Clinical Features And Laboratory Patterns In A Cohort Of Consecutive Argentinian Patients With Von Willebrand's Disease

Background and Objectives. von Willebrand's disease (vWD) is a bleeding disorder with variable clinical expression. Our aim was to classify patients with vWD and to determine the phenotype in their relatives. Design and Methods. The types and subtypes, blood group frequency and its relevance, bleeding sites, response to the desmopressin (DDAVP) test, transfusion requirements and clinical features in type 1 and 2A families were determined in 1,885 patients. Results. Our findings were: type 1: 91%, type 2A: 3.1%, severe vWD: 1.3%; type 2N: 1.6%; type low intraplatelet: 2.7%; combined 1+2N: 0.3%. Blood group O prevalence was 70.5%. Bleeding and transfusion requirements were not correlated to blood groups. The most frequent symptoms were: ecchymoses-hematomas and epistaxis and, in females over 13 years, also menorrhagia. Normal levels of factor VIII:C were found in 38.4% of the patients. DDAVP was infused in 567 patients with a good response in 80.6%. About 9% of our patients needed transfusion therapy. The diagnosis of von Willebrand’s disease is more likely in subjects belonging to families with type 2A disease than in members of families with type 1 vWD in spite of these being symptomatic. Interpretation and Conclusions. These observations provide a good strategy to identify, classify and treat vWD patients without performing molecular assays.Fil: Woods, Adriana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Meschengieser, S. S.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Blanco, A. N.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Salviu, M. J.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Farias, Cristina Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Kempfer, Ana Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentin

Monitoring of ivermectin residues in bovine and pork tissues

Argentina is traditionally a beef-producing country. However, in recent years other productions have grown exponentially. Due to improvements in technology, changes in customs, or economic issues, consumer preferences have changed for cheaper meats. Animal production systems, both extensive and intensive, are closely linked to veterinary drug use for prevention, control, or treatment of parasitic diseases. Consequently, if good agricultural practices are not respected, products obtained from these productions could present residues above the Maximum Residue Limits (MRLs). In this context, ivermectin (IVM), an endectocide drug belonging to the macrocyclic lactone group, is one of the most widely used to treat parasitic diseases. IVM residues above the MRLs in bovine and pork tissues may constitute a risk to consumer health. Consequently, the current study aimed to assess the presence of ivermectin residues in bovine and pork tissues for local consumption in Buenos Aires province (Argentina). Samples of bovine/pork meat and fat, and bovine liver and kidney were taken for 3 years during the winter and summer seasons in 5 cities of Buenos Aires province. Tissue samples were analyzed by HPLC with a fluorescence detector. Of a total of 691 samples analyzed, 87 of them presented residues of IVM. However, only 13 samples from the positive ones showed concentrations above the Codex MRL. Mean IVM concentrations (range) were 42.18 (0.11?587.15), 31.66 (2.96?283.33), 162.61 (1.32?516.55), 22.78 (1.51?65.40), 15.26 (0.07?194.25) and 22.14 (1.58?126.76) ppb for bovine meat, bovine fat, bovine liver, bovine kidney, pork meat, and pork fat, respectively. In conclusion, bovine and pork tissue ingestion is safe for the consumer. However, 1.88% of the samples showed IVM concentrations above de MRL, thus the implementation of residue surveillance programs at the local level guaranteeing consumer health is strongly recommended.Fil: Cantón, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Cantón, Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Dominguez, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Farias, Cristina Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina67th Annual Meeting American Association of Veterinary ParasitologistsSnowbirdEstados UnidosAmerican Association of Veterinary Parasitologist

