Transcription of Leishmania major U2 small nuclear RNA gene is directed by extragenic sequences located within a tRNA-like and a tRNA-Ala gene

Sequence comparisons of U2 snRNA genes and flanking regions from T. cruzi (CL Brener Non-Esmeraldo-like). Sequences from the genes located on chromosomes 23, 37 and 6 are shown. The U2 snRNA gene from chromosome 23 is presented in blue font. The position of boxes A and B is indicated. Sequence numbers are relative to the TSS (+1) from the U2 snRNA. (PDF 1404 kb

Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3–4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.Supported in part with the grants PI10/01417 from Fondo de Investigaciones Sanitarias and RD12/0036/0029 from RTICC, Instituto de Salud Carlos III, 2014 SGR225(GRE), CERCA Program, Generalitat de Catalunya, Spain, and a funding from ‘La Caixa’ Foundation

Deployment of mating disruption dispensers before and after first seasonal male flights for the control of Aonidiella aurantii in citrus

The rejection of citrus fruit caused by infestations of the California red scale (CRS), Aonidiella aurantii (Maskell) (Hemiptera: Diaspididae), raises concerns about its management. This fact has led to the introduction of new integrated control methods in citrus orchards, including the implementation of techniques based on pheromones. Previous works described efficient mating disruption pheromone dispensers to control A. aurantii in the Mediterranean region. The main aims of the present study were to adjust the timing of dispenser applications and study the importance of controlling the early first generation of A. aurantii by testing two different application dates: before and after the first CRS male flight. The efficacy of the different mating disruption strategies was tested during 2010 in an experimental orchard and these results were confirmed during 2011 in a commercial citrus farm. Results showed that every mating disruption strategy achieved significantly lower male captures in monitoring pheromone traps compared with untreated plots, as well as mean fruit infestation reductions of about 80 %. The control of the first CRS generation is not essential for achieving a good efficacy as demonstrated in two locations with different pest pressure. The late application of MD dispensers before the second CRS male flight has proven to be effective, suggesting a new advantageous way to apply mating disruption.The authors want to thank Fernando Alfaro from Denia, Antonio Caballero, and Javier Macias from Rio Tinto Fruit S.A. (Huelva, Spain) for field support. We also thank Ecologia y Proteccion Agricola SL for the pheromone supply. This work has been funded by the Spanish Ministry of Science and Innovation (project AGL2009-10725) and Agroalimed Foundation. The translation of this paper was funded by the Universidad Politecnica de Valencia (Spain).Vacas González, S.; Alfaro Cañamás, C.; Primo Millo, J.; Navarro-Llopis, V. (2015). Deployment of mating disruption dispensers before and after first seasonal male flights for the control of Aonidiella aurantii in citrus. Journal of Pest Science. 88(2):321-329. https://doi.org/10.1007/s10340-014-0623-1S321329882Avidov Z, Balshin M, Gerson U (1970) Studies on Aphytis coheni, a parasite of the California red scale, Aonidiella aurantii in Israel. Biocontrol 15:191–207Barzakay I, Hefetz A, Sternlicht M, Peleg BA, Gokkes M, Singer G, Geffen D, Kronenberg S (1986) Further field trials on management of the California red scale, Aonidiella aurantii, by mating disruption with its sex-pheromone. Phytoparasitica 14:160–161Bedford ECG (1996) Problems which we face in bringing red scale, Aonidiella aurantii (Maskell), under biological control in citrus in South Africa. Proc Int Soc Citriculture 1:485–492Campos-Rivela JM, Martínez-Ferrer MT, Fibla-Queralt JM (2012) Population dynamics and seasonal trend of California red scale (Aonidiella aurantii Maskell) in citrus in Northern Spain. Span J Agric Res 10:198–208Collins PJ, Lambkin TM, Bodnaruk P (1994) Suspected resistance to methidation in Aonidiella aurantii (Maskell) (Homoptera: diaspididae) from Queensland. J Aust Entomol Soc 33:325–326Corma A, Muñoz-Pallares J, Primo-Yufera E (1999) Production of semiochemical emitters having a controlled emission speed which are based on inorganic molecular sieves. World Patent WO9944420Corma A, Muñoz-Pallares J, Primo-Yufera E (2000) Emitter of semiochemical substances supported on a sepiolite, preparation process and applications. World Patent WO0002448DeBach P (1959) New species and strains of Aphytis (Hymenoptera: Eulophidae) parasitic on the California red scale, Aonidiella aurantii (Mask.), in the Orient. Ann Entomol Soc Am 52:354–362DeBach P, Argyriou L (1967) The colonization and success in Greece of some imported Aphytis spp. (Hymenoptera: Aphelinidae) parasitic on citrus scale insects (Homoptera: Diaspididae). Biocontrol 12:325–342Desneux N, Decourtye A, Delpuech JM (2007) The sublethal effects of pesticides on beneficial arthropods. Ann Rev Entomol 52:81–106Diari Oficial de la Comunitat Valenciana (DOCV) (2008) DOCV no. 5901, 26. Resolution 27 October 2008 of Consellería de Agricultura, Pesca y Alimentación; November 2008. http://www.docv.gva.es/datos/2008/11/26/pdf/2008_13692.pdfDomínguez-Ruiz J, Sanchis J, Navarro-Llopis V, Primo J (2008) A new long-life trimedlure dispenser for Mediterranean fruit fly. J Econ Entomol 101:1325–1330Eliahu M, Blumberg D, Horowitz AR, Ishaaya I (2007) Effect of pyriproxyfen on developing stages and embryogenesis of California red scale (CRS), Aonidiella aurantii. Pest Manag Sci 63:743–746Furness G, Buchanan G, George R, Richardson N (1983) A history of the biological and integrated control of red scale, Aonidiella aurantii on citrus in the lower Murray Valley of Australia. Biocontrol 28:99–212Grafton-Cardwell EE, Gu P (2003) Conserving vedalia beetle, Rodolia cardinalis (Mulsant) (Coleoptera : Coccinellidae), in citrus: a continuing challenge as new insecticides gain registration. J Econ Entomol 96:1388–1398Grafton-Cardwell EE, Reagan CA (1995) Selective use of insecticides for control of armored scale (Homoptera: Diaspididae) in San-Joaquin Valley California citrus. J Econ Entomol 88:1717–1725Grafton-Cardwell EE, Vehrs SLC (1995) Monitoring for organophosphate-resistant and carbamate-resistant armored scale (Homoptera: Diaspididae) in San-Joaquin Valley citrus. J Econ Entomol 88:495–504Grafton-Cardwell EE, Lee JE, Stewart JR, Olsen KD (2006) Role of two insect growth regulators in integrated pest management of citrus scales. J Econ Entomol 99:733–744Grout TG, Richards GI (1991a) Effect of buprofezin applications at different phenological times on California red scale (Homoptera: Diaspididae). J Econ Entomol 84:1802–1805Grout TG, Richards GI (1991b) Value of pheromone traps for predicting infestations of red scale, Aonidiella aurantii (Maskell) (Homoptera: Diaspididae), limited by natural enemy activity and insecticides used to control citrus thrips, Scirtothrips aurantii Faure (Thysanoptera: Thripidae). J Appl Entomol 111:20–27Grout TG, Du Toit WJ, Hofmeyr JH, Richards GI (1989) California red scale (Homoptera: Diaspididae) phenology on citrus in South Africa. J Econ Entomol 82:793–798Hefetz A, Kronengerg S, Peleg BA, Bar-zakay I (1988) Mating disruption of the California red scale Aonidiella aurantii (Homoptera: Diaspididae). In: Proceeding 6th International Citrus Congress, Tel Aviv (Israel), pp 1121–1127Hernández-Penadés P, Rodríguez-Reina JM, García-Marí F (2002) Umbrales de tratamiento para cóccidos diaspídidos en cítricos. Bol San Veg Plagas 28:469–478Hothorn T, Bretz F, Westfall P (2008) Simultaneous Inference in General Parametric Models. Biometrical J 50:346–363Ioratti C, Anfora G, Tasin M, De Cristofaro A, Witzgall P, Lucchi A (2011) Chemical ecology and management of Lobesia botrana (Lepidoptera: Tortricidae). J Econ Entomol 104:1125–1137Kehat M, Anshelevich L, Harel M, Dunkelblum E (1995) Control of the codling moth (Cydia pomonella) in apple and pear orchards in Israel by mating disruption. Phytoparasitica 23:285–296Kennett CE, Hoffmann RW (1985) Seasonal development of the California red scale (Homoptera: Diaspididae) in San Joaquin Valley citrus based on degree-day accumulation. J Econ Entomol 78:73–79Levitin E, Cohen E (1998) The involvement of acetylcholinesterase in resistance of the California red scale shape Aonidiella aurantii to organophosphorus pesticides. Entomol Exp Appl 88:115–121Lykouressis D, Perdikis D, Samartzis D, Fantinou A, Toutouzas S (2005) Management of the pink bollworm Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae) by mating disruption in cotton fields. Crop Prot 24:177–183McLaren IW, Buchanan GA (1973) Parasitism by Aphytis chrysomphali Mercet and A. melinus Debach of Californian red scale, Aonidiella aurantii (Maskell), in relation to seasonal availability of suitable stages of the scale. Austr J Zool 21:111–117Moreno DS, Kennett CE (1985) Predictive year-end California red scale (Homoptera: Diaspididae) orange fruit infestations based on catches of males in the San-Joaquin Valley. J Econ Entomol 78:1–9Moreno DS, Luck RF (1992) Augmentative releases of Aphytis melinus (Hymenoptera: Aphelinidae) to suppress California red scale (Homoptera: Diaspididae) in southern California lemon orchards. J Econ Entomol 85:1112–1119Pekas A, Aguilar A, Tena A, García-Marí F (2010) Influence of host size on parasitism by Aphytis chrysomphali and A. melinus (Hymenoptera: Aphelinidae) in Mediterranean populations of California red scale Aonidiella aurantii (Hemiptera: Diaspididae). Biol Control 55:132–140Rill S, Grafton-Cardwell EE, Morse JG (2007) Effects of pyriproxyfen on California red scale (Hemiptera: Diaspididae) development and reproduction. J Econ Entomol 100:1435–1443Rodrigo E, Troncho P, García-Marí F (1996) Parasitoids (Hymenoptera: Aphelinidae) of three scale insects (Homoptera: Diaspididae) in a citrus grove in Valencia, Spain. Entomophaga 41:77–94Roelofs WL, Gieselmann MJ, Cardé AM, Tashiro H, Moreno DS, Henrick CA, Anderson RJ (1977) Sex-pheromone of California red scale, Aonidiella aurantii. Nature 26:698–699Rongai D, Cerato C, Lazzeri L, Palmieri S, Patalano G (2008) Vegetable oil formulation as biopesticide to control California red scale (Aonidiella aurantii Maskell). J Pest Sci 81:179–185Sorribas JJ, Rodríguez R, Rodrigo E, García-Marí F (2008) Niveles de parasitismo y especies de parasitoides del piojo rojo de california Aonidiella aurantii (Hemiptera: Diaspididae) en cítricos de la Comunidad Valenciana. Bol San Veg Plagas 34:201–210Sorribas J, van Baaren J, Garcia-Marí F (2012) Effects of climate on the introduction, distribution and biotic potential of parasitoids: applications to biological control of California red scale. Biol Control 62:103–112Staten RT, Flint HM, Weddle RC, Quintero E, Zarate RE, Finell CM, Hernandes M, Yamamoto A (1987) Pink bollworm (Lepidoptera: Gelechiidae): large-scale field trials with a high-rate gossyplure formulation. J Econ Entomol 80:1267–1271Tashiro H, Chambers DL (1967) Reproduction in the California Red Scale, Aonidiella aurantii (Homoptera: Diaspididae). I. Discovery and extraction of a female sex pheromone. Ann Entomol Soc Am 60:1166–1170Tena A, Llácer E, Urbaneja A (2013) Biological control of a non-honeydew producer mediated by a distinct hierarchy of honeydew quality. Biol Control 67:117–122University of California (1991) Integrated pest management for citrus. University of California, BerkeleyVacas S, Alfaro C, Navarro-Llopis V, Primo J (2009) The first account of the mating disruption technique for the control of California red scale Aonidiella aurantii Maskell (Homoptera: Diaspididae) using new biodegradable dispensers. Bull Entomol Res 99:415–423Vacas S, Alfaro C, Navarro-Llopis V, Primo J (2010) Mating disruption of California red scale, Aonidiella aurantii Maskell (Homoptera: Diaspididae), using biodegradable mesoporous pheromone dispensers. Pest Manag Sci 66:745–751Vacas S, Vanaclocha P, Alfaro C, Primo J, Verdú MJ, Urbaneja A, Navarro-Llopis V (2011) Mating disruption for the control of Aonidiella aurantii Maskell (Hemiptera: Diaspididae) may contribute to increased effectiveness of natural enemies. Pest Manag Sci 68:142–148Vanaclocha P, Vacas S, Alfaro C, Primo J, Verdú MJ, Navarro-Llopis V, Urbaneja A (2012) Life history parameters and scale-cover surface area of Aonidiella aurantii are altered in a mating disruption environment: implications for biological control. 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Biodiversidad regional: Santa María, Boyacá. Guía de Campo. Artrópodos, arácnidos, miriápodos, crustáceos, insectos.

ilustraciones, fotografías mapasEs un gran orgullo y satisfacción poder continuar con la presentación a la comunidad científica y académica en general, y en forma muy particular, a todos aquellos que viven y disfrutan de la enorme diversidad biológica de la Región de Santa María, Boyacá, la quinta guía de campo: “Biodiversidad regional, Santa María, Boyacá. Guía de Campo: Artrópodos”, en la cual uno de los más destacados entomólogos del país, el profesor Germán Amat García del Instituto de Ciencias, actúa como editor de la contribución. Para ello, concibió la idea de invitar a varios reconocidos especialistas nacionales para que proyectaran su experiencia y conocimiento a disposición y servicio de esta interesante empresa. La experiencia de estos destacados estudiosos del mundo de los artrópodos se visualiza en este nuevo libro que llega al público en general y les muestra otro ámbito de las enormes riquezas biológicas que guarda la región de Santa María, como es la relacionada con el inconmensurable mun- do de los organismos animales presentes en la zona. (texto tomado de la fuente)PRESENTACIÓN AES CHIVOR -- PRESENTACIÓN ICN -- AGRADECIMIENTOS -- DIRECTORIO DE AUTORES -- INTRODUCCIÓN -- LA REGIÓN DE SANTA MARÍA -- LOCALIZACIÓN Y COMPONENTES DEL PAISAJE -- CARACTERIZACIÓN DE HÁBITATS Y SITIOS DE VISITA -- LOS ARTRÓPODOS: MODELOS DE LA BIODIVERSIDAD -- CONOCIMIENTO, USO Y CONSERVACIÓN DE ARTROPODOS -- POR QUÉ SE EXTINGUEN LOS ARTRÓPODOS? -- LOS ARTRÓPODOS DE SANTA MARÍA -- ESTRUCTURA TEMÁTICA DE ESTA GUÍA -- LISTA DE AUTORES DE FOTOGRAFÍAS -- ARAÑAS -- ESCORPIONES -- OPILIONES -- PSEUDOESCORPIONES -- UROPYGIDOS -- AMBLYPÍGIDOS -- ESQUIZÓMIDOS -- RICINULÉIDOS -- 70 MIRIÁPODOS -- CANGREJOS -- LIBÉLULAS -- GRILLOS, LANGOSTAS, SALTAMONTES -- MÁNTIDOS --TERMES -- HEMÍPTEROS -- ESCARABAJOS -- ESCARABAJOS CARROÑEROS -- ESCARABAJOS ERRANTES .-- ESCARABAJOS TÍPICOS -- ESCARABAJOS CANTHAROIDEOS -- ESCARABAJOS LONGICORNIOS -- ESCARABAJOS DE LAS HOJAS -- HORMIGAS -- AVISPAS -- ABEJAS Y ABEJORROS -- MOSCAS .-- POLILLAS -- GLOSARIO -- ÍNDICE ALFABÉTICO GENERAL DE FAMILIAS Y GÉNEROS -- BIBLIOGRAFÍAPrimera edició

Babassu aqueous extract (BAE) as an adjuvant for T helper (Th)1-dependent immune responses in mice of a Th2 immune response-prone strain

<p>Abstract</p> <p>Background</p> <p>The aqueous extract of a Brazilian palm-tree fruit - the babassu - (BAE) exerts a clear immunostimulative activity <it>in vivo</it>. In the present work, the possibility that BAE can promote Th1 immune responses in mice of a Th2 immune response-prone strain - the BALB/c was investigated. BAE itself, and preparations consisting of <it>Leishmania amazonensis </it>promastigote extract (LE), adsorbed or not to Al(OH)₃, and in the presence or not of BAE, were used as immunogens. LE and Al(OH)₃have been shown to preferentially elicit Th2 immune responses.</p> <p>Results</p> <p>The addition of BAE to LE-containing immunogenic preparations, adsorbed or not to Al(OH)₃, clearly promoted the <it>in vitro </it>production of interferon γ (IFN-γ), a major Th1-dependent cytokine, and not of interleukin (IL-)4 (a Th2-dependent cytokine), by LE-stimulated splenocytes of immunized BALB/c mice. It also promoted the <it>in vivo </it>formation of IgG2a anti-LE antibodies. However, immunization with LE by itself led to an increased production of IL-4 by LE-stimulated splenocytes, and this production, albeit not enhanced, was not reduced by the addition of BAE to the immunogen. On the other hand, the IL-4 production by LE-stimulated splenocytes was significantly lower in mice immunized with a preparation containing Al(OH)₃-adsorbed LE and BAE than in mice immunized with the control preparation of Al(OH)₃-adsorbed LE without BAE. Moreover, an increased production of IFN-γ, and not of IL-4, was observed in the culture supernatants of splenocytes, from BAE-immunized mice, which were <it>in vitro </it>stimulated with BAE or which received no specific <it>in vitro </it>stimulus. No differences in IL-10 (an immunoregulatory cytokine) levels in the supernatants of splenocytes from mice that were injected with BAE, in relation to splenocytes from control mice, were observed. The spontaneous <it>ex vivo </it>production of NO by splenocytes of mice that had been injected with BAE was significantly higher than the production of NO by splenocytes of control mice.</p> <p>Conclusions</p> <p>Based on the results described above, BAE, or biologically active molecules purified from it, should be further investigated as a possible adjuvant, in association or not with aluminium compounds, for the preferential induction of Th1-dependent immune responses against different antigens in distinct murine strains and animal species.</p

Salud de los trabajadores

Actividad f&iacute;sica y su relaci&oacute;n con los factores de riesgo cardiovascular de carteros chilenosAn&aacute;lisis de resultados: riesgos psicosociales en el trabajo Suceso-Istas 21 en Cesfam Quell&oacute;nAusentismo laboral por enfermedades oftalmol&oacute;gicas, Chile 2009Brote de diarreas por norovirus, posterremoto-tsunami, Constituci&oacute;n, Regi&oacute;n del MauleCalidad de vida en profesionales de la salud p&uacute;blica chilenaCaracterizaci&oacute;n del reposo laboral en personal del SSMN durante el primer semestre de 2010Concentraci&oacute;n de nicotina en pelo en trabajadores no fumadores expuestos a humo de tabaco ambientalCondiciones de trabajo y bienestar/malestar docente en profesores de ense&ntilde;anza media de SantiagoDisfunci&oacute;n auditiva inducida por exposici&oacute;n a xilenoErgonom&iacute;a aplicada al estudio del s&iacute;ndrome de dolor lumbar en el trabajoEstimaci&oacute;n de la frecuencia de factores de riesgo cardiovascular en trabajadores de una empresa mineraExposici&oacute;n a plaguicidas inhibidores de la acetilcolinesterasa en Colombia, 2006-2009Factores de riesgo y da&ntilde;os de salud en conductores de una empresa peruana de transporte terrestre, 2009Las consecuencias de la cultura en salud y seguridad ocupacional en una empresa mineraPercepci&oacute;n de cambios en la pr&aacute;ctica m&eacute;dica y estrategias de afrontamientoPercepci&oacute;n de la calidad de vida en la Universidad del Biob&iacute;oPesos m&aacute;ximos aceptables para tareas de levantamiento manual de carga en poblaci&oacute;n laboral femeninaRiesgo coronario en trabajadores mineros seg&uacute;n la funci&oacute;n de Framingham adaptada para la poblaci&oacute;n chilenaTrastornos emocionales y riesgo cardiovascular en trabajadores de la salu

Demographic History of Indigenous Populations in Mesoamerica Based on mtDNA Sequence Data

The genetic characterization of Native American groups provides insights into their history and demographic events. We sequenced the mitochondrial D-loop region (control region) of 520 samples from eight Mexican indigenous groups. In addition to an analysis of the genetic diversity, structure and genetic relationship between 28 Native American populations, we applied Bayesian skyline methodology for a deeper insight into the history of Mesoamerica. AMOVA tests applying cultural, linguistic and geographic criteria were performed. MDS plots showed a central cluster of Oaxaca and Maya populations, whereas those from the North and West were located on the periphery. Demographic reconstruction indicates higher values of the effective number of breeding females (Nef) in Central Mesoamerica during the Preclassic period, whereas this pattern moves toward the Classic period for groups in the North and West. Conversely, Nef minimum values are distributed either in the Lithic period (i.e. founder effects) or in recent periods (i.e. population declines). The Mesomerican regions showed differences in population fluctuation as indicated by the maximum Inter-Generational Rate (IGRmax): i) Center-South from the lithic period until the Preclassic; ii) West from the beginning of the Preclassic period until early Classic; iii) North characterized by a wide range of temporal variation from the Lithic to the Preclassic. Our findings are consistent with the genetic variations observed between central, South and Southeast Mesoamerica and the North-West region that are related to differences in genetic drift, structure, and temporal survival strategies (agriculture versus hunter-gathering, respectively). Interestingly, although the European contact had a major negative demographic impact, we detect a previous decline in Mesoamerica that had begun a few hundred years before

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis