4070c5e4c6933bf9f5bbca45ac332763 metabolites_a2019v9n12p288.pdf f29b011f882d0b66253f4be1d2399721f79ce2aa metabolites_a2019v9n12p288.pdf 116f6cc447139488c49f2a6476c0c67e7079361be45a06cbeec065e42430a038 metabolites_a2019v9n12p288.pdf Title: 1H-NMR Urinary Metabolic Profile, A Promising Tool for the Management of Infants with Human Cytomegalovirus-Infection Subject: Congenital human cytomegalovirus (HCMV) infection is the most common mother-to-child transmitted infection in the developed world. Certain aspects of its management remain a challenge. Urinary metabolic profiling is a promising tool for use in pediatric conditions. The aim of this study was to investigate the urinary metabolic profile in HCMV-infected infants and controls during acute care hospitalization. Urine samples were collected from 53 patients at five hospitals participating in the Spanish congenital HCMV registry. Thirty-one cases of HCMV infection and 22 uninfected controls were included. Proton nuclear magnetic resonance (1H-NMR) spectra were obtained using NOESYPR1D pulse sequence. The dataset underwent orthogonal projection on latent structures discriminant analysis to identify candidate variables affecting the urinary metabolome: HCMV infection, type of infection, sex, chronological age, gestational age, type of delivery, twins, and diet. Statistically significant discriminative models were obtained only for HCMV infection (p = 0.03) and chronological age (p < 0.01). No significant differences in the metabolomic profile were found between congenital and postnatal HCMV infection. When the HCMV-infected group was analyzed according to chronological age, a statistically significant model was obtained only in the neonatal group (p = 0.01), with the differentiating metabolites being betaine, glycine, alanine, and dimethylamine. Despite the considerable variation in urinary metabolic profiles in a real-life setting, clinical application of metabolomics to the study of HCMV infection seems feasible. Keywords: human cytomegalovirus; congenital infection; pediatrics; metabolomics; 1H-NMR; metabolic profiling Author: Marie Antoinette Frick, Ignasi Barba, Marina Fenoy-Alejandre, Paula López-López, Fernando Baquero-Artigao, Paula Rodríguez-Molino, Antoni Noguera-Julian, Marta Nicolás-López, Asunción de la Fuente-Juárez, Maria Gemma Codina-Grau, Juliana Esperalba Esquerra, Ángeles Linde-Sillo and Pere Soler-Palacín Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Mon Nov 25 10:22:00 2019 CET ModDate: Mon Apr 19 10:23:53 2021 CEST 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: 936534 bytes Optimized: yes PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WIPXQR+VnURWPalladioL-Bold Type 1 Custom yes yes no 474 0 YCUWLT+VnURWPalladioL Type 1 Custom yes yes no 477 0 OLPJHJ+URWPalladioL-Ital Type 1 Custom yes yes no 481 0 LIZQTE+URWPalladioL-Bold Type 1 Custom yes yes no 484 0 DLSHXU+URWPalladioL-Roma Type 1 Custom yes yes no 487 0 OFLXAT+Rpxr Type 1 Builtin yes yes no 490 0 ZZPUEX+ArialMT Type 1C WinAnsi yes yes no 495 0 TWGUDY+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 497 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 509 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 512 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 515 0 WWQLWV+Pxsy Type 1 Builtin yes yes no 271 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 270 0 GPHKHI+PalatinoLinotype TrueType WinAnsi yes yes no 126 0 GPHKMI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 128 0 GPHKMK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 130 0 GPHLEI+TimesNewRoman CID TrueType Identity-H yes yes yes 133 0 GPHKHI+PalatinoLinotype TrueType WinAnsi yes yes no 144 0 GPHKMI+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 146 0 GPHKMK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 148 0 GPHLEI+TimesNewRoman CID TrueType Identity-H yes yes yes 151 0 GPHLOG+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 153 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 272 0 TGMEOR+Rpcxr Type 1 Builtin yes yes no 274 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-01 02:36:30 CET RepresentationInformation: metabolites_a2019v9n12p288.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-02-28 16:14:29 CET Size: 936534 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Linearized PDF PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Results Children: Item: Title: Patients Item: Title: Pattern Recognition Item: Title: Discussion Item: Title: Materials and Methods Children: Item: Title: Patients Item: Title: Definitions Item: Title: Samples Item: Title: NMR Spectroscopy Item: Title: Data Analysis Item: Title: References Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: OVNEXW+EURM10 FontSubset: true FirstChar: 22 LastChar: 22 FontDescriptor: FontName: OVNEXW+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: OLPJHJ+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: OLPJHJ+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: TGMEOR+Rpcxr FontSubset: true FirstChar: 169 LastChar: 174 FontDescriptor: FontName: TGMEOR+Rpcxr Flags: Symbolic FontBBox: -212, -286, 1344, 973 FontFile: true Font: BaseFont: LIZQTE+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 136 FontDescriptor: FontName: LIZQTE+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: DLSHXU+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 246 FontDescriptor: FontName: DLSHXU+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: OFLXAT+Rpxr FontSubset: true FirstChar: 11 LastChar: 62 FontDescriptor: FontName: OFLXAT+Rpxr Flags: Symbolic FontBBox: -40, -283, 904, 728 FontFile: true Font: BaseFont: WIPXQR+VnURWPalladioL-Bold FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: WIPXQR+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: YCUWLT+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: YCUWLT+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WBVKDJ+URWPalladioL-BoldItal FontSubset: true FirstChar: 112 LastChar: 112 FontDescriptor: FontName: WBVKDJ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: WWQLWV+Pxsy FontSubset: true FirstChar: 0 LastChar: 20 FontDescriptor: FontName: WWQLWV+Pxsy Flags: Symbolic FontBBox: -21, -994, 1292, 912 FontFile: true XMP: application/pdf Marie Antoinette Frick, Ignasi Barba, Marina Fenoy-Alejandre, Paula López-López, Fernando Baquero-Artigao, Paula Rodríguez-Molino, Antoni Noguera-Julian, Marta Nicolás-López, Asunción de la Fuente-Juárez, Maria Gemma Codina-Grau, Juliana Esperalba Esquerra, Ángeles Linde-Sillo and Pere Soler-Palacín Congenital human cytomegalovirus (HCMV) infection is the most common mother-to-child transmitted infection in the developed world. Certain aspects of its management remain a challenge. Urinary metabolic profiling is a promising tool for use in pediatric conditions. The aim of this study was to investigate the urinary metabolic profile in HCMV-infected infants and controls during acute care hospitalization. Urine samples were collected from 53 patients at five hospitals participating in the Spanish congenital HCMV registry. Thirty-one cases of HCMV infection and 22 uninfected controls were included. Proton nuclear magnetic