Detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT)

The purpose of this study was to analyze the detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). Data for a total of 492 patients who had undergone both PET/CT and colonoscopy were analyzed. After the findings of PET/CT and colonoscopy were determined independently, the results were compared in each of the six colonic sites examined in all patients. The efficacy of PET/CT was determined using colonoscopic examination as the gold standard. In all, 270 colorectal lesions 5 mm or more in size, including 70 pathologically confirmed malignant lesions, were found in 172 patients by colonoscopy. The sensitivity and specificity of PET/CT for detecting any of the colorectal lesions were 36 and 98%, respectively. For detecting lesions 11 mm or larger, the sensitivity was increased to 85%, with the specificity remaining consistent (97%). Moreover, the sensitivity for tumors 21 mm or larger was 96% (48/50). Tumors with malignant or high-grade pathology were likely to be positive with PET/CT. A size of 10 mm or smaller [odds ratio (OR) 44.14, 95% confidence interval (95% CI) 11.44-221.67] and flat morphology (OR 7.78, 95% CI 1.79-36.25) were significant factors that were associated with false-negative cases on PET/CT. The sensitivity of PET/CT for detecting colorectal lesions is acceptable, showing size- and pathology-dependence, suggesting, for the most part, that clinically relevant lesions are detectable with PET/CT. However, when considering PET/CT for screening purposes caution must be exercised because there are cases of false-negative results

