful diagnostic tool to differentiate acute bacterial and viral meningitis.� J Pak Med Assoc 59 (2009): 508-511.
2. Yasuharu Tokuda. �Bacterial versus viral meningitis: comparison of the old and the new clinical prediction model.� Critic Care 4 (2012): 1-2.
3. Frances Talaska Fischbach and Marshall Barnett. �A manual of laboratory and diagnostic tests.� Lippincott Williams & Wilkins Publishers 7 (2004): 290.
4. Salord Francois, Boussaid Osher, Eynard Nava and Perret Christen, et al. �Value of D(-) Lactate Determination for the Fast Diagnosis of Meningitis after Craniotomy: An Initial Study.� Ann Fr Anesth Reanim 13 (1994): 647-653.
5. Stephen L Leib, Young S. Kim, Stephen M Black and Jay H. Tureen, et al. �Tauber MG. Inducible nitric oxide synthase and the effect of aminogaunidine in experimental neonatal meningitis.� J Infect Dis 177 (1998): 692-700.
6. Vijay Singhal, Zeba Siddiqi, Jalees Fatma and Ritu Karoli, et al. �Cerebrospinal Fluid Lactate in Tubercular Meningitis: Diagnostic or Prognostic Marker.� J Assoc Phys India 66 (2018): 18-27.
7. Pediakkal M Jabir, Valappil V Ashraf and Thekkedath Manojan. �Role of Cerebrospinal Fluid Lactate and C-Reactive Protein in Differential Diagnosis of Meningitis in Adults.� J Clin Diagn Res 13 (2019): OC01-OC04.
8. Eduardo Mekitarian Filho, S�rgio Massaru Horita, Alfredo Elias Gilio and Lise E. Nigrovic. �Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children.� Int J Emerg Med 7 (2014): 14.
9. Hiroaki Yao, Seizou Sadoshima, Yin Nishimura and Kim Fujii, et al. �Cerebrospinal fluid lactate in patients with diabetes mellitus and hypoglycaemic coma.� J Neurol Neurosurg Psychiatry 52 (1989): 372-375.
10. Gordon D W Curtis, Mary Slack and Duke S Tompkins. �Cerebrospinal fluid lactate and the diagnosis of meningitis.� J Infect 3 (1981): 159-165.
11. Sharon M. Smith, Robert H. K. Eng, John M Campos and Herman Chmel. �D-lactic acid measurements in the diagnosis of bacterial infection.� J Clin Microbiol 27 (1989): 385-388.
12. Tilmann O Kleine, Peter Zwerenz, Peter Z�fel and Kiyoshi Shiratori, et al. �New and old diagnostic markers of meningitis in cerebrospinal fluid (CSF).� Brain Res Bull 61 (2003): 287-297.
13. Damman Baird, Hanns C Whittle and Brian M Greenwood. �Mortality from pneumococcal meningitis.� Lancet 2 (1976): 1344-1346.
How to cite this article: Karthika Remash, Ravi Raj , Gopala Krishna M. Pillai and Gireesh KP Kumar, et al. �CSF Lactate an Independent and Reliable Biomarker among the CSF Parameters to Differntiate Bacterial Meningitis from Aseptic Meningitis.� J Mol Biomark Diagn 11 (2020): 438.
