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MRI Probe Combined with Magnetic Nanostructure and Antibody can Detect Alzheimer’s Disease Early

By MedImaging International staff writers
Posted on 11 Jan 2015

Image: Amyloid beta oligomers bind to neurons and are distinct from amyloid plaques. Brain sections from an aged Alzheimer’s mouse model were probed with antibodies against Abeta oligomers (568-NU4, red) and amyloid plaques (ThioS, green). Images demonstrate that Abeta oligomers (568-NU4) are often associated with, yet distinct from, amyloid plaques (ThioS). Where both amlyoid plaques (green) and A-beta oligomers (red) overlap, shows up as yellow. NU4 labelling is more abundant than the ThioS staining. Data supports the notion that NU4 thus affords an excellent targeting antibody for the development of an amyloid beta oligomer-specific MRI probe that is distinct from currently available plaque probes (Photo courtesy of an adaption from Viola et al, Nature Nanotechnology, 2014).

A noninvasive magnetic resonance imaging (MRI) application has been designed that can detect the Alzheimer’s disease (AD) in a living animal, well before typical Alzheimer’s symptoms appear. The researchers created an MRI probe that combines a magnetic nanostructure with an antibody that searches for the amyloid beta brain toxins responsible for onset of the disease. The accumulated toxins, because of the associated magnetic nanostructures, are revealed as dark areas in MRI scans of the brain.

The interdisciplinary team of Northwestern University (Evanston, IL, USA) scientists and engineers developed the noninvasive MRI approach that can detect the disease in a living animal, and can do so at the earliest stages of AD, well before typical symptoms appear.

The research was led by neuroscientist William L. Klein, a professor of neurobiology in the Weinberg College of Arts and Sciences and materials scientist Vinayak P. Dravid, a professor of materials science and engineering at the McCormick School of Engineering and Applied Science, the researchers developed the MRI probe that pairs a magnetic nanostructure (MNS). This capability to identify the molecular toxins may one day enable scientists to both identify problems early and better design drugs or therapies to fight and track the disease. Furthermore, while not the focus of the study, early evidence suggests the MRI probe improves memory, too, by binding to the toxins to render them “tied up” to do additional damage.

“We have a new brain imaging method that can detect the toxin that leads to Alzheimer’s disease,” said Prof. Klein, who first identified the amyloid beta oligomer in 1998. “Using MRI, we can see the toxins attached to neurons in the brain,” Prof. Klein commented. “We expect to use this tool to detect this disease early and to help identify drugs that can effectively eliminate the toxin and improve health.”

With the successful demonstration of the MRI probe, Northwestern researchers now have established the molecular basis for the cause, detection by noninvasive MR imaging and treatment of AD. Dr. Dravid introduced this magnetic nanostructure MRI contrast enhancement approach for Alzheimer's following his earlier work utilizing MNS as smart nanotechnology carriers for targeted cancer diagnostics and therapy. (A MNS is typically 10–15 nm in diameter.)

The study’s findings were published online December 22, 2014, in the journal Nature Nanotechnology. This new MRI probe technology is identifying something different from conventional technology: toxic amyloid beta oligomers instead of plaques, which occur at a stage of AD when therapeutic intervention would be very late. Amyloid beta oligomers now are widely believed to be the cause in the onset of AD and subsequent memory loss.

The mobile amyloid beta oligomers, in a disease brain, attack the synapses of neurons, destroying memory and ultimately resulting in neuron death. As time progresses, the amyloid beta accumulates and starts to adhere together, forming the amyloid plaques that current probes target. Oligomers may appear more than 10 years before plaques are detected. “Noninvasive imaging by MRI of amyloid beta oligomers is a giant step forward towards diagnosis of this debilitating disease in its earliest form,” said Prof. Dravid.

There is a great need for what the Northwestern research team is doing—identifying and detecting the correct biomarker for new drug discovery. In spite of extraordinary efforts, no effective drugs exist yet for Alzheimer’s disease. “This MRI method could be used to determine how well a new drug is working,” Prof. Dravid said. “If a drug is effective, you would expect the amyloid beta signal to go down.”

The nontoxic MRI probe was delivered intranasally to mouse models with AD and control animals without the disease. In animals with Alzheimer’s, the toxins’ presence can be seen clearly in the hippocampus in MRI scans of the brain. No dark areas, however, were seen in the hippocampus of the control group.