Unusually thick dinosaur eggshell fragments from the Spanish Late Cretaceous

[EN] Fieldwork carried out recently in the southeastern branch of the Iberian Range (Valencia Province, Spain) has led to the collection of a large volume of dinosaur eggshell fragments of unusual thickness. These specimens, up to 4.9 mm thick, were recovered from palustrine grey marls of the upper Campanian-lower Maastrichtian Sierra Perenchiza Formation, which comprises a wetland paleoenvironment deposit. These eggshell fragments have a characteristic compactituberculate ornamentation, dinosauroid-spherulitic organisation, and exhibit a complex canaliculate respiratory system. The external tuberculate surface of the shell as well as the internal microstructure enable referral to Megaloolithus aff. siruguei, the most common megaloolithid oospecies known from the Iberian Peninsula and southern France. The biostratigraphic range of M. siruguei matches the temporal distribution of titanosaurid dinosaurs across the Iberian Range, tentatively considered to be potential producers.This work was supported by the Ministerio de Economia y Competitividad of Spain [Secretaria de Estado de Investigacion, Desarrollo e Innovacion, projects CGL2013-47521-P and CGL2014-53548-P]Company Rodríguez, J. (2017). Unusually thick dinosaur eggshell fragments from the Spanish Late Cretaceous. Historical Biology (Online). 31(2):203-210. https://doi.org/10.1080/08912963.2017.1357717S203210312Allain, R., & Suberbiola, X. P. (2003). Dinosaurs of France. Comptes Rendus Palevol, 2(1), 27-44. doi:10.1016/s1631-0683(03)00002-2Bravo, A. M., & Gaete, R. (2014). Titanosaur eggshells from the Tremp Formation (Upper Cretaceous, Southern Pyrenees, Spain). Historical Biology, 27(8), 1079-1089. doi:10.1080/08912963.2014.934231Canudo, J. I., Oms, O., Vila, B., Galobart, À., Fondevilla, V., Puértolas-Pascual, E., … Blanco, A. (2016). The upper Maastrichtian dinosaur fossil record from the southern Pyrenees and its contribution to the topic of the Cretaceous–Palaeogene mass extinction event. Cretaceous Research, 57, 540-551. doi:10.1016/j.cretres.2015.06.013Cruzado-Caballero, P., Ruiz-Omeñaca, J. I., Gaete, R., Riera, V., Oms, O., & Canudo, J. I. (2013). A new hadrosaurid dentary from the latest Maastrichtian of the Pyrenees (north Spain) and the high diversity of the duck-billed dinosaurs of the Ibero-Armorican Realm at the very end of the Cretaceous. Historical Biology, 26(5), 619-630. doi:10.1080/08912963.2013.822867Chiappe, L. M., Coria, R. A., Dingus, L., Jackson, F., Chinsamy, A., & Fox, M. (1998). Sauropod dinosaur embryos from the Late Cretaceous of Patagonia. Nature, 396(6708), 258-261. doi:10.1038/24370Company J. 2004. Vertebrados continentales del Cretácico superior (Campaniense-Maastrichtiense) de Valencia [PhD dissertation]. Valencia: Universidad de Valencia.Company, J., & Szentesi, Z. (2012). Amphibians from the Late Cretaceous Sierra Perenchiza Formation of the Chera Basin, Valencia Province, Spain. Cretaceous Research, 37, 240-245. doi:10.1016/j.cretres.2012.04.003Csiki-Sava, Z., Buffetaut, E., Ősi, A., Pereda-Suberbiola, X., & Brusatte, S. L. (2015). Island life in the Cretaceous - faunal composition, biogeography, evolution, and extinction of land-living vertebrates on the Late Cretaceous European archipelago. ZooKeys, 469, 1-161. doi:10.3897/zookeys.469.8439Erben, H. K., Hoefs, J., & Wedepohl, K. H. (1979). Paleobiological and isotopic studies of eggshells from a declining dinosaur species. Paleobiology, 5(4), 380-414. doi:10.1017/s0094837300016900García, R. A. (2007). An «egg-tooth»–like structure in titanosaurian sauropod embryos. Journal of Vertebrate Paleontology, 27(1), 247-252. doi:10.1671/0272-4634(2007)27[247:aesits]2.0.co;2Garcia, G., & Vianey-Liaud, M. (2001). Dinosaur eggshells as biochronological markers in Upper Cretaceous continental deposits. Palaeogeography, Palaeoclimatology, Palaeoecology, 169(1-2), 153-164. doi:10.1016/s0031-0182(01)00215-2Grellet-Tinner, G., Chiappe, L. M., & Coria, R. (2004). Eggs of titanosaurid sauropods from the Upper Cretaceous of Auca Mahuevo (Argentina). Canadian Journal of Earth Sciences, 41(8), 949-960. doi:10.1139/e04-049Grigorescu, D., Garcia, G., Csiki, Z., Codrea, V., & Bojar, A.-V. (2010). Uppermost Cretaceous megaloolithid eggs from the Haţeg Basin, Romania, associated with hadrosaur hatchlings: Search for explanation. Palaeogeography, Palaeoclimatology, Palaeoecology, 293(3-4), 360-374. doi:10.1016/j.palaeo.2010.03.031Izquierdo LA, Montero D, Pérez G, Urién V, Meijide M. 2001. Macroestructura de huevos de dinosaurios en el Cretácico superior de “La Rosaca” (Burgos, España). Actas de las I Jornadas Internacionales Sobre Paleontología de Dinosaurios y su Entorno. Ed. Colectivo Arqueológico y Paleontológico de Salas. Salas de los Infantes. p. 389–395.Jackson FD. 2007. Titanosaur reproductive biology: comparison of the Auca Mahuevo Titanosaur nesting locality (Argentina), to the Pinyes Megaloolithus nesting locality (Spain) [PhD dissertation]. Bozeman (MT): Montana State University.Jackson, F. D., Garrido, A., Schmitt, J. G., Chiappe, L. M., Dingus, L., & Loope, D. B. (2004). Abnormal, multilayered titanosaur (Dinosauria: Sauropoda) eggs from in situ clutches at the Auca Mahuevo locality, Neuquen Province, Argentina. Journal of Vertebrate Paleontology, 24(4), 913-922. doi:10.1671/0272-4634(2004)024[0913:amtdse]2.0.co;2Jackson, F. D., Varricchio, D. J., Jackson, R. A., Vila, B., & Chiappe, L. M. (2008). Comparison of water vapor conductance in a titanosaur egg from the Upper Cretaceous of Argentina and a Megaloolithus siruguei egg from Spain. Paleobiology, 34(2), 229-246. doi:10.1666/0094-8373(2008)034[0229:cowvci]2.0.co;2López-Martı́nez, N., Moratalla, J. J., & Sanz, J. L. (2000). Dinosaurs nesting on tidal flats. Palaeogeography, Palaeoclimatology, Palaeoecology, 160(1-2), 153-163. doi:10.1016/s0031-0182(00)00063-8Mohabey, D. M. (1998). Systematics of Indian Upper Cretaceous dinosaur and chelonian eggshells. Journal of Vertebrate Paleontology, 18(2), 348-362. doi:10.1080/02724634.1998.10011063Moratalla JJ. 1993. Restos indirectos de dinosaurios del registro español: paleoicnología de la Cuenca de (Jurásico superior-Cretácico inferior) y paleoología del Cretácico superior [PhD dissertation]. Madrid: Universidad Autónoma de Madrid.Moreno-Azanza, M., Bauluz, B., Canudo, J. I., Gasca, J. M., & Torcida Fernández-Baldor, F. (2016). Combined Use of Electron and Light Microscopy Techniques Reveals False Secondary Shell Units in Megaloolithidae Eggshells. PLOS ONE, 11(5), e0153026. doi:10.1371/journal.pone.0153026Moreno-Azanza, M., Bauluz, B., Canudo, J. I., Puértolas-Pascual, E., & Sellés, A. G. (2013). A re-evaluation of aff. Megaloolithidae eggshell fragments from the uppermost Cretaceous of the Pyrenees and implications for crocodylomorph eggshell structure. Historical Biology, 26(2), 195-205. doi:10.1080/08912963.2013.786067Oms, O., Dinarès-Turell, J., Vicens, E., Estrada, R., Vila, B., Galobart, À., & Bravo, A. M. (2007). Integrated stratigraphy from the Vallcebre Basin (southeastern Pyrenees, Spain): New insights on the continental Cretaceous−Tertiary transition in southwest Europe. Palaeogeography, Palaeoclimatology, Palaeoecology, 255(1-2), 35-47. doi:10.1016/j.palaeo.2007.02.039Ortega, F., Bardet, N., Barroso-Barcenilla, F., Callapez, P. M., Cambra-Moo, O., Daviero- Gómez, V., … Sanz, J. L. (2015). The biota of the Upper Cretaceous site of «Lo Hueco» (Cuenca, Spain). Journal of Iberian Geology, 41(1). doi:10.5209/rev_jige.2015.v41.n1.48657Rasskin-Gutman, D., Elez, J., Esteve-Altava, B., & López-Martínez, N. (2020). Reconstruction of the internal structure of the pore system of a complex dinosaur eggshell (Megaloolithus siruguei). Spanish Journal of Palaeontology, 28(1), 61. doi:10.7203/sjp.28.1.17831Riera, V., Oms, O., Gaete, R., & Galobart, À. (2009). The end-Cretaceous dinosaur succession in Europe: The Tremp Basin record (Spain). Palaeogeography, Palaeoclimatology, Palaeoecology, 283(3-4), 160-171. doi:10.1016/j.palaeo.2009.09.018Sellés, A. G., Bravo, A. M., Delclòs, X., Colombo, F., Martí, X., Ortega-Blanco, J., … Galobart, À. (2013). Dinosaur eggs in the Upper Cretaceous of the Coll de Nargó area, Lleida Province, south-central Pyrenees, Spain: Oodiversity, biostratigraphy and their implications. Cretaceous Research, 40, 10-20. doi:10.1016/j.cretres.2012.05.004Tanaka, K., & Zelenitsky, D. K. (2014). Comparisons between experimental and morphometric water vapor conductance in the eggs of extant birds and crocodiles: implications for predicting nest type in dinosaurs. Canadian Journal of Zoology, 92(12), 1049-1058. doi:10.1139/cjz-2014-0078Vianey-Liaud, M., Khosla, A., & Garcia, G. (2003). Relationships between European and Indian dinosaur eggs and eggshells of the oofamily Megaloolithidae. Journal of Vertebrate Paleontology, 23(3), 575-585. doi:10.1671/0272-4634(2003)023[0575:rbeaid]2.0.co;2Vianey-Liaud, M., & Lopez-Martinez, N. (1997). Late Cretaceous dinosaur eggshells from the Tremp Basin, southern Pyrenees, Lleida, Spain. Journal of Paleontology, 71(6), 1157-1171. doi:10.1017/s002233600003609xVila, B., Galobart, À., Canudo, J. I., Le Loeuff, J., Dinarès-Turell, J., Riera, V., … Gaete, R. (2012). The diversity of sauropod dinosaurs and their first taxonomic succession from the latest Cretaceous of southwestern Europe: Clues to demise and extinction. Palaeogeography, Palaeoclimatology, Palaeoecology, 350-352, 19-38. doi:10.1016/j.palaeo.2012.06.008(2010). Lethaia, 43(2). doi:10.1111/let.2010.43.issue-2Vila, B., Jackson, F. D., Fortuny, J., Sellés, A. G., & Galobart, À. (2010). 3-D Modelling of Megaloolithid Clutches: Insights about Nest Construction and Dinosaur Behaviour. PLoS ONE, 5(5), e10362. doi:10.1371/journal.pone.0010362Vila, B., Riera, V., Bravo, A. M., Oms, O., Vicens, E., Estrada, R., & Galobart, À. (2011). The chronology of dinosaur oospecies in south-western Europe: Refinements from the Maastrichtian succession of the eastern Pyrenees. Cretaceous Research, 32(3), 378-386. doi:10.1016/j.cretres.2011.01.009Vila, B., Sellés, A. G., & Brusatte, S. L. (2016). Diversity and faunal changes in the latest Cretaceous dinosaur communities of southwestern Europe. Cretaceous Research, 57, 552-564. doi:10.1016/j.cretres.2015.07.003Vissers, R. L. M., & Meijer, P. T. (2012). Iberian plate kinematics and Alpine collision in the Pyrenees. Earth-Science Reviews, 114(1-2), 61-83. doi:10.1016/j.earscirev.2012.05.001Wright, V. P., & Platt, N. H. (1995). Seasonal wetland carbonate sequences and dynamic catenas: a re-appraisal of palustrine limestones. Sedimentary Geology, 99(2), 65-71. doi:10.1016/0037-0738(95)00080-