+,8KLTUWX^_�DZ�iS:$:+h�f�B*CJOJQJ^JaJmH	@phsH	@1h5S�h@@B*CJOJQJ^JaJmH	@phsH	@+h�V&B*CJOJQJ^JaJmH	@phsH	@+hbrB*CJOJQJ^JaJmH	@phsH	@1h5S�h�2�B*CJOJQJ^JaJmH	@phsH	@1h�V&h�V&B*CJOJQJ^JaJmH	@phsH	@+h];�B*CJOJQJ^JaJmH	@phsH	@7h5S�h�2�5�B*CJOJQJ\�^JaJmH	@phI&msH	@7h�V&h�V&5�B*CJOJQJ\�^JaJmH	@phI&msH	@,L_�R	�	
h
q
>
��������������$d��xa$gd+�$��d���7$8$H$]�^�a$gd��dhgdT&���d���7$8$H$]�^�$
����d���7$8$H$]�^�a$gd�H�$��d���7$8$H$]�^�a$
_klz{������������				2	3	>	?	P	Q	R	S	�	������������������������ucWh+�h+�6�OJQJ#hT&�hB6�B*H*OJQJph�/h�h�2�5�B*OJQJ\�^JmH	@phsH	@!h+�5�B*H*OJPJQJph�'h+�h+�5�B*H*OJPJQJph�h+�h+�5�OJPJQJ4hO!�h�2�5�B*CJ OJQJ^JaJ mH	@phsH	@ h+�5�CJ OJPJQJ\�aJ &h+�h+�5�CJ OJPJQJ\�aJ �	�	�	�	�	�	�	�	�	





`
a
g
h
p
q
{
(������������סׅlZI:h+�5�CJOJPJQJaJ h+�h+�CJOJPJQJaJ#h+�h+�5�CJOJPJQJaJ1h��5�B*CJOJQJ\�^JaJmH	@phsH	@7h5S�h��5�B*CJOJQJ\�^JaJmH	@phsH	@hT&�h+�6�OJQJh+�6�B*H*OJQJph�hT&�6�OJQJ#hT&�hT&�6�B*H*OJQJph�h+�6�OJQJh+�h+�6�OJQJh+�h+�hT&�hT&�6�OJQJ(/��>
F
��#,-/89;EF�������ܲ���t[��[�J hT&�hT&�CJOJPJQJaJ1h��h��B*CJOJQJ^JaJmH	@phsH	@ h�Ph�PCJOJPJQJaJ h�h�CJOJPJQJaJ7h5S�h��5�B*CJOJQJ\�^JaJmH	@phsH	@7h��h��5�B*CJOJQJ\�^JaJmH	@phsH	@h�CJOJPJQJaJ h+�h+�CJOJPJQJaJ#h+�h+�5�CJOJPJQJaJFGHWXYZ]^{���п��И`D+1h�6�B*CJOJQJ]�^JaJmH	@phsH	@7h�h�6�B*CJOJQJ]�^JaJmH	@phsH	@=h5S�h@@5�6�B*CJOJQJ\�]�^JaJmH	@phsH	@1hzrWh��B*CJOJQJ^JaJmH	@phsH	@+h�B*CJOJQJ^JaJmH	@phsH	@ hp�h�PCJOJPJQJaJ h+�h�CJOJPJQJaJ+h�PB*CJOJQJ^JaJmH	@phsH	@1h��h�PB*CJOJQJ^JaJmH	@phsH	@^er'�![#�$�$�(�(�/�/2������������������gd�$$d��xa$gdXKg$d��xa$gdW+�$d��xa$gd�Y$d��xa$gd�K~$��d���7$8$H$]�^�a$$��d���7$8$H$]�^�a$gdzrW����������ﴘy]A(1hT&�6�B*CJOJQJ]�^JaJmH	@phsH	@7h�h�6�B*CJOJQJ]�^JaJmH	@phsH	@7h5S�h@@6�B*CJOJQJ]�^JaJmH	@phsH	@=h5S�h@@5�6�B*CJOJQJ\�]�^JaJmH	@phsH	@7h5S�h�2�6�B*CJOJQJ]�^JaJmH	@phsH	@#h�h�6�CJOJPJQJaJhtA�h��6�CJOJQJaJh�h�6�OJQJh~6�CJOJQJaJhtA�h�#�6�CJOJQJaJ  !