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Plasmin Delivered with Ultrasound Bubble-Busting Technology More Effective Busting Clots Than TPA

By MedImaging International staff writers
Posted on 04 Jun 2013

A new study has revealed that when delivered with the use of ultrasound, the natural enzyme plasmin is more effective at dissolving stroke-causing blood thromboses than the current standard of care, recombinant tissue plasminogen-activator (rt-PA).

The innovative delivery technique involved snaring plasmin into bubble-like liposomes, delivering them to the clot intravenously and bursting it via ultrasound. That technique is necessary, according to University of Cincinnati (UC) College of Medicine (OH, USA) associate professor of emergency medicine George Shaw III, MD, PhD, because plasmin cannot be delivered through conventional techniques. Intravenous (IV) delivery of rt-PA is designed to resolve that hurdle by catalyzing the conversion of existing plasminogen inside the body to plasmin, which then degrades blood clots.

“Plasmin is the enzyme that actually chews up the fibrin in clots,” said Dr. Shaw. “The problem is you can only give plasmin interarterially, which has safety risks and takes longer to deliver. IV therapy is always easier and quicker, but if you give plasmin intravenously, the body inhibits it immediately. If you can encapsulate it, it doesn’t get inhibited and you can target it to the clot.”

Dr. Shaw and researchers Madhuvathi Kandadai, PhD, and Jason Meunier, PhD, in their in vitro study, enclosed plasmin and a gas bubble inside a liposome. They then delivered the liposome to a clot in an in-vitro lab clot model and dissolved it using ultrasound waves, thereby delivering the plasmin enzyme to the clot. Thromboses treated with plasmin, after 30 minutes, demonstrated considerably greater degradation than clots treated with rt-PA. They worked with colleague Christy Holland, PhD, professor in UC’s cardiovascular diseases division, to develop the technique. As director of the Image-guided Ultrasound Therapeutics Laboratories at UC, Holland has evaluated the use of liposomes and ultrasound to deliver drugs in a less invasive, more targeted manner.

The standard of care for acute ischemic stroke is intravenous (IV) delivery of US Food and Drug Administration (FDA)-approved rt-PA within three hours of stroke onset. Ischemic stroke is the most typical type of stroke, accounting for approximately 87% of all strokes.

However, Dr. Shaw noted that there is a critical need for a safer and more effective thrombolytic, as rt-PA carries a risk of hemorrhaging. Intracranial hemorrhage currently occurs in 6% of patients receiving rt-PA therapy. “Previous in vivo studies have demonstrated better safety of plasmin as compared with rt-PA,” he said. “Currently, intra-arterial plasmin is undergoing clinical trials. Our next step is to work on targeting the liposome by putting antibodies on its surface that will stick it to the clot. We also want to improve the efficiency of encapsulating the plasmin in the liposome. Right now, about 15% of the plasmin gets into the liposome—we’re aiming for 50%.”

Dr. Kandadai, a postdoctoral fellow in the UC department of emergency medicine, presented their findings at the Society for Academic Emergency Medicine annual meeting, held May 14-18, 2013, in Atlanta (GA, USA). Dr. Meunier, a research assistant professor of emergency medicine, is also a coauthor.

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58 (455.85632324219): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

59 (!!!!! 12249.946594238): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

60 (802.04010009766): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

61 (77.009201049805): select cover from jos_number where journalid in (5) and cover is not null order by left(issue,2)+right(issue,2)*12 desc limit 1

62 (556.94580078125): SELECT fid FROM jos_deeppockets WHERE id=294746587 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294746587 AND published='1' LIMIT 1

63 (56.028366088867): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=214 ORDER BY `ordering`

64 (849.96223449707): select jos_twitters.link from jos_twitters where cat=10

65 (72.002410888672): select jos_facebook.link from jos_facebook where cat=10

66 (43.153762817383): select jos_google_plus.link from jos_google_plus where cat=10

67 (!!!!! 6395.1015472412): select jos_linkedin.link from jos_linkedin where cat=10

68 (60.081481933594): SELECT fid FROM jos_deeppockets WHERE id=294746587 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294746587 AND published='1' LIMIT 1

69 (45.061111450195): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=214 ORDER BY `ordering`

70 (792.9801940918): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294746587 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (440.12069702148): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294746587 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (53.882598876953): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

73 (!!!!! 3345.0126647949): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (101.80473327637): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (37.908554077148): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (!!!!! 2786.8747711182): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294746587 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (585.79444885254): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294746587 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (226.97448730469): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

90 (!!!!! 1857.9959869385): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (699.99694824219): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (!!!!! 2521.0380554199): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (!!!!! 1331.090927124): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (59.127807617188): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (38.14697265625): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (!!!!! 6021.0227966309): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (!!!!! 4743.0992126465): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (758.88633728027): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (79.154968261719): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (!!!!! 2018.928527832): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

105 (333.07075500488): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

106 (869.0357208252): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294746587 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (!!!!! 1247.8828430176): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294746587 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (!!!!! 1780.9867858887): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

109 (186.92016601562): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

110 (293.01643371582): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294746587 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (586.98654174805): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294746587 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (!!!!! 1327.0378112793): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

113 (!!!!! 1219.9878692627): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

114 (!!!!! 1787.1856689453): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

115 (611.0668182373): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

116 (!!!!! 1845.8366394043): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

117 (279.90341186523): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

118 (942.94548034668): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

119 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

120 (!!!!! 3251.0757446289): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

121 (293.97010803223): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

122 (656.8431854248): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 64997.911453247): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7

124 (!!!!! 5275.0110626221): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294746587 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294746587 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 14528.036117554): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

126 (!!!!! 4976.0341644287): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

127 (57.93571472168): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

128 (43.153762817383): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

129 (302.07633972168): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

130 (194.07272338867): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

131 (661.84997558594): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

132 (50.783157348633): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

133 (!!!!! 1061.9163513184): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

134 (48.87580871582): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

135 (494.00329589844): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (328.06396484375): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (51.975250244141): SELECT name FROM jos_deeppockets WHERE id=214

138 (40.054321289062): SELECT name FROM jos_deeppockets WHERE id=214

139 (769.13833618164): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))214((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (!!!!! 1508.9511871338): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))214((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (457.0484161377): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

142 (74.148178100586): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

143 (!!!!! 16011.953353882): TRUNCATE TABLE jos_trademed_module

144 (!!!!! 5499.1245269775): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294746587 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (!!!!! 1789.0930175781): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294746587 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (!!!!! 3248.929977417): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (89.883804321289): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (!!!!! 1720.9053039551): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

149 (410.79521179199): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

150 (!!!!! 10844.945907593): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6

151 (93.936920166016): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

152 (64.849853515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

153 (!!!!! 2001.0471343994): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294746587 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294746587 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (78.916549682617): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=214 or channel_id is null)

155 (39.100646972656): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=214 or channel_id is null)

156 (!!!!! 3677.8450012207): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (122.0703125): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

158 (61.988830566406): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294746587 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294746587 AND published='1' LIMIT 1

159 (286.10229492188): select jos_twitters.link from jos_twitters where cat=10

160 (!!!!! 3320.9323883057): select jos_facebook.link from jos_facebook where cat=10

161 (80.108642578125): select jos_google_plus.link from jos_google_plus where cat=10

162 (38.14697265625): select jos_linkedin.link from jos_linkedin where cat=10

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