A high performance liquid chromatographic assay of Mefloquine in saliva after a single oral dose in healthy adult Africans

<p>Abstract</p> <p>Background</p> <p>Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT) recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva.</p> <p>Methods</p> <p>A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column.</p> <p>Results</p> <p>Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, <it>p </it>< 0.001). Saliva:plasma concentrations ratio was 0.42.</p> <p>Conclusion</p> <p>Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.</p

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

Background: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-alpha) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated. Methods: Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up. Results: Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17-159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50-1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91-1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1-23.9 vs. median, 7.35; range, 4.8-21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0-21.4 vs. median, 10.95; range, 8.0-32.6; P <.0005). In patients with follow-up of > 5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011). Conclusions: ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity

Vitrectomy with complete posterior hyaloid removal for ischemic central retinal vein occlusion: Series of cases

BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular disorder with potentially complications: (1) persistent macular edema and (2) neovascular glaucoma. No safe treatment exists that promotes the return of lost vision. Eyes with CRVO may be predisposed to vitreous degeneration. It has been suggested that if the vitreous remains attached to the macula owing to a firm vitreomacular adhesion, the resultant vitreous traction can cause inflammation with retinal capillary dilation, leakage and subsequent edema6. The roll of vitrectomy in ischemic CRVO surgical procedures has not been evaluated. CASE PRESENTATION: This is a non comparative, prospective, longitudinal, experimental and descriptive series of cases. Ten eyes with ischemic CRVO. Vitrectomy with complete posterior hyaloid removal was performed. VA, rubeosis, intraocular pressure (IOP), and macular edema were evaluated clinically. Multifocal ERG (m-ERG), fluorescein angiography (FAG) and optic coherence tomography (OCT) were performed. Follow-up was at least 6 months. Moderate improvement of visual acuity was observed in 60% eyes and stabilized in 40%. IOP changed from 15.7 ± 3.05 mmHg to 14.9 ± 2.69 mmHg post-operative and macular edema from 976 ± 196 μm to 640 ± 191 μm to six month. The P1 wave amplitude changed from 25.46 ± 12.4 mV to 20.54 ± 11.2 mV. CONCLUSION: A solo PPV with posterior hyaloid removal may help to improve anatomic and functional retina conditions in some cases. These results should be considered when analyzing other surgical maneuvers

Radiotherapy for Soft Tissue Sarcomas after Isolated Limb Perfusion and Surgical Resection: Essential for Local Control in All Patients?

Background: Standard treatment for localized soft tissue sarcoma (STS) is resection plus adjuvant radiotherapy (RTx). In approximately 10% of cases, resection would cause severe loss of function or even require amputation because of the extent of disease. Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan can achieve regression of the tumor, facilitating limb-saving resection. RTx improves local control but may lead to increased morbidity. Methods: In our database of over 500 ILPs, 122 patients with unifocal STS were treated by ILP followed by limb-sparing surgery. All included patients were candidates for amputation. Results: Surgery resulted in 69 R0 resections (57%), and in 53 specimens (43%) resection margins contained microscopic evidence of tumor (R1). Histopathological examination revealed >50% ILP-induced tumor necrosis in 59 cases (48%). RTx was administered in 73 patients (60%). Local recurrence rate was 21% after median follow-up of 31 months (2-182 months). Recurrence was significantly less in patients with >50% ILP-induced necrosis versus ≤50% necrosis (7% vs. 33%, P = 0.001). A similar significant correlation was observed for R0 versus R1 resections (15% vs. 28%, P = 0.04). In 36 patients with R0 resection and >50% necrosis, of whom 21 were spared RTx, no recurrences were observed during follow-up. Conclusions: In patients with locally advanced primary STS, treated with ILP followed by R0 resection, and with >50% ILP-induced necrosis in the resected specimen, RTx is of no further benefit

Developmental Expression of Kv Potassium Channels at the Axon Initial Segment of Cultured Hippocampal Neurons

Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation