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Philips and Glygenix Therapeutics to Develop Ultrasound-Mediated Gene Therapy

By MedImaging International staff writers
Posted on 21 Aug 2009

Philips Healthcare (Best, The Netherlands) and GlyGenix Therapeutics, Inc. (Woodbridge, CT, USA) announced a joint research agreement to research the feasibility of using ultrasound technologies for gene therapy. In particular, the collaboration will explore the treatment of glycogen storage disease-type 1a (GSD-1a) in preclinical studies.

The collaboration unites Philips' expertise in medical imaging technologies for diagnosis and minimally invasive medical procedures with GlyGenix's expertise in correcting the genetic defect in GSD-1a. "The potential to deliver genes using a targeted approach will be a significant advance for correcting genetic defects and could offer the prospect of curing hereditary diseases such as GSD-1a,” commented William Fodor, CSO of GlyGenix Therapeutics. "Philips' ultrasound-mediated DNA delivery techniques offer the opportunity to deliver genes without the size constraints and limitations of viral packaging systems, and thus open the door to the development of more robust and effective therapeutic genes.”

"Medical imaging systems already play a crucial role in minimally-invasive medical procedures such as opening obstructed arteries, correcting heart rhythm disorders, or sampling tissue biopsies of suspected lesions,” said Henk van Houten, senior vice president of Philips Research and head of the healthcare research program. "The development of ultrasound techniques that could noninvasively target the delivery of drugs, genes, and stem cells to specific parts of the body opens up further possibilities to advance patient care.”

GSD-1a is an inherited disease that makes it impossible for the body to regulate blood sugar (glucose) levels, due to a defective G6Pase gene that prevents the body from producing an enzyme called glucose-6-phosphatase. Although it is a rare disease, only affecting approximately 1 in every 100,000-200,000 births in the United States alone, it results in a significant reduction in patients' quality of life and can lead to potentially life-threatening comorbidities in early adulthood. Currently, there are no approved curative treatments for GSD-1a. Correcting the genetic defect that causes it could offer the prospect of an effective therapy that would allow patients with GSD-1a to lead a normal life.

Current gene therapies that rely solely on the bloodstream to deliver corrective gene molecules typically fail to deliver sufficient quantities to the target organs. However, by directing focused ultrasound to target organs following DNA delivery, an increase in uptake via a process known as sonoporation has been successfully demonstrated in pre-clinical studies. Sonoporation increases the permeability of cell walls to allow the uptake of large molecules, thereby enabling the delivery of therapeutic genes.

Compared to current gene therapies that use viral vectors to infect cells, this ultrasound-mediated technique carries no risk of an antiviral immune or inflammatory response. In addition, this targeted approach could reduce side effects.

The proposed treatment is known as ultrasound-mediated plasmid DNA (pDNA) delivery. The research program into it will specifically target the expression of a functional human G6Pase therapeutic pDNA to the liver, the primary organ responsible for glycogen storage and glucose release. Preclinical studies to investigate the feasibility of the technique will be performed by Philips Research and GlyGenix Therapeutics in collaboration with the Duke University School of Medicine's division of medical genetics (Durham, NC, USA), a recognized leader in GSD-1a diagnosis, managed care, pediatric genetics, and experimental models.

GlyGenix Therapeutics holds a worldwide exclusive license to the G6Pase gene, protein, and related mutations for the treatment of GSD-1a. GlyGenix will seek to obtain orphan drug designation for the treatment of GSD-1a, which would provide seven years of market exclusivity.

GlyGenix Therapeutics is a privately held biotech company developing therapeutic solutions for severe metabolic disorders. The company's initial focus is in using gene therapy products with nonviral delivery systems for the treatment of GSD1a, a rare and severe chronic genetic liver disease for which no approved therapies exist. With the aid of a sizable body of preclinical data, GlyGenix Therapeutics, Inc is poised to expedite the initiation of clinical trials for the treatment of GSD1a.

Related Links:
Philips Healthcare
GlyGenix Therapeutics

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58 (!!!!! 4981.9946289062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

59 (!!!!! 2135.0383758545): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

60 (946.99859619141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

61 (!!!!! 2051.830291748): 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 (655.8895111084): SELECT fid FROM jos_deeppockets WHERE id=294725106 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294725106 AND published='1' LIMIT 1

63 (!!!!! 2161.979675293): 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=217 ORDER BY `ordering`

64 (82.015991210938): select jos_twitters.link from jos_twitters where cat=10

65 (44.107437133789): select jos_facebook.link from jos_facebook where cat=10

66 (46.014785766602): select jos_google_plus.link from jos_google_plus where cat=10

67 (38.862228393555): select jos_linkedin.link from jos_linkedin where cat=10

68 (70.810317993164): SELECT fid FROM jos_deeppockets WHERE id=294725106 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294725106 AND published='1' LIMIT 1

69 (84.877014160156): 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=217 ORDER BY `ordering`

70 (331.16340637207): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294725106 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (293.01643371582): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294725106 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (78.916549682617): 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 (!!!!! 2913.9518737793): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (723.12355041504): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (!!!!! 1095.0565338135): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (58.889389038086): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (85.830688476562): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (43.869018554688): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (44.822692871094): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (38.862228393555): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (95.129013061523): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294725106 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (46.014785766602): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294725106 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (49.114227294922): 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 (257.96890258789): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (394.82116699219): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (169.99244689941): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (108.00361633301): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (69.141387939453): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (211.95411682129): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (518.0835723877): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (!!!!! 1605.9875488281): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (!!!!! 1193.0465698242): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (179.05235290527): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (135.89859008789): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (118.01719665527): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (!!!!! 1950.9792327881): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

105 (293.01643371582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

106 (329.01763916016): 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=294725106 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (!!!!! 1444.1013336182): 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=294725106 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (!!!!! 1759.0522766113): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

109 (640.869140625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

110 (!!!!! 1996.0403442383): 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=294725106 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (!!!!! 1173.9730834961): 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=294725106 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (760.79368591309): 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 (419.85511779785): 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 (267.02880859375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

115 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

116 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

117 (39.100646972656): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

118 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

119 (40.054321289062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

120 (56.982040405273): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

121 (38.862228393555): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

122 (274.8966217041): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 75652.122497559): 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 (!!!!! 12191.0572052): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294725106 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294725106 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 57313.919067383): ( 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 (!!!!! 13987.064361572): ( 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 (!!!!! 3733.8733673096): 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 (!!!!! 4023.0751037598): 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 (529.05082702637): 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 (423.90823364258): 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 (376.93977355957): 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 (!!!!! 6253.0040740967): 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 (!!!!! 3918.8861846924): 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 (466.10832214355): 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 (!!!!! 4329.9198150635): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (!!!!! 4768.8484191895): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (!!!!! 3833.0554962158): SELECT name FROM jos_deeppockets WHERE id=217

138 (!!!!! 1181.1256408691): SELECT name FROM jos_deeppockets WHERE id=217

139 (854.0153503418): 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 '((;)|(^))217((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (472.06878662109): 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 '((;)|(^))217((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (!!!!! 1301.0501861572): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

142 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

143 (!!!!! 47657.012939453): TRUNCATE TABLE jos_trademed_module

144 (669.95620727539): 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=294725106 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (!!!!! 1561.164855957): 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=294725106 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (!!!!! 11196.851730347): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (!!!!! 7611.0363006592): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (324.96452331543): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

149 (293.01643371582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

150 (!!!!! 1389.9803161621): 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 (!!!!! 1636.0282897949): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

152 (!!!!! 1344.9192047119): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

153 (380.03921508789): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294725106 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294725106 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (406.98051452637): 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=217 or channel_id is null)

155 (!!!!! 6331.9206237793): 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=217 or channel_id is null)

156 (!!!!! 2304.0771484375): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (!!!!! 6669.9981689453): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

158 (941.99180603027): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294725106 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294725106 AND published='1' LIMIT 1

159 (!!!!! 7868.0515289307): select jos_twitters.link from jos_twitters where cat=10

160 (!!!!! 6840.9442901611): select jos_facebook.link from jos_facebook where cat=10

161 (!!!!! 6506.9198608398): select jos_google_plus.link from jos_google_plus where cat=10

162 (!!!!! 1148.9391326904): select jos_linkedin.link from jos_linkedin where cat=10

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