Impact of extra-label use of albendazole and fipronil in poultry

The increase of argentine poultry production in the last years is closely linked by the use of antiparasitic drugs in order to optimize this production, being the compounds available scarce. Albendazole (ABZ) and fipronil (FIP) are used extra-label for the control of nematode and external parasites, respectively. The goals of the study were: a) to evaluate the ABZ egg residues and its effect on the fertility and hatchability (Study-A); b) to investigate the FIP egg residues profiles after its extra-label administration to laying-hens (Study-B). Study-A: Forty eight (48) breeder hens were randomly divided into four groups and treated with ABZ at either 10, 40 or 80 mg/kg/day in feed over seven days, an untreated group was used as Control. Eggs were incubated under controlled conditions and fertility and hatchability were assessed. Study-B: Hens from a local farm were extralabel treated with FIP in feed. Eggs were collected for a 36 days post-treatment period. In Study-A, while fertility was not affected by ABZ, the hatchability values decreased inversely with the administered ABZ dose level. A statistically significant (P<0.05) reduction on egg hatchability was observed with ABZ treatment at the highest doses (40 and 80 mg/kg/day). In Study-B, residue concentrations of fipronil-sulfone (active metabolite of FIP) were found in yolk egg at higher levels than the Maximum Residue Limits (MRL) allowed. Altogether, these data strongly suggest that extra-label use of ABZ and FIP would generate a high level risk on consumers as well as on poultry production.Fil: Cantón, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Dominguez, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Farias, Cristina Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Moreno Torrejon, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina26° International Conference of the World Association for the Advancement of Veterinary ParasitologyKuala LumpurMalasiaWorld Association for the Advancement of Veterinary Parasitolog

Contrasting molluscan fauna collected with beam trawl and otter trawl in circalittoral and bathyal soft bottoms of the northern Alboran Sea

The Alboran Sea display complex oceanographic, geological, ecological and biological processes, promoting a high biodiversity and complexity (Robles, 2010). On the other hand, molluscs constitute one of the most diverse and best represented invertebrate groups in this area, representing an important component of soft bottom communities, as well as the second group in abundance and biomass in demersal fisheries, with species of ecological and commercial importance worldwide (Gofas et all., 2011). The study of the molluscan assemblages is important where trawling fishing fleets operate, in order to improve fisheries assessment and move forward to an ecosystem based approach, which takes into account other components of the fishery than the target species such as non-target and protected species and habitats (Pikitch et al., 2004). Information collected on fisheries assemblages may introduce a bias depending on the fraction of the assemblage (e.g. demersal, epifaunal, infaunal) at which the sampling method is targeted, particularly in a group such as molluscs with a high variability in life strategies. The aims of this study are 1) to increase the scarce knowledge on the composition and structure of molluscan assemblages of circalittoral and bathyal soft bottoms of the Alboran Sea; and 2) to compare the information obtained on these assemblages by using two different types of sampling gears, the beam trawl and the otter trawl. During the MEDITS trawl surveys (springs 2014 and 2015) a beam trawl (BT) (horizontal opening 1.3 x vertical opening 1.2 m, mesh size 10 mm) and an otter trawl (OT)(GOC 73) (2.5 x 21.5 m , mesh size 20 mm) were used in 35 sampling stations at depths from 40 to 800 m in the Alboran Sea. Catches were sorted to species and their individuals counted and weighed. The molluscan