resonance (1H-NMR) spectra were obtained using NOESYPR1D pulse sequence. The dataset underwent orthogonal projection on latent structures discriminant analysis to identify candidate variables affecting the urinary metabolome: HCMV infection, type of infection, sex, chronological age, gestational age, type of delivery, twins, and diet. Statistically significant discriminative models were obtained only for HCMV infection (p = 0.03) and chronological age (p < 0.01). No significant differences in the metabolomic profile were found between congenital and postnatal HCMV infection. When the HCMV-infected group was analyzed according to chronological age, a statistically significant model was obtained only in the neonatal group (p = 0.01), with the differentiating metabolites being betaine, glycine, alanine, and dimethylamine. Despite the considerable variation in urinary metabolic profiles in a real-life setting, clinical application of metabolomics to the study of HCMV infection seems feasible. 1H-NMR Urinary Metabolic Profile, A Promising Tool for the Management of Infants with Human Cytomegalovirus-Infection 2019-11-25T17:22+08:00 LaTeX with hyperref package 2021-04-19T10:23:53+02:00 2021-04-19T10:23:53+02:00 human cytomegalovirus; congenital infection; pediatrics; metabolomics; 1H-NMR; metabolic profiling pdfTeX-1.40.18 False This is pdfTeX, Version 3.14159265-2.6-1.40.18 (TeX Live 2017/W32TeX) kpathsea version 6.2.3 uuid:f6fdea83-b583-4aa2-8d04-40be0af944aa uuid:c7941314-8117-4e38-ae84-765975f49f2b Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 75, 757, 207, 793 Annotation: Subtype: Link Rect: 474, 757, 519, 793 Annotation: Subtype: Link Rect: 471, 628, 482, 641 Annotation: Subtype: Link Rect: 466, 282, 518, 301 Annotation: Subtype: Link Rect: 172, 38, 256, 50 Annotation: Subtype: Link Rect: 390, 38, 519, 50 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 107, 525, 113, 534 ActionDest: 50 Annotation: Subtype: Link Rect: 114, 525, 121, 534 ActionDest: 50 Annotation: Subtype: Link Rect: 132, 498, 139, 507 ActionDest: 50 Annotation: Subtype: Link Rect: 140, 498, 147, 507 ActionDest: 50 Annotation: Subtype: Link Rect: 147, 498, 154, 507 ActionDest: 50 Annotation: Subtype: Link Rect: 189, 484, 196, 494 ActionDest: 50 Annotation: Subtype: Link Rect: 196, 484, 203, 494 ActionDest: 50 Annotation: Subtype: Link Rect: 443, 417, 450, 426 ActionDest: 53 Annotation: Subtype: Link Rect: 450, 417, 457, 426 ActionDest: 53 Annotation: Subtype: Link Rect: 388, 336, 395, 345 ActionDest: 53 Annotation: Subtype: Link Rect: 396, 336, 408, 345 ActionDest: 53 Annotation: Subtype: Link Rect: 187, 309, 194, 318 ActionDest: 53 Annotation: Subtype: Link Rect: 425, 268, 437, 277 ActionDest: 53 Annotation: Subtype: Link Rect: 440, 268, 452, 277 ActionDest: 53 Annotation: Subtype: Link Rect: 351, 241, 357, 250 ActionDest: 53 Annotation: Subtype: Link Rect: 503, 214, 515, 223 ActionDest: 53 Annotation: Subtype: Link Rect: 358, 174, 365, 183 ActionDest: 50 Annotation: Subtype: Link Rect: 365, 174, 372, 183 ActionDest: 53 Annotation: Subtype: Link Rect: 373, 174, 380, 183 ActionDest: 53 Annotation: Subtype: Link Rect: 380, 174, 392, 183 ActionDest: 53 Annotation: Subtype: Link Rect: 395, 174, 407, 183 ActionDest: 53 Annotation: Subtype: Link Rect: 117, 147, 129, 156 ActionDest: 53 Annotation: Subtype: Link Rect: 132, 147, 144, 156 ActionDest: 53 Annotation: Subtype: Link Rect: 402, 93, 414, 102 ActionDest: 53 Annotation: Subtype: Link Rect: 414, 93, 426, 102 ActionDest: 53 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 379, 702, 386, 711 ActionDest: 50 Annotation: Subtype: Link Rect: 387, 702, 399, 711 ActionDest: 53 Annotation: Subtype: Link Rect: 399, 702, 411, 711 ActionDest: 53 Annotation: Subtype: Link Rect: 160, 675, 167, 684 ActionDest: 50 Annotation: Subtype: Link Rect: 168, 675, 180, 684 ActionDest: 53 Annotation: Subtype: Link Rect: 180, 675, 192, 684 ActionDest: 53 Annotation: Subtype: Link Rect: 195, 675, 207, 684 ActionDest: 56 Annotation: Subtype: Link Rect: 293, 634, 305, 644 ActionDest: 53 Annotation: Subtype: Link Rect: 305, 634, 317, 644 ActionDest: 56 Annotation: Subtype: Link Rect: 403, 607, 415, 617 ActionDest: 56 Annotation: Subtype: Link Rect: 386, 526, 398, 535 ActionDest: 56 Annotation: Subtype: Link Rect: 160, 339, 167, 348 ActionDest: 4 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 295, 441, 302, 453 ActionDest: 10 Annotation: Subtype: Link Rect: 343, 387, 350, 399 ActionDest: 10 Annotation: Subtype: Link Rect: 379, 374, 386, 385 ActionDest: 10 Annotation: Subtype: Link Rect: 424, 374, 431, 385 ActionDest: 7 Page: Sequence: 5 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 391, 726, 398, 738 ActionDest: 10 Annotation: Subtype: Link Rect: 129, 686, 136, 698 ActionDest: 10 Annotation: Subtype: Link Rect: 109, 591, 116, 603 ActionDest: 23 Annotation: Subtype: Link Rect: 272, 353, 279, 365 ActionDest: 23 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 314, 429, 321, 440 ActionDest: 37 Annotation: Subtype: Link Rect: 339, 429, 346, 440 ActionDest: 37 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 108, 588, 120, 597 ActionDest: 56 Annotation: Subtype: Link Rect: 388, 574, 395, 584 ActionDest: 53 Annotation: Subtype: Link Rect: 367, 547, 379, 557 ActionDest: 56 Annotation: Subtype: Link Rect: 455, 507, 467, 516 ActionDest: 56 Annotation: Subtype: Link Rect: 395, 385, 407, 394 ActionDest: 56 Annotation: Subtype: Link Rect: 204, 358, 216, 367 ActionDest: 56 Annotation: Subtype: Link Rect: 234, 209, 245, 219 ActionDest: 53 Annotation: Subtype: Link Rect: 246, 209, 258, 219 ActionDest: 56 Annotation: Subtype: Link Rect: 337, 196, 349, 205 ActionDest: 56 Annotation: Subtype: Link Rect: 318, 142, 325, 151 ActionDest: 53 Annotation: Subtype: Link Rect: 325, 142, 337, 151 ActionDest: 56 Annotation: Subtype: Link Rect: 340, 142, 352, 151 ActionDest: 56 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 165, 715, 172, 725 ActionDest: 53 Annotation: Subtype: Link Rect: 148, 580, 160, 590 ActionDest: 56 Annotation: Subtype: Link Rect: 132, 526, 144, 535 ActionDest: 53 Annotation: Subtype: Link Rect: 144, 526, 156, 535 ActionDest: 56 Annotation: Subtype: Link Rect: 137, 486, 149, 495 ActionDest: 53 Annotation: Subtype: Link Rect: 150, 486, 162, 495 ActionDest: 53 Annotation: Subtype: Link Rect: 162, 486, 174, 495 ActionDest: 53 Annotation: Subtype: Link Rect: 175, 486, 187, 495 ActionDest: 56 Annotation: Subtype: Link Rect: 190, 486, 202, 495 ActionDest: 56 Annotation: Subtype: Link Rect: 242, 337, 254, 346 ActionDest: 53 Annotation: Subtype: Link Rect: 254, 337, 266, 346 ActionDest: 56 Annotation: Subtype: Link Rect: 225, 175, 237, 184 ActionDest: 56 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 296, 89, 308, 98 ActionDest: 56 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 325, 551, 332, 560 ActionDest: 53 Annotation: Subtype: Link Rect: 332, 551, 344, 560 ActionDest: 56 Annotation: Subtype: Link Rect: 347, 551, 359, 560 ActionDest: 59 Annotation: Subtype: Link Rect: 337, 527, 518, 538 Annotation: Subtype: Link Rect: 422, 505, 428, 516 ActionDest: 7 Annotation: Subtype: Link Rect: 435, 266, 472, 277 Annotation: Subtype: Link Rect: 479, 266, 515, 277 Annotation: Subtype: Link Rect: 479, 228, 516, 238 Annotation: Subtype: Link Rect: 290, 202, 327, 213 Annotation: Subtype: Link Rect: 333, 202, 369, 213 Annotation: Subtype: Link Rect: 100, 164, 137, 174 Annotation: Subtype: Link Rect: 100, 112, 137, 122 Annotation: Subtype: Link Rect: 274, 73, 312, 84 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 137, 715, 174, 725 Annotation: Subtype: Link Rect: 346, 688, 383, 699 Annotation: Subtype: Link Rect: 100, 586, 137, 596 Annotation: Subtype: Link Rect: 143, 586, 179, 596 Annotation: Subtype: Link Rect: 479, 546, 516, 557 Annotation: Subtype: Link Rect: 100, 534, 136, 544 Annotation: Subtype: Link Rect: 430, 495, 468, 506 Annotation: Subtype: Link Rect: 474, 495, 510, 506 Annotation: Subtype: Link Rect: 172, 418, 210, 428 Annotation: Subtype: Link Rect: 350, 353, 387, 364 Annotation: Subtype: Link Rect: 248, 327, 286, 338 Annotation: Subtype: Link Rect: 255, 302, 293, 312 Annotation: Subtype: Link Rect: 100, 276, 137, 286 Annotation: Subtype: Link Rect: 100, 250, 137, 260 Annotation: Subtype: Link Rect: 143, 250, 179, 260 Annotation: Subtype: Link Rect: 100, 224, 137, 234 Annotation: Subtype: Link Rect: 143, 224, 179, 234 Annotation: Subtype: Link Rect: 233, 199, 270, 209 Annotation: Subtype: Link Rect: 277, 199, 313, 209 Annotation: Subtype: Link Rect: 281, 173, 318, 183 Annotation: Subtype: Link Rect: 324, 173, 360, 183 Annotation: Subtype: Link Rect: 342, 133, 454, 144 Annotation: Subtype: Link Rect: 364, 94, 402, 105 Annotation: Subtype: Link Rect: 408, 94, 444, 105 Annotation: Subtype: Link Rect: 212, 69, 249, 80 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 274, 714, 312, 725 Annotation: Subtype: Link Rect: 284, 689, 321, 699 Annotation: Subtype: Link Rect: 220, 663, 258, 673 Annotation: Subtype: Link Rect: 349, 624, 386, 635 Annotation: Subtype: Link Rect: 436, 611, 473, 622 Annotation: Subtype: Link Rect: 479, 611, 515, 622 Annotation: Subtype: Link Rect: 237, 586, 275, 596 Annotation: Subtype: Link Rect: 281, 586, 317, 596 Annotation: Subtype: Link Rect: 136, 547, 174, 557 Annotation: Subtype: Link Rect: 180, 547, 216, 557 Annotation: Subtype: Link Rect: 435, 521, 473, 531 Annotation: Subtype: Link Rect: 479, 521, 515, 531 Annotation: Subtype: Link Rect: 467, 508, 504, 519 Annotation: Subtype: Link Rect: 100, 483, 137, 493 Annotation: Subtype: Link Rect: 377, 456, 414, 467 Annotation: Subtype: Link Rect: 334, 417, 371, 428 Annotation: Subtype: Link Rect: 430, 391, 468, 402 Annotation: Subtype: Link Rect: 408, 366, 445, 376 Annotation: Subtype: Link Rect: 235, 341, 273, 351 Annotation: Subtype: Link Rect: 279, 341, 315, 351 Annotation: Subtype: Link Rect: 234, 302, 272, 312 Annotation: Subtype: Link Rect: 278, 302, 314, 312 Annotation: Subtype: Link Rect: 279, 276, 317, 286 Annotation: Subtype: Link Rect: 323, 276, 359, 286 Annotation: Subtype: Link Rect: 341, 250, 379, 260 Annotation: Subtype: Link Rect: 385, 250, 421, 260 Annotation: Subtype: Link Rect: 346, 198, 384, 209 Annotation: Subtype: Link Rect: 244, 173, 282, 183 Annotation: Subtype: Link Rect: 172, 147, 210, 157 Annotation: Subtype: Link Rect: 379, 107, 417, 118 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 380, 727, 418, 738 Annotation: Subtype: Link Rect: 355, 701, 392, 712 Annotation: Subtype: Link Rect: 398, 701, 435, 712 Annotation: Subtype: Link Rect: 76, 659, 166, 690 Annotation: Subtype: Link Rect: 234, 654, 407, 664 Checksum: 208e2a99 Type: CRC32 Checksum: 4070c5e4c6933bf9f5bbca45ac332763 Type: MD5 Checksum: f29b011f882d0b66253f4be1d2399721f79ce2aa Type: SHA-1