c170ff128903a210d2a56621627d23df pmc_35216349.pdf 1545525fa9acdac6e8448d13edb96c7a563826fa pmc_35216349.pdf 8d6506566d9fcbedb7e01078305974b5551320c2d57a92969bc6220d48576c4b pmc_35216349.pdf Title: Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections—Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection Subject: Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression. Keywords: tuberculosis; SARS-CoV-2 infection; COVID-19; M. tuberculosis infection; Th cell subsets Author: Anna A. Starshinova, Igor Kudryavtsev, Anna Malkova, Ulia Zinchenko, Vadim Karev, Dmitry Kudlay, Angela Glushkova, Anastasiya Y. Starshinova, Jose Dominguez, Raquel Villar-Hernández, Irina Dovgalyk and Piotr Yablonskiy Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Feb 21 04:21:53 2022 CET ModDate: Mon Feb 21 04:26:39 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2806253 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GVSNKN+VnURWPalladioL Type 1 Custom yes yes no 10 0 IBCMFN+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 GGKXUD+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 JYRAAN+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 FBVPJX+URWPalladioL-BoldItal Type 1 Custom yes yes no 28 0 AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 40 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 44 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 48 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 60 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 63 0 GOCQIR+EURM10 Type 1 Builtin yes yes no 91 0 SOSCBV+CMSY10 Type 1 Builtin yes yes no 98 0 FDKPMA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 122 0 FDKPNC+PalatinoLinotype TrueType WinAnsi yes yes no 125 0 FDKPNE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 128 0 FDKPMA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 144 0 FDKPNC+PalatinoLinotype TrueType WinAnsi yes yes no 147 0 FDKPNE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 150 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-16 02:35:47 CEST RepresentationInformation: pmc_35216349.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-06 18:36:35 CET Size: 2806253 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 416 FreeObjects: 3 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Tuberculosis Diagnosis in the COVID-19 Pandemic Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Pathogenesis of M. tuberculosis (Mtb) and SARS-CoV-2 Infections Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Info: Title: Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection Author: Anna A. Starshinova, Igor Kudryavtsev, Anna Malkova, Ulia Zinchenko, Vadim Karev, Dmitry Kudlay, Angela Glushkova, Anastasiya Y. Starshinova, Jose Dominguez, Raquel Villar-Hernández, Irina Dovgalyk and Piotr Yablonskiy Subject: Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression. Keywords: tuberculosis; SARS-CoV-2 infection; COVID-19; M. tuberculosis infection; Th cell subsets Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Feb 21 04:21:53 CET 2022 ModDate: Mon Feb 21 04:26:39 CET 2022 ID: 0xfafe36dded4290f24ad4a3eb06606fcb, 0xfafe36dded4290f24ad4a3eb06606fcb Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: AIQCCL+VnURWPalladioL-Bold FontSubset: true FirstChar: 161 LastChar: 161 FontDescriptor: FontName: AIQCCL+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: SOSCBV+CMSY10 FontSubset: true FirstChar: 0 LastChar: 2 FontDescriptor: FontName: SOSCBV+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: GGKXUD+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 248 FontDescriptor: FontName: GGKXUD+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: JYRAAN+URWPalladioL-Ital FontSubset: true FirstChar: 45 LastChar: 121 FontDescriptor: FontName: JYRAAN+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: GVSNKN+VnURWPalladioL FontSubset: true FirstChar: 160 LastChar: 226 FontDescriptor: FontName: GVSNKN+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: GOCQIR+EURM10 FontSubset: true FirstChar: 11 LastChar: 13 FontDescriptor: FontName: GOCQIR+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: FBVPJX+URWPalladioL-BoldItal FontSubset: true FirstChar: 40 LastChar: 117 FontDescriptor: FontName: FBVPJX+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: IBCMFN+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 151 FontDescriptor: FontName: IBCMFN+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 34, 323, 152, 332 Annotation: Subtype: Link Rect: 34, 311, 77, 320 Annotation: Subtype: Link Rect: 34, 164, 96, 186 Annotation: Subtype: Link Rect: 126, 90, 154, 99 Annotation: Subtype: Link Rect: 34, 78, 147, 87 Annotation: Subtype: Link Rect: 34, 756, 180, 792 Annotation: Subtype: Link Rect: 515, 756, 560, 792 Annotation: Subtype: Link Rect: 313, 642, 324, 655 Annotation: Subtype: Link Rect: 404, 642, 416, 655 Annotation: Subtype: Link Rect: 117, 629, 128, 643 Annotation: Subtype: Link Rect: 180, 616, 191, 630 Annotation: Subtype: Link Rect: 196, 98, 203, 106 ActionDest: 161 Annotation: Subtype: Link Rect: 204, 98, 211, 106 ActionDest: 161 Annotation: Subtype: Link Rect: 361, 85, 368, 94 ActionDest: 161 Annotation: Subtype: Link Rect: 139, 17, 278, 28 Annotation: Subtype: Link Rect: 422, 17, 560, 28 Annotation: Subtype: Link Rect: 34, 468, 86, 487 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 489, 736, 496, 744 ActionDest: 161 Annotation: Subtype: Link Rect: 491, 685, 498, 694 ActionDest: 161 Annotation: Subtype: Link Rect: 549, 673, 556, 682 ActionDest: 161 Annotation: Subtype: Link Rect: 535, 647, 542, 657 ActionDest: 161 Annotation: Subtype: Link Rect: 488, 623, 495, 631 ActionDest: 161 Annotation: Subtype: Link Rect: 196, 585, 203, 594 ActionDest: 161 Annotation: Subtype: Link Rect: 256, 560, 263, 569 ActionDest: 161 Annotation: Subtype: Link Rect: 256, 535, 263, 544 ActionDest: 161 Annotation: Subtype: Link Rect: 541, 510, 548, 519 ActionDest: 161 Annotation: Subtype: Link Rect: 549, 509, 556, 519 ActionDest: 161 Annotation: Subtype: Link Rect: 343, 447, 350, 456 ActionDest: 161 Annotation: Subtype: Link Rect: 525, 434, 532, 443 ActionDest: 161 Annotation: Subtype: Link Rect: 397, 406, 517, 418 Annotation: Subtype: Link Rect: 512, 321, 524, 330 ActionDest: 161 Annotation: Subtype: Link Rect: 346, 284, 358, 293 ActionDest: 161 Annotation: Subtype: Link Rect: 507, 271, 514, 280 ActionDest: 161 Annotation: Subtype: Link Rect: 549, 246, 556, 255 ActionDest: 161 Annotation: Subtype: Link Rect: 415, 233, 427, 242 ActionDest: 161 Annotation: Subtype: Link Rect: 428, 233, 440, 242 ActionDest: 161 Annotation: Subtype: Link Rect: 376, 158, 388, 167 ActionDest: 161 Annotation: Subtype: Link Rect: 498, 108, 510, 117 ActionDest: 161 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 534, 698, 545, 707 ActionDest: 165 Annotation: Subtype: Link Rect: 485, 660, 497, 669 ActionDest: 161 Annotation: Subtype: Link Rect: 528, 635, 540, 644 ActionDest: 165 Annotation: Subtype: Link Rect: 270, 610, 277, 619 ActionDest: 161 Annotation: Subtype: Link Rect: 394, 597, 406, 606 ActionDest: 165 Annotation: Subtype: Link Rect: 267, 572, 279, 581 ActionDest: 161 Annotation: Subtype: Link Rect: 421, 522, 433, 531 ActionDest: 165 Annotation: Subtype: Link Rect: 217, 497, 229, 506 ActionDest: 161 Annotation: Subtype: Link Rect: 290, 409, 301, 418 ActionDest: 165 Annotation: Subtype: Link Rect: 391, 359, 403, 368 ActionDest: 165 Annotation: Subtype: Link Rect: 263, 321, 275, 330 ActionDest: 165 Annotation: Subtype: Link Rect: 509, 221, 521, 230 ActionDest: 165 Annotation: Subtype: Link Rect: 196, 170, 208, 179 ActionDest: 165 Annotation: Subtype: Link Rect: 331, 95, 343, 104 ActionDest: 165 Annotation: Subtype: Link Rect: 330, 70, 342, 79 ActionDest: 165 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 193, 710, 205, 719 ActionDest: 165 Annotation: Subtype: Link Rect: 386, 673, 398, 682 ActionDest: 165 Annotation: Subtype: Link Rect: 399, 673, 411, 682 ActionDest: 165 Annotation: Subtype: Link Rect: 524, 597, 536, 606 ActionDest: 165 Annotation: Subtype: Link Rect: 239, 522, 251, 531 ActionDest: 161 Annotation: Subtype: Link Rect: 334, 497, 341, 506 ActionDest: 161 Annotation: Subtype: Link Rect: 490, 409, 502, 418 ActionDest: 165 Annotation: Subtype: Link Rect: 511, 359, 523, 368 ActionDest: 161 Annotation: Subtype: Link Rect: 523, 359, 535, 368 ActionDest: 165 Annotation: Subtype: Link Rect: 360, 296, 371, 305 ActionDest: 165 Annotation: Subtype: Link Rect: 372, 296, 384, 305 ActionDest: 165 Annotation: Subtype: Link Rect: 485, 271, 497, 280 ActionDest: 165 Annotation: Subtype: Link Rect: 498, 271, 510, 280 ActionDest: 165 Annotation: Subtype: Link Rect: 360, 221, 372, 230 ActionDest: 161 Annotation: Subtype: Link Rect: 373, 221, 385, 230 ActionDest: 165 Annotation: Subtype: Link Rect: 313, 183, 325, 192 ActionDest: 165 Annotation: Subtype: Link Rect: 434, 145, 446, 154 ActionDest: 165 Annotation: Subtype: Link Rect: 399, 133, 411, 142 ActionDest: 165 Annotation: Subtype: Link Rect: 201, 95, 213, 104 ActionDest: 165 Annotation: Subtype: Link Rect: 430, 70, 442, 79 ActionDest: 165 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 350, 723, 362, 732 ActionDest: 165 Annotation: Subtype: Link Rect: 464, 673, 476, 682 ActionDest: 165 Annotation: Subtype: Link Rect: 224, 635, 231, 644 ActionDest: 161 Annotation: Subtype: Link Rect: 232, 635, 244, 644 ActionDest: 165 Annotation: Subtype: Link Rect: 508, 535, 520, 544 ActionDest: 165 Annotation: Subtype: Link Rect: 326, 484, 338, 493 ActionDest: 165 Annotation: Subtype: Link Rect: 316, 459, 328, 468 ActionDest: 165 Annotation: Subtype: Link Rect: 277, 434, 289, 443 ActionDest: 168 Annotation: Subtype: Link Rect: 531, 422, 543, 431 ActionDest: 168 Annotation: Subtype: Link Rect: 544, 422, 556, 431 ActionDest: 168 Annotation: Subtype: Link Rect: 203, 384, 215, 393 ActionDest: 168 Annotation: Subtype: Link Rect: 510, 334, 522, 343 ActionDest: 168 Annotation: Subtype: Link Rect: 279, 271, 291, 280 ActionDest: 168 Annotation: Subtype: Link Rect: 342, 233, 354, 242 ActionDest: 168 Annotation: Subtype: Link Rect: 440, 221, 452, 230 ActionDest: 168 Annotation: Subtype: Link Rect: 544, 208, 556, 217 ActionDest: 168 Annotation: Subtype: Link Rect: 415, 170, 427, 180 ActionDest: 168 Annotation: Subtype: Link Rect: 441, 95, 453, 104 ActionDest: 168 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 419, 723, 431, 732 ActionDest: 168 Annotation: Subtype: Link Rect: 395, 685, 407, 694 ActionDest: 168 Annotation: Subtype: Link Rect: 450, 622, 462, 631 ActionDest: 165 Annotation: Subtype: Link Rect: 448, 597, 460, 606 ActionDest: 168 Annotation: Subtype: Link Rect: 306, 572, 318, 581 ActionDest: 165 Annotation: Subtype: Link Rect: 275, 522, 286, 531 ActionDest: 168 Annotation: Subtype: Link Rect: 194, 497, 206, 506 ActionDest: 168 Annotation: Subtype: Link Rect: 416, 447, 428, 456 ActionDest: 168 Annotation: Subtype: Link Rect: 479, 422, 491, 431 ActionDest: 168 Annotation: Subtype: Link Rect: 469, 359, 481, 368 ActionDest: 168 Annotation: Subtype: Link Rect: 530, 334, 542, 343 