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Photoacoustic Imaging Could Monitor Prostate Cancer

By MedImaging International staff writers
Posted on 28 Jul 2016

Image: Cancer cells expressing PSMA (Photo courtesy Kent Nastiuk / RPCI).

A new study suggests that photoacoustic imaging (PAI) may be an effective tool for non-invasive monitoring of prostate cancer (PC).

Researchers at Roswell Park Cancer Institute (RPCI; Buffalo, NY, USA), the University of Rochester (NY, USA), and the Rochester Institute of Technology (RIT; NY, USA) conducted a study that focused laser light on phantoms containing PC cells, and then used ultrasound technology to see how molecular imaging agents that target the prostate-specific membrane antigen (PSMA) expressed under PAI. The two PSMA-targeting agents, ribonucleic acid aptamer (A10-3.2), and a urea-based peptidomimetic inhibitor (YC-27), were linked to the near-infrared (NIR) dye IRDye800CW.

The researchers found that the PAI with an acoustic lens enabled good discrimination between cells with and without the PSMA-targeting agent attached with both imaging agents. They found however, that YC-27 fluoresced much brighter and that conjugation of the modified chromophores was more tractable. They concluded therefore that the urea-targeting agent represents a better approach to developing “louder” signals necessary to overcome the challenges of detecting PC by PAI in vivo. The study was published in the June 2016 issue of the Journal of Biomedical Optics.

“This proof-of-concept study demonstrates that this technology may allow for real-time monitoring of prostate cancer in patients during the course of active surveillance. For patients with more aggressive disease, the technology could offer more precise targeting of biopsies to confirm the need for definitive therapy,” said senior author Kent Nastiuk, PhD, assistant professor of cancer genetics and genitourinary cancers at RPCI. “This technology offers the potential to confirm the initial prostate cancer diagnosis, guide biopsies and monitor tumor volume — which is currently not measureable — for improved case management and treatment decision-making.”

PAI uses non-ionizing laser pulses delivered into biological tissues. Some of the delivered energy is absorbed and converted into heat, leading to transient thermoelastic expansion, and thus wideband ultrasonic emission, which can be detected by ultrasonic transducers and analyzed to produce images. The magnitude of the photoacoustic signal is proportional to the local energy deposition, which can be demonstrated by optical absorption contrast on the images of the targeted areas.

Related Links:
Roswell Park Cancer Institute
University of Rochester
Rochester Institute of Technology

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67 (36.001205444336): select jos_linkedin.link from jos_linkedin where cat=10

68 (!!!!! 1802.921295166): SELECT fid FROM jos_deeppockets WHERE id=294765326 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294765326 AND published='1' LIMIT 1

69 (91.075897216797): 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=211 ORDER BY `ordering`

70 (496.86431884766): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294765326 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (312.08992004395): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294765326 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (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`

73 (67.949295043945): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (33.855438232422): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (35.04753112793): 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 (34.809112548828): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (!!!!! 2749.9198913574): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (107.0499420166): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (38.862228393555): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (74.148178100586): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294765326 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (39.815902709961): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294765326 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (45.061111450195): 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 (82.015991210938): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (41.961669921875): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (47.922134399414): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (90.837478637695): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (!!!!! 2058.9828491211): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (87.976455688477): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (106.8115234375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

105 (65.088272094727): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

106 (!!!!! 3621.1013793945): 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=294765326 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (770.09201049805): 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=294765326 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (!!!!! 2635.0021362305): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

109 (!!!!! 2034.9025726318): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

110 (138.99803161621): 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=294765326 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (742.91229248047): 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=294765326 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (!!!!! 1015.9015655518): 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 (862.12158203125): 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 (710.01052856445): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

115 (223.87504577637): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

116 (!!!!! 1978.1589508057): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

117 (308.03680419922): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

118 (!!!!! 2006.0539245605): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

119 (313.99726867676): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

120 (!!!!! 1030.9219360352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

121 (166.17774963379): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

122 (!!!!! 5532.97996521): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 104215.14511108): 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 (!!!!! 1006.1264038086): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294765326 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294765326 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 25651.931762695): ( 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 (72.956085205078): ( 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 (!!!!! 2695.0836181641): 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 (331.87866210938): 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 (612.97416687012): 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 (197.8874206543): 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 (430.82237243652): 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 (437.02125549316): 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 (375.98609924316): 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 (44.822692871094): 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 (!!!!! 2245.9030151367): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (!!!!! 4942.1787261963): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (!!!!! 7385.9691619873): SELECT name FROM jos_deeppockets WHERE id=211

138 (!!!!! 8326.0536193848): SELECT name FROM jos_deeppockets WHERE id=211

139 (!!!!! 7909.0595245361): 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 '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (!!!!! 7132.0533752441): 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 '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (!!!!! 8543.9682006836): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

142 (!!!!! 7990.1218414307): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

143 (!!!!! 13480.186462402): TRUNCATE TABLE jos_trademed_module

144 (!!!!! 5152.9407501221): 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=294765326 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (!!!!! 7641.077041626): 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=294765326 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (!!!!! 1190.185546875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (362.87307739258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (398.87428283691): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

149 (213.8614654541): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

150 (!!!!! 2974.9870300293): 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 (!!!!! 1332.9982757568): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

152 (75.101852416992): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

153 (!!!!! 1008.9874267578): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294765326 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294765326 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (44.107437133789): 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=211 or channel_id is null)

155 (344.99168395996): 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=211 or channel_id is null)

156 (!!!!! 4132.0323944092): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (!!!!! 6255.8650970459): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

158 (!!!!! 7387.8765106201): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294765326 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294765326 AND published='1' LIMIT 1

159 (!!!!! 3394.8421478271): select jos_twitters.link from jos_twitters where cat=10

160 (108.00361633301): select jos_facebook.link from jos_facebook where cat=10

161 (197.8874206543): select jos_google_plus.link from jos_google_plus where cat=10

162 (39.100646972656): select jos_linkedin.link from jos_linkedin where cat=10

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