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Short Ultrasound Pulses Used to Reach Neurons Through Blood-Brain Barrier

By MedImaging International staff writers
Posted on 05 Oct 2011

A new ultrasound technique offers safe and noninvasive drug delivery to the brain regions affected by diseases such as Alzheimer’s, Parkinson’s, and epilepsy.

Engineers from Columbia University’s Fu Foundation School of Engineering and Applied Science (New York, NY, USA) have developed a new technique to reach neurons through the blood-brain barrier (BBB) and deliver drugs safely and noninvasively.

Up until now, scientists have thought that long ultrasound pulses, which can inflict collateral damage, were required. But in this new study, the Columbia Engineering team demonstrated that very short pulses of ultrasound waves can open the BBB--with the added benefits of safety and uniform molecular delivery--and that the molecule injected systemically could reach and target the targeted neurons noninvasively.

The study, led by Dr. Elisa Konofagou, associate professor of biomedical engineering and radiology, was published in the journal Proceedings of the [US] National Academy of Sciences the week of September 19, 2011. “This is a great step forward,” said Dr. Konofagou. “Devastating diseases such as Alzheimer’s and Parkinson’s that affect millions of people are currently severely undertreated. We hope our new research will open new avenues in helping eradicate them.”

Highly specific delivery of drugs to human organs is crucial for the effective treatment of many disorders. But the brain presents a difficult hurdle: it has a unique vascular system--the BBB--that acts as a closed door to prevent the entry of foreign molecules. While it protects the brain from potentially toxic substances, it also prevents the delivery of therapeutic drugs to the brain. Because many molecules cannot cross the BBB, available treatments for patients with neurologic disorders have been severely limited. Dr. Konofagou and her team are focused on getting the door opened enough to safely reach those cells that need to be treated.

Dr. Konofagou and her team have designed a focused ultrasound method that can target only the area of the hippocampus that is affected in early Alzheimer’s. In this study, they administered microbubbles to enhance the intended mechanical effect, and a high-field magnetic resonance imaging (MRI) to detect and map the area of BBB opening as well as quantify the permeability of the opened BBB. They also used fluorescence confocal microscopy to visualize the molecular diffusion and neuronal enhancement in three-dimensions (3D) to identify both highlighted neurons and their network.

More testing is planned with therapeutic drug treatments. The investigators have shown that therapeutic molecules initiate downstream effects after diffusion through the blood-brain barrier, starting with the cell membrane and all the way through the nucleus. They also are revealing the mechanism of the opening that involves stable oscillation or collapse of the bubble, with the former being the preferred mechanism because it is completely controlled by the pressure and microbubble size.

The BBB has been shown to recover within the range of three hours to three days depending on the aforementioned parameters used. Dr. Konofagou’s group has also recently reported that transcranial human targeting of the hippocampus, caudate, and putamen in the human brain is possible in both simulations and in vitro experiments, thereby paving the way towards clinical applications.

Related Links:
Columbia University’s Fu Foundation School of Engineering and Applied Science

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58 (587.94021606445): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

59 (!!!!! 8147.0012664795): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

60 (!!!!! 7916.9273376465): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

61 (!!!!! 6503.1051635742): 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 (!!!!! 1251.9359588623): SELECT fid FROM jos_deeppockets WHERE id=294737428 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294737428 AND published='1' LIMIT 1

63 (984.90715026855): 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 (604.86793518066): select jos_twitters.link from jos_twitters where cat=10

65 (71.048736572266): select jos_facebook.link from jos_facebook where cat=10

66 (!!!!! 2046.1082458496): select jos_google_plus.link from jos_google_plus where cat=10

67 (437.97492980957): select jos_linkedin.link from jos_linkedin where cat=10

68 (277.99606323242): SELECT fid FROM jos_deeppockets WHERE id=294737428 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294737428 AND published='1' LIMIT 1

69 (55.789947509766): 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 (904.08325195312): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294737428 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (394.82116699219): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294737428 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (270.84350585938): 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 (456.80999755859): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (152.1110534668): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (399.11270141602): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (!!!!! 3391.9811248779): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (490.90385437012): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (61.988830566406): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (!!!!! 3236.0553741455): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (154.01840209961): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (367.87986755371): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (159.97886657715): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (439.16702270508): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (54.836273193359): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (66.041946411133): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (46.014785766602): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (!!!!! 1400.9475708008): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294737428 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (545.97854614258): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294737428 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (298.02322387695): 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 (!!!!! 4995.1076507568): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (!!!!! 4800.0812530518): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (288.00964355469): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (54.836273193359): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (308.03680419922): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (51.021575927734): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (638.00811767578): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (61.988830566406): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (57.93571472168): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (79.870223999023): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (48.87580871582): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (421.04721069336): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (!!!!! 2188.9209747314): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (!!!!! 3304.9583435059): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

105 (!!!!! 1686.0961914062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

106 (133.99124145508): 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=294737428 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (826.12037658691): 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=294737428 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (199.0795135498): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

109 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

110 (119.92454528809): 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=294737428 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (!!!!! 3352.165222168): 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=294737428 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (916.95785522461): 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 (583.17184448242): 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 (175.95291137695): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

115 (92.029571533203): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

116 (661.13471984863): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

117 (322.10350036621): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

118 (821.82884216309): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

119 (177.14500427246): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

120 (190.97328186035): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

121 (263.92936706543): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

122 (735.04447937012): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 56818.008422852): 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 (!!!!! 3715.0382995605): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294737428 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294737428 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 18511.056900024): ( 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 (!!!!! 2948.9994049072): ( 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 (80.108642578125): 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 (52.928924560547): 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 (287.05596923828): 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 (156.87942504883): 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 (!!!!! 1168.966293335): 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 (79.154968261719): 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 (66.995620727539): 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 (46.014785766602): 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 (777.00614929199): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (!!!!! 2012.0143890381): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (784.15870666504): SELECT name FROM jos_deeppockets WHERE id=214

138 (71.048736572266): SELECT name FROM jos_deeppockets WHERE id=214

139 (!!!!! 1584.0530395508): 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 (870.94306945801): 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 (!!!!! 3777.027130127): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

142 (131.13021850586): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

143 (!!!!! 25931.119918823): TRUNCATE TABLE jos_trademed_module

144 (!!!!! 3583.9080810547): 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=294737428 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (102.04315185547): 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=294737428 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (927.92510986328): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (604.86793518066): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (!!!!! 4794.1207885742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

149 (250.10108947754): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

150 (!!!!! 3046.0357666016): 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 (!!!!! 1158.9527130127): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

152 (75.817108154297): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

153 (!!!!! 1454.8301696777): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294737428 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294737428 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (!!!!! 1096.0102081299): 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 (46.014785766602): 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 (37.908554077148): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (612.02049255371): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

158 (138.99803161621): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294737428 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294737428 AND published='1' LIMIT 1

159 (!!!!! 1466.0358428955): select jos_twitters.link from jos_twitters where cat=10

160 (!!!!! 5342.960357666): select jos_facebook.link from jos_facebook where cat=10

161 (617.98095703125): select jos_google_plus.link from jos_google_plus where cat=10

162 (92.029571533203): select jos_linkedin.link from jos_linkedin where cat=10

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