ActionDest: 168 Annotation: Subtype: Link Rect: 281, 271, 293, 280 ActionDest: 168 Annotation: Subtype: Link Rect: 260, 233, 272, 242 ActionDest: 168 Annotation: Subtype: Link Rect: 219, 196, 231, 205 ActionDest: 168 Annotation: Subtype: Link Rect: 365, 145, 376, 154 ActionDest: 168 Annotation: Subtype: Link Rect: 440, 70, 452, 79 ActionDest: 168 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 523, 723, 535, 732 ActionDest: 168 Annotation: Subtype: Link Rect: 209, 673, 221, 682 ActionDest: 168 Annotation: Subtype: Link Rect: 325, 673, 337, 682 ActionDest: 168 Annotation: Subtype: Link Rect: 453, 673, 465, 682 ActionDest: 171 Annotation: Subtype: Link Rect: 213, 660, 225, 669 ActionDest: 171 Annotation: Subtype: Link Rect: 333, 660, 345, 669 ActionDest: 171 Annotation: Subtype: Link Rect: 412, 622, 424, 631 ActionDest: 171 Annotation: Subtype: Link Rect: 427, 622, 439, 631 ActionDest: 171 Annotation: Subtype: Link Rect: 331, 597, 343, 606 ActionDest: 165 Annotation: Subtype: Link Rect: 414, 585, 426, 594 ActionDest: 171 Annotation: Subtype: Link Rect: 287, 560, 299, 569 ActionDest: 171 Annotation: Subtype: Link Rect: 199, 532, 206, 544 ActionDest: 105 Annotation: Subtype: Link Rect: 237, 229, 249, 238 ActionDest: 171 Annotation: Subtype: Link Rect: 479, 229, 491, 238 ActionDest: 171 Annotation: Subtype: Link Rect: 226, 153, 238, 162 ActionDest: 171 Annotation: Subtype: Link Rect: 248, 116, 255, 125 ActionDest: 161 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 199, 695, 206, 707 ActionDest: 138 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 344, 126, 351, 138 ActionDest: 138 Annotation: Subtype: Link Rect: 256, 91, 268, 100 ActionDest: 171 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 238, 660, 250, 669 ActionDest: 171 Annotation: Subtype: Link Rect: 403, 559, 414, 568 ActionDest: 165 Annotation: Subtype: Link Rect: 314, 509, 326, 518 ActionDest: 171 Annotation: Subtype: Link Rect: 329, 509, 341, 518 ActionDest: 171 Annotation: Subtype: Link Rect: 379, 371, 391, 380 ActionDest: 171 Annotation: Subtype: Link Rect: 353, 214, 365, 224 ActionDest: 165 Annotation: Subtype: Link Rect: 457, 164, 469, 173 ActionDest: 171 Annotation: Subtype: Link Rect: 469, 164, 481, 173 ActionDest: 171 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 409, 340, 446, 351 Annotation: Subtype: Link Rect: 452, 340, 488, 351 Annotation: Subtype: Link Rect: 492, 329, 529, 340 Annotation: Subtype: Link Rect: 519, 271, 557, 282 Annotation: Subtype: Link Rect: 59, 260, 95, 271 Annotation: Subtype: Link Rect: 358, 214, 395, 225 Annotation: Subtype: Link Rect: 270, 190, 307, 201 Annotation: Subtype: Link Rect: 95, 168, 133, 178 Annotation: Subtype: Link Rect: 348, 145, 386, 155 Annotation: Subtype: Link Rect: 280, 121, 317, 132 Annotation: Subtype: Link Rect: 347, 98, 385, 109 Annotation: Subtype: Link Rect: 95, 76, 133, 86 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 399, 722, 437, 733 Annotation: Subtype: Link Rect: 443, 722, 479, 733 Annotation: Subtype: Link Rect: 95, 688, 133, 698 Annotation: Subtype: Link Rect: 139, 688, 175, 698 Annotation: Subtype: Link Rect: 348, 664, 385, 675 Annotation: Subtype: Link Rect: 161, 641, 199, 652 Annotation: Subtype: Link Rect: 297, 606, 335, 617 Annotation: Subtype: Link Rect: 113, 584, 151, 594 Annotation: Subtype: Link Rect: 157, 584, 193, 594 Annotation: Subtype: Link Rect: 139, 561, 177, 571 Annotation: Subtype: Link Rect: 481, 537, 518, 548 Annotation: Subtype: Link Rect: 135, 504, 173, 514 Annotation: Subtype: Link Rect: 149, 481, 186, 491 Annotation: Subtype: Link Rect: 494, 468, 531, 479 Annotation: Subtype: Link Rect: 193, 434, 231, 445 Annotation: Subtype: Link Rect: 341, 411, 