%)�ͱ�yaI1+h�r�B*CJOJQJ^JaJmH	@phsH	@.hT&�B*CJOJQJ\�^JaJmH	@phsH	@.h~B*CJOJQJ\�^JaJmH	@phsH	@.ht�B*CJOJQJ\�^JaJmH	@phsH	@7h5S�h@@5�B*CJOJQJ\�^JaJmH	@phsH	@7h5S�h�2�6�B*CJOJQJ]�^JaJmH	@phsH	@7h5S�h@@6�B*CJOJQJ]�^JaJmH	@phsH	@1h�8�6�B*CJOJQJ]�^JaJmH	@phsH	@1h�6�B*CJOJQJ]�^JaJmH	@phsH	@	)+-789:AGITVW^de�д��l�Vд�l�V=1h5S�h�2�B*CJOJQJ^JaJmH	@phsH	@+h�r�B*CJOJQJ^JaJmH	@phsH	@.h~B*CJOJQJ\�^JaJmH	@phsH	@.ht�B*CJOJQJ\�^JaJmH	@phsH	@.h�f�B*CJOJQJ\�^JaJmH	@phsH	@7h5S�h@@5�B*CJOJQJ\�^JaJmH	@phsH	@1h5S�h@@B*CJOJQJ^JaJmH	@phsH	@+hT&�B*CJOJQJ^JaJmH	@phsH	@eqrbg������38����6Eps&�Ƕ��������������t���fJ7h�gh�g5�B*CJOJQJ\�^JaJmH	@phI&msH	@h�K~CJOJPJQJaJ ht�h�O�CJOJPJQJaJht�CJOJPJQJaJh�O�CJOJPJQJaJ)h�O�ht�B*CJOJPJQJaJph� ht�ht�CJOJPJQJaJ7h5S�h�2�5�B*CJOJQJ\�^JaJmH	@phI&msH	@7h5S�h@@5�B*CJOJQJ\�^JaJmH	@phI&msH	@&'e�/01) ; ;#Z#�$�$�$�$�(�(���չ�չ՝ՌpWF� h�Gh�GCJOJPJQJaJ1h<�5�B*CJOJQJ\�^JaJmH	@phI&msH	@7h�VXh�VX5�B*CJOJQJ\�^JaJmH	@phI&msH	@ hW+�hW+�CJOJPJQJaJh�+�CJOJPJQJaJh�eCJOJPJQJaJh�GCJOJPJQJaJh�YCJOJPJQJaJ h�Yh�YCJOJPJQJaJ1h�V�5�B*CJOJQJ\�^JaJmH	@phI&msH	@�(�(�(�*�*�+�+x,y,	..�.�.�/�/22"2#2�ʹ����������}�oV=1h�S5�B*CJOJQJ\�^JaJmH	@phI&msH	@1h�05�B*CJOJQJ\�^JaJmH	@phI&msH	@h�VXCJOJPJQJaJ1h�}5�B*CJOJQJ\�^JaJmH	@phI&msH	@h�eCJOJPJQJaJ)h�eh�eB*CJOJPJQJaJph� h�eh�eCJOJPJQJaJ1h�e5�B*CJOJQJ\�^JaJmH	@phI&msH	@7h�eh�e5�B*CJOJQJ\�^JaJmH	@phI&msH	@2#2�2�2�3g45�5�6�7_8?9������`````9$d���$d����%d����&d����'d����(d����N���������O���������P���������Q���������R���������a$gdwt�9$d���$d����%d����&d����'d����(d����N���������O���������P���������Q���������R���������a$gd�k�$��d���7$8$H$]�^�a$gd�$��gd�$$d��xa$gd�S#2�2�2�2�2�2�2,3K3N3�3�3�3�3�3�3�3�3�3�3�3�3�3I4L4��§��n�YnYB�Y�Y�Y��n�n�,h�$h�$6�B*CJOJPJQJaJph)hwt�hwt�B*CJOJPJQJaJph)h�$h�$B*CJOJPJQJaJph#hwt�B*CJOJPJQJaJph#h�$B*CJOJPJQJaJph4h�Bh�2�B*CJOJQJ\�^JaJmH	@phsH	@7h5S�h@@5�B*CJOJQJ\�^JaJmH	@phI&msH	@ h�Sh��CJOJPJQJaJ h�0h�0CJOJPJQJaJL4W4j4�4�4�4�4�4�4�4�4555�5�5�5�5�5�������׫���p[D[/p)hwt�hwt�B*CJOJPJQJaJph,hkn�hkn�6�B*CJOJPJQJaJph)hkn�hkn�B*CJOJPJQJaJph#hwt�B*CJOJPJQJaJph)h��h��B*CJOJPJQJaJph&h��6�B*CJOJPJQJaJph,h��h��6�B*CJOJPJQJaJph)h�$h�$B*CJOJPJQJaJph#h�$B*CJOJPJQJaJph,h�Z�h�$6�B*CJOJPJQJaJph�50616�6�6�6�6�6�6�6�6�6�6�6	