The ability to detect amyloid beta oligomers, according to Prof. Klein, is significant for two reasons: amyloid beta oligomers are the toxins that damage neurons, and the oligomers are the first indication of trouble in the disease process, appearing before any other pathology. Moreover, the investigators observed that the behavior of animals with AD improved even after receiving a single dose of the MRI probe. “While preliminary, the data suggests the probe could be used not only as a diagnostic tool but also as a therapeutic,” said Kirsten L. Viola, a co-first author of the study and a research manager in Prof. Klein’s laboratory.

Along with the studies in live animals, the researchers also examined human brain tissue from Northwestern’s Cognitive Neurology and Alzheimer’s Disease Center. The samples were from individuals who died from AD and those who did not have the disease. After introducing the MRI probe, the researchers observed large dark areas in the Alzheimer brains, indicating the presence of amyloid beta oligomers.

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55 (82.969665527344): 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=294756617 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

56 (663.04206848145): 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=294756617 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

57 (!!!!! 1385.9272003174): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

58 (64.849853515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

59 (135.89859008789): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

60 (70.810317993164): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

61 (142.09747314453): 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 (624.17984008789): SELECT fid FROM jos_deeppockets WHERE id=294756617 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294756617 AND published='1' LIMIT 1

63 (301.83792114258): 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=212 ORDER BY `ordering`

64 (53.167343139648): select jos_twitters.link from jos_twitters where cat=10

65 (30.040740966797): select jos_facebook.link from jos_facebook where cat=10

66 (30.994415283203): select jos_google_plus.link from jos_google_plus where cat=10

67 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10

68 (31.948089599609): SELECT fid FROM jos_deeppockets WHERE id=294756617 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294756617 AND published='1' LIMIT 1

69 (30.994415283203): 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=212 ORDER BY `ordering`

70 (282.04917907715): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294756617 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (284.91020202637): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294756617 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (46.014785766602): 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 (52.928924560547): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (44.822692871094): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (45.061111450195): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (70.095062255859): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294756617 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (41.961669921875): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294756617 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (46.014785766602): 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 (68.902969360352): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (75.101852416992): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (45.061111450195): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (37.193298339844): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (34.809112548828): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (119.92454528809): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

105 (87.02278137207): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

106 (53.882598876953): 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=294756617 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (53.882598876953): 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=294756617 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (107.0499420166): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

109 (71.76399230957): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

110 (49.114227294922): 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=294756617 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (627.04086303711): 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=294756617 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (786.06605529785): 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 (442.9817199707): 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 (144.00482177734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

115 (77.962875366211): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

116 (101.08947753906): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

117 (53.882598876953): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

118 (63.896179199219): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

119 (43.869018554688): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

120 (52.213668823242): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

121 (40.054321289062): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

122 (450.13427734375): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 24858.951568604): 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 (589.13230895996): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294756617 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294756617 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 8505.10597229): ( 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 (82.015991210938): ( 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 (71.048736572266): 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 (47.922134399414): 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 (82.969665527344): 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 (43.153762817383): 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 (423.19297790527): 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 (46.014785766602): 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 (36.001205444336): 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 (30.994415283203): 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 (656.1279296875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (540.01808166504): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (334.9781036377): SELECT name FROM jos_deeppockets WHERE id=212

138 (51.021575927734): SELECT name FROM jos_deeppockets WHERE id=212

139 (819.92149353027): 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 '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (784.87396240234): 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 '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (159.97886657715): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

142 (76.055526733398): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

143 (!!!!! 10399.103164673): TRUNCATE TABLE jos_trademed_module

144 (195.02639770508): 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=294756617 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (92.983245849609): 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=294756617 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (603.91426086426): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (77.009201049805): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (104.90417480469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

149 (51.975250244141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

150 (!!!!! 1576.9004821777): 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 (113.01040649414): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

152 (77.962875366211): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

153 (63.896179199219): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294756617 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294756617 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (49.114227294922): 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=212 or channel_id is null)

155 (41.007995605469): 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=212 or channel_id is null)

156 (56.028366088867): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (151.15737915039): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

158 (53.882598876953): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294756617 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294756617 AND published='1' LIMIT 1

159 (40.054321289062): select jos_twitters.link from jos_twitters where cat=10

160 (41.961669921875): select jos_facebook.link from jos_facebook where cat=10

161 (40.054321289062): select jos_google_plus.link from jos_google_plus where cat=10

162 (77.962875366211): select jos_linkedin.link from jos_linkedin where cat=10

163 (365.01884460449): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

164 (!!!!! 1289.1292572021): insert into jos_banners_delta values (14615,'2025-06-23 08:57:56','216.73.216.120','view'),(14202,'2025-06-23 08:57:56','216.73.216.120','view'),(14203,'2025-06-23 08:57:56','216.73.216.120','view')

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