379, 422 Annotation: Subtype: Link Rect: 385, 411, 421, 422 Annotation: Subtype: Link Rect: 395, 388, 433, 399 Annotation: Subtype: Link Rect: 431, 365, 468, 376 Annotation: Subtype: Link Rect: 475, 365, 511, 376 Annotation: Subtype: Link Rect: 59, 331, 96, 341 Annotation: Subtype: Link Rect: 102, 331, 138, 341 Annotation: Subtype: Link Rect: 332, 307, 369, 318 Annotation: Subtype: Link Rect: 86, 262, 124, 272 Annotation: Subtype: Link Rect: 104, 228, 141, 238 Annotation: Subtype: Link Rect: 148, 228, 184, 238 Annotation: Subtype: Link Rect: 243, 204, 280, 215 Annotation: Subtype: Link Rect: 287, 204, 323, 215 Annotation: Subtype: Link Rect: 435, 192, 473, 203 Annotation: Subtype: Link Rect: 479, 192, 515, 203 Annotation: Subtype: Link Rect: 95, 170, 133, 180 Annotation: Subtype: Link Rect: 139, 170, 175, 180 Annotation: Subtype: Link Rect: 224, 146, 262, 157 Annotation: Subtype: Link Rect: 268, 146, 304, 157 Annotation: Subtype: Link Rect: 184, 89, 222, 100 Annotation: Subtype: Link Rect: 520, 66, 557, 77 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 178, 722, 215, 733 Annotation: Subtype: Link Rect: 258, 699, 295, 710 Annotation: Subtype: Link Rect: 500, 676, 537, 687 Annotation: Subtype: Link Rect: 230, 641, 268, 652 Annotation: Subtype: Link Rect: 473, 618, 511, 629 Annotation: Subtype: Link Rect: 211, 584, 249, 594 Annotation: Subtype: Link Rect: 81, 550, 119, 560 Annotation: Subtype: Link Rect: 125, 550, 161, 560 Annotation: Subtype: Link Rect: 197, 527, 234, 537 Annotation: Subtype: Link Rect: 241, 527, 277, 537 Annotation: Subtype: Link Rect: 440, 503, 477, 514 Annotation: Subtype: Link Rect: 484, 503, 520, 514 Annotation: Subtype: Link Rect: 156, 469, 194, 479 Annotation: Subtype: Link Rect: 326, 445, 364, 456 Annotation: Subtype: Link Rect: 281, 411, 319, 422 Annotation: Subtype: Link Rect: 242, 388, 280, 399 Annotation: Subtype: Link Rect: 195, 353, 233, 364 Annotation: Subtype: Link Rect: 416, 330, 454, 341 Annotation: Subtype: Link Rect: 285, 296, 322, 307 Annotation: Subtype: Link Rect: 117, 262, 155, 272 Annotation: Subtype: Link Rect: 282, 227, 319, 238 Annotation: Subtype: Link Rect: 326, 227, 362, 238 Annotation: Subtype: Link Rect: 59, 193, 96, 203 Annotation: Subtype: Link Rect: 102, 193, 138, 203 Annotation: Subtype: Link Rect: 366, 158, 404, 169 Annotation: Subtype: Link Rect: 410, 158, 446, 169 Annotation: Subtype: Link Rect: 59, 124, 96, 134 Annotation: Subtype: Link Rect: 126, 90, 164, 100 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 319, 710, 356, 721 Annotation: Subtype: Link Rect: 59, 676, 96, 687 Annotation: Subtype: Link Rect: 385, 652, 422, 664 Annotation: Subtype: Link Rect: 268, 629, 305, 640 Annotation: Subtype: Link Rect: 311, 629, 348, 640 Annotation: Subtype: Link Rect: 519, 606, 557, 617 Annotation: Subtype: Link Rect: 59, 596, 95, 606 Annotation: Subtype: Link Rect: 421, 572, 458, 583 Annotation: Subtype: Link Rect: 464, 572, 501, 583 Annotation: Subtype: Link Rect: 59, 538, 96, 548 Annotation: Subtype: Link Rect: 169, 504, 207, 514 Annotation: Subtype: Link Rect: 290, 480, 327, 491 Annotation: Subtype: Link Rect: 328, 457, 366, 468 Annotation: Subtype: Link Rect: 138, 422, 176, 433 Annotation: Subtype: Link Rect: 86, 389, 123, 399 Annotation: Subtype: Link Rect: 263, 354, 301, 364 Annotation: Subtype: Link Rect: 357, 330, 395, 341 Annotation: Subtype: Link Rect: 401, 330, 437, 341 Annotation: Subtype: Link Rect: 376, 307, 413, 318 Annotation: Subtype: Link Rect: 419, 307, 455, 318 Annotation: Subtype: Link Rect: 131, 274, 168, 284 Checksum: 5f9175b1 Type: CRC32 Checksum: c170ff128903a210d2a56621627d23df Type: MD5 Checksum: 1545525fa9acdac6e8448d13edb96c7a563826fa Type: SHA-1