77`7c7u7v7�7�7���վ�լլ՚�s�s�\Hs�&h8g�6�B*CJOJPJQJaJph,h8g�h8g�6�B*CJOJPJQJaJph)h8g�h8g�B*CJOJPJQJaJph#h8g�B*CJOJPJQJaJph#hwt�B*CJOJPJQJaJph#h:�B*CJOJPJQJaJph,h:�h:�6�B*CJOJPJQJaJph)hwt�hwt�B*CJOJPJQJaJph)h:�h:�B*CJOJPJQJaJph�7�7�7�75888D8b8�8�89!909>9?9B9�9�9�9�9�9�9�9::::�����������n\n\En\n\n\,h�[�h�[�6�B*CJOJPJQJaJph#h�[�B*CJOJPJQJaJph)h�[�h�[�B*CJOJPJQJaJph,h�:h�:6�B*CJOJPJQJaJph#h�:B*CJOJPJQJaJph)h�:h�:B*CJOJPJQJaJph,hkn�hkn�6�B*CJOJPJQJaJph)hkn�hkn�B*CJOJPJQJaJph#hkn�B*CJOJPJQJaJph:::::::E:H:�:�:�:�:�:�:�:�:�:�:�:�:�:�:�:�:-;.;/;?;B;I;J;K;O;Q;S;X;�;�;<<<L<M<t<u<v<���������د��������������������������؝�����)h�aoh�aoB*CJOJPJQJaJph#h�aoB*CJOJPJQJaJph,h�[�h�[�6�B*CJOJPJQJaJph#h�:B*CJOJPJQJaJph#h�[�B*CJOJPJQJaJph)h�[�h�[�B*CJOJPJQJaJph.?9:�:T;<�<�=������$��d���7$8$H$]�^�a$gdK9$d���$d����%d����&d����'d����(d����N���������O���������P���������Q���������R���������a$gdwt�v<|<~<�<�<�<�<�<�<�<�<�<�<�����ԭ�uZB'4h��h��B*CJOJQJ\�^JaJmH	@phsH	@.h�n�B*CJOJQJ\�^JaJmH	@phsH	@4h�n�h�n�B*CJOJQJ\�^JaJmH	@phsH	@7h�Bh�S5�B*CJOJQJ\�^JaJmH	@phsH	@7h�Bh�Sc5�B*CJOJQJ\�^JaJmH	@phsH	@)hwt�h�[�B*CJOJPJQJaJph#h�aoB*CJOJPJQJaJph)h�aoh�aoB*CJOJPJQJaJph,h�aoh�ao6�B*CJOJPJQJaJph�<�<�=�=�=�=�=�=�=�=�=�=�=�=�ʯ�x��`H`-4h�Bh�2�B*CJOJQJ\�^JaJmH	@phsH	@.h�n�B*CJOJQJ\�^JaJmH	@phsH	@.h��B*CJOJQJ\�^JaJmH	@phsH	@7h��h�Z�6�B*CJOJQJ\�^JaJmH	@phsH	@4h�Bh�Z�B*CJOJQJ\�^JaJmH	@phsH	@4h�Bh];�B*CJOJQJ\�^JaJmH	@phsH	@4h�n�h�n�B*CJOJQJ\�^JaJmH	@phsH	@4h�Bh�ScB*CJOJQJ\�^JaJmH	@phsH	@
21�h:p�2���. ��A!��"��#��$��%�������b%���������666666666vvvvvvvvv66>6666666>6666666666666666666666�666666666�666666666686hH66666<6666666666>>6666666666666666666666666666666666666666666666>�666���� 0@P`p������6(66 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p��8X�V~PJ_HmH	nH	sH	tH	b`�b�2�Normal�9�9d]�9^�9$CJOJPJQJ_HaJmH	sH	tH	ll�2��	Heading 1$$��@&/5�B*CJOJPJQJ\�^JaJmH	ph6_�sH	dd�2��	Heading 2$$��@&'5�B*CJOJPJQJ\�^JaJphO��DA �D
Default Paragraph FontRi�R
0Table Normal�4�
l4�a�(k �(
0No ListR� �R�2�0Balloon Textd�CJOJPJQJaJtH6B6�2�	Body TextCJaJh"h�2�Captiond�]�^�a$,B*CJOJPJQJ\�^JaJmH	phsH	R "R�2�0Comment Textd�CJOJPJQJaJtH@j !"@ �2�0Comment Subject5�\�d^Bd�2�0Normal (Web)d��d�d[$\$CJOJPJQJ^JaJtHAB' �QB�2�0Comment ReferenceCJaJ.X �a.�2�@Emphasis6�]�6U �q6�2�0	Hyperlink>*B*ph�*W �*�2�`Strong5�\�J�/�J�2�0Comment Text CharCJaJmH	sH	V�/�V�2�0Balloon Text CharCJOJQJ^JaJmH	sH	`� �`�2� List Paragraph��]�^��m$CJPJaJmH	sH	tHR�/�R�2� List Paragraph CharOJQJ^JmH	sH	z��z�2�0sample-citationd��d�d[$\$]�^�$CJOJPJQJ^JaJmH	@sH	@tH	@|�/��|�2�
MDPI_3.1_text$��dG$H$`��a$,B*OJPJQJ_H	aJhmH	phsH	tH�����2�MDPI_2.1_heading1!d���x@&G$H$]�^�35�B*CJOJPJQJ^J_H	h�mH	phsH	tHV�/�V�2�0Comment Subject Char5�CJ\�aJmH	sH	f�/�f�2�Default!7$8$H$1B*CJOJPJQJ^J_HaJmH	@phsH	@tH	2�1"2�2�	lofigures"a$p�2p�2�loftable#$$dh���a$,B*CJOJPJQJ\�^JaJmH	phsH	,��A,�2�
aut_con_inPK!����[Content_Types].xml���j�0E����ж�r�(��΢Iw},��-j��4	��w�P�-t#bΙ{U�����T�U^h�d}㨫��)��*1P�'��	�^��W��0)��T�9<�l�#��$yi}��;�~@��(��H����u�*Dנz��/0�ǰ��$��X��3aZ����,�D0j~�3߶�b��~i>���3�\`�?�/�[���G��\�!�-�Rk.�s�Ի�..���a濭?��PK!�֧�6_rels/.rels���j�0���}Q��%v/��C/�}�(h"���O�
����=������ ����C?�h�v=��Ʌ��%[xp��{۵_�Pѣ<�1�H�0���O�R�Bd���JE�4b$��q_����6L�R�7`������0̞O��,�En7�Li�b��/�S���e��е�����PK!ky���theme/theme/themeManager.xml�M
� @�}�w��7c�(Eb�ˮ��C�AǠҟ����7��՛K
Y,�
�e�.���|,���H�,l����xɴ��I�sQ}#Ր���� ֵ+�!�,�^�$j=�GW��)�E�+&
8���PK!����Ptheme/theme/theme1.xml�YOo�6��w toc'vu�ر�-M�n�i���P�@�I}��úa��m�a[�إ�4�:lЯ�GR��X^�6؊�>$�������!)O�^�r�C$�y@�����/�yH*��񄴽)�޵��߻��UDb�`}"�qۋ�Jח���X^�)I`n�E���p)���li�V[]�1M<������O�P��6r�=���z�gb�Ig��u��S�eb��O������R�D۫����qu	�g��Z����o~ٺlAp�lx�pT0���+[}`j���zA��V�2�F���i�@�q�v�֬5\|��ʜ̭N��le�X�ds���jcs���7���f����
��W��+�Ն�7����`���g�Ș��J���j|��h(�K��D-����
dX��iJ�؇(��x$(��:��;�˹!�I_�T��S1�����?E��?�����?ZBΪm���U/������?�~����xY���'���y5�g&΋/����ɋ�>���G�M�Ge���D�����3Vq%'#q�����$�8��K�����)f�w9:ĵ��
x}r�x����w���r�:\TZaG�*�y8I�j�bR��c|XŻ�ǿ�I
u3KG�nD1�NIB�s���
��R��u���K>V�.EL+M2�#'�f��i~�V��vl�{u8��z��H�
�*���:�(W�☕
~��J�T�e\O*�tHG��HY��}KN�P�*ݾ˦���TѼ�9/#��A7�qZ��$*c?���qU��n��w�N��%��O��i�4=3ڗP��
����1�P�m\\9���������Mؓ�2a�D�]�;Yt�\��[x����]�}Wr��|�]��g-���
eW�
�)6-r��CS�j��
i�d	�DЇA�ΜIqbJ#x�꺃6k���#��A�Sh��&ʌt(Q�%��p%m��&]�caSl=�X�����\P�1�Mh�9�M��V�dDA��aV�B��[݈fJ�íP|8�քA�V^��f
�H��n���-��"�d>�z��n��NJ�	�ة�>�b���&����2��v����Kyϼ��D:����,AGm��\nz��i�Ù��.uχYC�6�OMf��3o�r��$��5�����NH�T[XF64�T,ќ���M0�E)`#�5�XY�`�פ;��%�1�U�٥m;���R>QD����D�cp�U�'��&LE�/p���m���%]�����8fi��r�S4�d7y\�`�J�n���ί�I�R��3U�~7+���׸#��m�q�BiD���������i*�L6�9�m�Y&���i���HE��=(K&�N!V�.K�e�LD�ĕ�{D	����vEꦚde��NƟ��e�(�MN9ߜR�6����&3(��a���/D��U�z�<�{ˊ�Y��ȳ����V���)�9�Z[��4^n��5���!J��?��Q�3�eBo�C����M����m<�.�vp�����IY�f���Z�Y_p�[�=al-�Y�}Nc͙���ŋ4vfa��vl����'S��A�8�|�*u�{��-�ߟ0%M0�7%����<���ҍ���PK!
ѐ��'theme/theme/_rels/themeManager.xml.rels��M
�0���wooӺ�&݈Э���5
6?$Q��
�,.�a��i����c2�1h�:�q��m��@RN��;d�`��o7�g�K(M&$R(.1�r'J��ЊT���8��V�"��AȻ�H�u}��|�$�b{��P����8�g/]�QAsم(����#��L�[������PK-!����[Content_Types].xmlPK-!�֧�6+_rels/.relsPK-!ky���theme/theme/themeManager.xmlPK-!����P�theme/theme/theme1.xmlPK-!
ѐ��'�	theme/theme/_rels/themeManager.xml.relsPK]�
<?xml version="1.0" encoding="UTF-8" standalone="yes"?>
<a:clrMap xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" bg1="lt1" tx1="dk1" bg2="lt2" tx2="dk2" accent1="accent1" accent2="accent2" accent3="accent3" accent4="accent4" accent5="accent5" accent6="accent6" hlink="hlink" folHlink="folHlink"/>�5j����_�	(F�)e&�(#2L4�5�7:v<�<�=!"#$&'()*+-./01342?9�= %,2�L�#����@�����������0�(	�
��B
�S����	?�>EFK����!(5<AI{
�
`l��fq��!g"k"�%�%�%�%�&�&�&�&J'P'�*+++++(+.+9+>+?+D+�+�+�+�+r,y,z,�,-
----#-%-+-5-;-�-�-�-�-�-�-1.7.n.|.�.�.�.�.�.�.�.�.�.�.�.�.�.�.�./�/�/�/�/�/�/�/�/�/�/:0>0?0D0j0t0u0z0|0�0�0�0�0�0�0�0�0�0�0�0!1$1'1,1O1U1V1_1w1|1�1�1�2�2135363?3X3_3b3h3p3w33�3�3�344%4*4�4�4�4�4�4�4�4�4�4�4M5Y5�5�5�5�5�5�
��57������GM�#�#�#�#�&�&g,�,�,�,W-Y-�/70_0�0G2�2�2�2�2.3L4u4�4�4�5333333333333333333333ZZ818191�4�4�4�4�5�5�5�5�5�Cp��Cp����������s���s������������Lm�2�������������W���^��`�W�o(.���\���^��`�\�OJ	QJ	o(l������^��`���.������^��`���.��p�L�^�p`�L�.��@���^�@`���.�����^�`���.����L�^��`�L�.������^��`���.������^��`���.��P�L�^�P`�L�.s����Cp��Lm����������������	@	@	@	@	@	@	@	@	@�4�8�)Wejsv�)W-��2g�T�rB�P(
K5D��e�v.{B2	�
@@\�NJZ� 
-'�%�r�}
[�hCq�~�G�Y�S�$�b-"gl�h,�fUD /F A#!�$�e$�y$�&%@%DK%�x%�V&O\&!n&�)bC)B
*�j+�6,�7-�s.u/ )/�0�s0MS2023Cg3�k3�4s^405>C5�L7
r8�:#?:M:Ve:�M;�I<�w<�=�R=�?j+?&#@�Bz
BjKC�vC�2D�
EzGReG�tL
+M*;N�=N�_N\<Q4R�EUzrW�VX�1Y)~^6`�H`�p`,xb�
c@6c�6c�Sc�"d4e[f�gc-gXKg�Xg�yjkuqlNmL/nob!o�ao%qMPq�pqbrtt�1t"6t>u:Tu�w&x&7y1z�1z�Az\z�F{|�K~9�5�wt�e9�<��_���_�p��c�HE�>T���e����<��4���U8��k��n�2r��E��[�2#�#2��%����1��`��t��"����2��f��y��%������b�^����3���V�y�7�tA���r%��Z�];��T�BW�Qz�+��Z��:��Q�ph��!�,(��v�ic�8g��s�2�y�V>��>�/R�5S�p}�b�g(�W�.�::����
���W+�B5�(7�7�aV�y� ��G��}L��V�kn�t6��H�>d�A���+7��O���ZW��9��V����Z�"8��}����`���:�\Y�.��#����G�P��8�,B��D��W��<�:s��|��"��;��0��_�bg�z�Q.�}z��t�WG�bs��%�1��[�c]����}�N�_��Y�&P��D�P��4�WO��\�M���KU�&h�#�T&��i�n�O!��V�>-���'P��v�_��=��#��9�t�%u����Z�Z��W� Q��Y�>d��K��k��n����k��C�[X�4t���{��K��r������+��A�>U��j��n;QF�S��n�Li�l�V(2u�|4Sv�p��;�a2�&pS�,]�8�8�.(��l/�.f_��q��F_	�=�	�Y�	�h
�Q�
�K�/^�'}�~,�`d��;/�HB
>�
�4�
8�
1%/�HV�
[���9&
:B�5%� rpP�k��TI�$f�*�;R��Xa�g�
o0��{�jo4�A+�r=1nC�d��'��'!�Y��\�pv��V��a�\8i �!#�VT�{���)&j�;���Bs>T��B5o3�]z�ff��-f�&||s�O� j@�!�M�!�"Y,"�J�"3i#&9?#U>R#��#k�#�
1$�
9$�G$G|~$g"�$�Z'%ClL%�Tt%�+�%�8�%�&<y'U`$'�0'�aw'�'�'�*�'�(e#)0t,)��)`*`y�*P)�*I(�*�E+e-?z	-��-��-�f.X,�.�E�.�:�.X/]
/M�/��/W0y0])�0YL�0�$�0LB1��1�2't2�3�b4_G4j�4A
50'S5W�5�&C6�_�6Vi@7�o�8�l9�R�9�(:PR�:=�:T~1<gH<��<��<`(�=;�=�0>�e�>�I�>h<�>�?t�?�Q�?�l�@y0�A#+B~D
Cx6VC3yC�uD�D��D�JE�$qE�=�E�_�F�_�F�K�G�b�GO4�GW;H<
�HY~I�}IhK�IUf�I!J"iJ�QK*ggKv�K"J2L��L��M�B�MyKN�VN�.|N�DOB�Oi�O�T#P�U�P�j�P�	Qgx�R��R�3SdS�NT�\]T:w�T�4V�'W�o?W�}eWEDiW�arWQ=�W��WlX�{X6?MXtJ�X�1�X��Y�w�Y�J�Y�qZ�>�ZuX�Z��Z0R[7g[�Ph[aV�[�[z\�|<\�oE\�3�\�I_]�_�]	vA^�7�^�u�_�{o`�Q�`gkbah�a3@b(I{b�6�bXM�b^l�b�cN;-c�%�dR9�d�+�e�T�el�e0[>f�:�f�R�f�Cg3Dg�_.gl6dg"&�g�bh8Z"hW�h�Bim;Li�$�i�q�i:Obj�@�j�N�j��j	k�%k|�k�o�kc9�m�)in�Z�n�	o�11oT?�p%_q�P|qiw�q�ir�y6suos>�s� �s�Sktwt�l�t�0Nu,ivur�udC�u]v	vF3)v�dUw
}w�q�w�p�w�]x�cgx�|�x�['y�"�y�h�yA�y~Azl@�ze{�w�{)t�{�m|�)/|d{�|�+8}�Hc},<�}�g~yr�~6A'�eF!��
��5�5�@�QQ`�JJQQ�5�@��Unknown������������G��.�Cx�	�Times New Roman5��Symbol3.��*�Cx�	�ArialA.���Arial Narrow;���(SimSun�[SO7.���@�Calibri7���@�Cambria5.��.�[`�)�TahomaK���@�Palatino Linotype;��WingdingsA���$B�Cambria Math"q���hz2�ǚ��g'��-�a�-a1�������20�5�5N�Q����HX	�$P�����������������������V�2!
xx���Shrishti PrakashSHALINI����Oh��+'��0`�������	��
(
4@HPX�Shrishti PrakashNormalSHALINI39Microsoft Office Word@��"@Mܺ;�@�c�����-����՜.��+,��D��՜.��+,��4�hp��������
���Microsofta�5Titled ?GKSOProductBuildVer�1033-11.2.0.9255	

 !"#$%&'()*+,-./012345����789:;<=����?@ABCDEFGHIJKLMNOPQRSTUVWXY����[\]^_`a����cdefghi��������lmn��������qr��������������������������������������������������������Root Entry��������	�FpAғ���p�Data
������������61Table��������>�6WordDocument
����4jSummaryInformation(������������ZDocumentSummaryInformation8��������bMsoDataStore��������𼳓����Γ���5X�X�V���UCRPD�UH�V5��==2����
𼳓���0Rʓ���Item
����	����Properties������������F�HUBLX�4S�0DXIE���4�0�==2��������𼳓����Γ���Item
��������
�Properties������������UCompObj����y����������������������������	����
����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������<?xml version="1.0" encoding="UTF-8" standalone="yes"?><s:customData xmlns="http://www.wps.cn/officeDocument/2013/wpsCustomData" xmlns:s="http://www.wps.cn/officeDocument/2013/wpsCustomData"><customSectProps><customSectPr/></customSectProps></s:customData><?xml version="1.0" encoding="UTF-8" standalone="no"?>
<ds:datastoreItem ds:itemID="{B1977F7D-205B-4081-913C-38D41E755F92}" xmlns:ds="http://schemas.openxmlformats.org/officeDocument/2006/customXml"><ds:schemaRefs><ds:schemaRef ds:uri="http://www.wps.cn/officeDocument/2013/wpsCustomData"/></ds:schemaRefs></ds:datastoreItem><b:Sources SelectedStyle="\APA.XSL" StyleName="APA" xmlns:b="http://schemas.openxmlformats.org/officeDocument/2006/bibliography" xmlns="http://schemas.openxmlformats.org/officeDocument/2006/bibliography"></b:Sources><?xml version="1.0" encoding="UTF-8" standalone="no"?>
<ds:datastoreItem ds:itemID="{2D017598-9E79-464B-835C-8139DF47BB6B}" xmlns:ds="http://schemas.openxmlformats.org/officeDocument/2006/customXml"><ds:schemaRefs><ds:schemaRef ds:uri="http://schemas.openxmlformats.org/officeDocument/2006/bibliography"/></ds:schemaRefs></ds:datastoreItem>��
����	�F'Microsoft Office Word 97-2003 Document
MSWordDocWord.Document.8�9�q

Youez - 2016 - github.com/yon3zu
LinuXploit