assemblages and species were characterized according to their dominance (%Da) and frequency of occurrence (%F). Multivariate analyses using the Bray-Curtis index were performed with presence/absence species data and quantitative data obtained with each method were standardized to a similar sampling area. ANOSIM was used for testing the differences between groups of samples according to different factors (depth and sampling type) and SIMPER for the contribution of the different species to these factors using PRIMER v6. The characterization of the different types of sampling and assemblages was done with the species richness and statistical differences tested with Kruskal-Wallis using SPSS software. A total of 170 spp. have been collected, with 69 species collected in OT samples, mostly cephalopods (26 spp., 37.68%), followed by gastropods (25 spp., 36.23%) and bivalves (18 species, 26.10% total species of OT), being the latter the most abundant group. The top-dominant species were the bivalve Neopycnodonte cochlear and the cephalopod Alloteuthis media, whereas the most frequent ones were the cephalopods Octopus vulgaris, Todarodes sagittatus and Illex coindetii (Fig. 1 ). In beam trawl samples, 135 spp. of 6 classes were found, being gastropods the most diverse and abundant one (69 spp., 51.11% total species of BT), followed by bivalves (49 spp., 36.3%) and cephalopods (15 spp., 11.11%). The top-dominant species were the gastropods Turritella communis and Nassarius ovoideus and the bivalves Nucula sulcata and Abra longicallus, and the most frequent ones included Nucula sulcata, Nassarius ovoideus and the gastropod Euspira fusca (Figure 1). Contrasting both methods, only 20% (34 spp.) of the species were exclusively collected in OT samples (e.g. Alloteuthis spp., I. coindetii, Loligo spp., T. sagittatus) and 57% (97 spp.) in BT samples (e.g. N. ovoideus, Timoclea ovata, N. sulcata, Clelandella miliaris). Only 23% of the species (39 spp.) were collected with both methods (e.g. Venus nux, Turritella communis, N. cochlear). Figure 1. Some common and dominant mollusc of beam trawl (A-C, E-G) and otter trawl samples (D, H-J) collected in circalittoral and bathyal soft bottoms of the northern Alboran Sea. A) Turritella communis; B) Abra longicallus; C) Nassarius ovoideus; D) Illex coindeitii; E) Clelandella miliaris; F) Timoclea ovata; G) Nucula sulcata; H) Venus nux; I) Octopus vulgaris; J) Neopycnodonte cochlear. Multivariate analyses clearly separated two groups of samples, each one collected with a different sampling method, and in each grouping it revealed three main mollusks assemblages in relation to depth: I) Continental shelf (CS) (40-200 m), II) Upper slope (UCS) (201-400 m), and III) and Middle slope (MCS) (400-1800 m) (Fig. 2). Figure 2. MDS applied to presence-absence data of molluscs assemblages obtained from beam trawl and otter trawl samples collected in the northern Alboran Sea. BT: Beam trawl; OT: Otter trawl ; CS: Continental Shelf; UCS: Upper Continental Slope; MCS: Middle Continental Slope. The continental shelf assemblage in BT samples were characterized by T. ovata, N. cochlear, N. ovoideus and T. communis, whereas O. vulgaris, Eledone moschata and I. coindetii characterized the OT samples. For the upper and middle slope assemblages, E. fusca and A. longicallus characterized the BT samples, whereas T. sagittatus and Bathypolypus sponsalis characterized the OT samples. Mean values of species richness were significantly higher when using the BT. This study showed that OT nor BT samples can provide complete information on the whole molluscan assemblage, giving each sampling method complimentary information. The demersal and epi-benthic fractions of the community were better sampled using the otter trawl and the beam trawl, respectively. The estimates of infauna were higher using the beam trawl, but this information should be contrasted with data obtained from dredges in order to assess whether the beam trawl yield acceptable estimates of the abundance of these molluscs

Preliminary characterization of echinoderm assemblages in circalittoral and bathyal soft bottoms of the northern Alboran Sea

Echinoderms, with 7.272 species described so far (based on WORMS), provide an ecosystemic role which can be important depending on their habitat, and including tag species (Manjón-Cabeza et al., 2014; Palma-Sevilla 2015) or even dominant ones (Iken et al., 2010; Hughes et al., 2012). Despite the increasing knowledge on their taxonomy, studies on ecological and assemblage composition and structure of echinoderms are very scarce compared to those for other invertebrate groups, being this information essential for improving the knowledge on Mediterranean ecosystems (Coll et al., 2010). The Alboran Sea, in the junction of the Atlantic Ocean and the Mediterranean Sea and the European and African continental margins, represents a biodiversity hotspot due to the overlapping of species from those basins and continents, including some endemic components (Coll et al., 2010). Regarding echinoderms of the Alboran Sea, most previous studies focussed on infralittoral bottoms, with very few for circalittoral and bathyal ones (Manjón-Cabeza et al, 2014; Sibuet, 1974). Nevertheless, these studies generally included faunistic lists (Ocaña & Pérez-Ruzafa, 2004; Manjón-Cabeza et al., 2014), sometimes with identification keys, ecological and distributional data of some species and rarely on the assemblage composition and structure (Palma-Sevilla, 2015), which represent the main aim of this study on echinoderm assemblages of circalittoral and bathyal soft bottoms of the Alboran Sea. During the MEDITS survey expeditions (April-May 2014-2015) on board the R/V Miguel Oliver (Fig. 1), 35 samples were collected using a beam trawl (horizontal and vertical openings of 1.3 and 1.2 m, respectively, and a mesh size of 10 mm in the codend) at depths from 40 to 774 m in the Alboran Sea (Fig. 1). Hauls were done at a speed of ca. 2 knots during 5-10 (shelf stations) and 15 minutes (slope stations). Echinoderms were separated, identified to the lowest possible taxonomic leveland specimens counted and weighed to the nearest 0.5 g. Abundance and biomass data were standardized to 1000 m2 according to the sampling area of each haul. Echinoderm assemblages were characterized according to the dominance and frequency of occurrence of species in the samples and considering different ecological indexes. Multivariate methods (CLUSTER, nMDS, SIMPER, ANOSIM) were applied, based on the Bray & Curtis similarity index, for detecting and contrastingassemblages in relation to depth and 4 geographic areas of the Alboran Sea with different influence of Atlantic waters (Occidental-Esteponato Málaga, Central-Málaga to Motril, Oriental-Motril to Almería and Alboran Island). Fig. 1. Location of beam-trawl samples (dots) collected during 2014 and 2015 MEDITS expeditions in the northern Alboran Sea. At present 39 taxa have been detected, mostly belonging to Ophiuroidea and Asteroidea (28.2 and 25.6% of all species, respectively), followed by Holothuroidea (23.1%), Echinoidea (17.9%) and Crinoidea (5.1%). Regarding abundance, a total of 54689 individuals have been collected, being Ophiuroidea (98.6% of all individuals), Holothuroidea (0.6%) and Crinoidea (0.4%) the top-dominant classes. Regarding biomass, ophiuroids also dominated (52.8%), followed by asteroids (16.1%) and holothuroids (15.0%). Considering other faunistic groups, echinoderms were the most abundant phyllum in the samples (60.7%) and the fifth one in biomass (7.6%). The dominant (for both abundance and biomass) and frequent genera included Ophiocten (displaying dominances >90%) Hymenodiscus, Luidia and Astropecten for asteroids, Antedon and Leptometra for crinoids, Dendrochirotida and Molpadidae for holothuroids, and Brissopsis and Echinocyamus for echinoids (Fig. 2). Fig. 2. Some echinodermscollected in circalittoral and bathyal soft bottoms of the Alboran Sea using beam-trawl during the MEDITS expeditions. A: Ophiocten; B: Dendrochirotida sp.; C: Brissopsis; D: Anseropoda; E: Luidia. Multivariate analyses indicated groupings of samples and significantly different echinoderm assemblages in relation to depth (RANOSIM=0.22, p0.05). Shelf assemblages displayed lower intra-group similarities (<20% similarity in SIMPER) than the slope ones (ca. 40%). Species characterizing the shelf assemblages belonged to the genera Astropecten, Antedon, Ophiothrix among others, whereas those of the slope belonged to the genera Luidia (L. sarsi), Hymenodiscus, Ophiocten, Leptometra and Amphiura

Asociaciones de moluscos de fondos sedimentarios circalitorales y batiales del norte del mar de Alborán

Molluscan assemblages from shelf and slope soft bottoms of the Alboran Sea have been sampled with a beam trawl during 2014 and 2015 MEDITS expeditions. A total of 134 spp. of molluscs (shell size > 3 mm) were identified, being gastropods the most diverse and dominant group. Four main depth related assemblages were detected in multivariate analyses and characterized by (1) Turritella communis, Chamelea striatula and Nucula sulcata for the inner shelf, (2) Timoclea ovata, Clelandella miliaris and Neopycnodonte cochlear for the outer shelf, (3) Nassarius ovoideus, Calumbonella suturale and N. sulcata for the upper slope and (4) Abra longicallus, Euspira fusca and Aporrhais serresianus for the middle slope. Species richness and abundance decreased with depth, unlike evenness and Shannon-Wiener diversity which displayed an opposite pattern. A higher spatial variability was detected for the shelf, indicating that more assemblages may occur at this level and further sampling is needed for covering all sedimentary habitat types of the Alboran Sea.Versión del edito

Detecção de desvios de qualidade nos medicamentos manipulados: solução de ácido acético, xarope de cetoconazol e cápsulas de hormônio tireoidiano T4

Introdução: Doses incorretas do ativo nas preparações magistrais configuram erros comuns na manipulação, podendo ocasionar agravos à saúde do paciente, refletindo possível ausência das Boas Práticas de Manipulação (BPM). Objetivo: Relatar desvios de qualidade nos medicamentos solução de ácido acético, xarope de cetoconazol e cápsulas de T4. Método: Identificação por reações químicas e por CLAE, teor por titulação e CLAE, pH por potenciometria. Resultados: Identificação positiva, para ácido acético com teor de 98,20% compatível com ácido acético glacial, em desacordo com a prescrição de solução a 5%. O teor de cetoconazol de 16,20 mg/mL encontrado no xarope corresponde a 81,00% do declarado, com especificação mínima de 90,00%; pH 8,0; identificação positiva para tensoativo aniônico componente saponáceo, no xarope. Os resultados encontrados: cápsulas de T4 de 25 μg foi de 177,70 μg e as de 200 μg foi de 174,44 μg, correspondendo a 710,96% e 87,22% do teor declarado, respectivamente, em desacordo com a especificação de 90,00% a 110,00%. Conclusões: O trabalho ilustrou a detecção de desvios de qualidade em medicamentos manipulados de diferentes farmácias, decorrentes de erros farmacotécnicos, ausência de controle de qualidade e falta de implementação das BPM. A frequente fiscalização previne riscos sanitários à população

Otimização e validação intralaboratorial de método analítico por CLAE/UV para identificação e quantificação de p-fenilenodiamina em tinturas de hena para cabelos e sobrancelhas

Introduction: p-Phenylenediamine (PPD), aromatic sensitizing amine, has been added to&nbsp; henna powder to modify its natural color to black, increasing its fixation time, a practice&nbsp; that is prohibited in eyelash and eyebrows dyes. Objective: The objective of this study was to optimize and validate, at an intra-laboratory level, an analytical method by HPLC/UV for identification and quantification of PPD in hen dyes for hair and eyebrows. Method: In the method, C8 reverse phase column, mobile phase 1% triethanolamine (pH 8.4) andacetonitrile (99: 1, v/v), detection 280nm, injection volume: 10uL, flow 1.0 mL/min, column temperature 32°C, run time 10 min, linearity 5-45 μg/mL (n = 5) with correlation coefficient 0.9982, were used. For Cochran test (homoscedasticity): 0.3350 and Critical (0.3934) with 99% confidence. Limits of detection 1.17 μg/mL and quantification 3.54 μg/mL. The coefficient of variation of repeatability was 0.12% and the intermediate precision by F-test yielded p value of 0.283 with 95% of confidence. Accuracy results comprised acceptance criteria of 90%-107%. Results: Of the 19 analyzed samples, 14 presented PPD content between 1.74 and 3.65% w/w, in disagreement with Legislation. Conclusions: The proposed method can contribute to monitoring of quality and safety of use of these products.Introdução: O p-fenilenodiamina (PPD), amina aromática sensibilizante, vem sendo adicionado ao pó de hena para modificar sua cor natural para preta, aumentando seu tempo de fixação, prática proibida em tinturas para cílios e sobrancelhas. Objetivo: O objetivo deste estudo foi otimizar e validar, em níveis intralaboratoriais, um método analítico por CLAE/UV para identificação e quantificação de PPD em tinturas de hena para cabelos e sobrancelhas. Método: Foi utilizada coluna em fase reversa C8, fase móvel trietanolamina 1% (pH 8,4) e acetonitrila (99:1, v/v), detecção a 280 nm, volume de injeção de 10 μL, fluxo 1,0 mL/min, temperatura da coluna32°C, tempo de corrida 10 min, linearidade 5-45 μg/mL (n = 5) com coeficiente de correlação de 0,9982. Para o teste de Cochran (homocedasticidade), 0,3350 e o Ccrítico (0,3934), com 99% de confiança. Limites de detecção, 1,17 μg/mL e quantificação, 3,54 μg/mL. O coeficiente de variação da repetibilidade 0,12% e na precisão intermediária pelo teste F obteve-se p-valor de 0,283 com 95% de confiança. Resultados: Os resultados da exatidão compreenderam os critérios de aceitação (90%-107%). Das 19 amostras analisadas, 14 apresentaram teor de PPD entre 1,74% a 3,65% p/p, em desacordo com a Legislação. Conclusões: O método proposto poderá contribuir com o monitoramento da qualidade e segurança de uso destes produtos

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor