A mild form of SLC29A3 disorder: a frameshift deletion leads to the paradoxical translation of an otherwise noncoding mRNA splice variant

We investigated two siblings with granulomatous histiocytosis prominent in the nasal area, mimicking rhinoscleroma and Rosai-Dorfman syndrome. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous frameshift deletion in SLC29A3, which encodes human equilibrative nucleoside transporter-3 (hENT3). Germline mutations in SLC29A3 have been reported in rare patients with a wide range of overlapping clinical features and inherited disorders including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, and Faisalabad histiocytosis. With the exception of insulin-dependent diabetes and mild finger and toe contractures in one sibling, the two patients with nasal granulomatous histiocytosis studied here displayed none of the many SLC29A3-associated phenotypes. This mild clinical phenotype probably results from a remarkable genetic mechanism. The SLC29A3 frameshift deletion prevents the expression of the normally coding transcripts. It instead leads to the translation, expression, and function of an otherwise noncoding, out-of-frame mRNA splice variant lacking exon 3 that is eliminated by nonsense-mediated mRNA decay (NMD) in healthy individuals. The mutated isoform differs from the wild-type hENT3 by the modification of 20 residues in exon 2 and the removal of another 28 amino acids in exon 3, which include the second transmembrane domain. As a result, this new isoform displays some functional activity. This mechanism probably accounts for the narrow and mild clinical phenotype of the patients. This study highlights the"rescue" role played by a normally noncoding mRNA splice variant of SLC29A3, uncovering a new mechanism by which frameshift mutations can be hypomorphic.

Aspectos fonéticos del proceso de velarización en las nasales del español y del catalán

La producción de las nasales exige simultáneamente una oclusión dentro de la boca y una salida de aire por el canal rinofaríngeo y esta característica las distingue de las demás articulaciones de los inventarios de las lenguas. La salida de aire por la nariz es el requisito articulatorio más definitorio y permite que la oclusión bucal no precise unos requisitos tan estrictos con lo cual se puede adaptar fácilmente a la articulación siguiente cuando la nasal aparece en posición implosiva. Ante oclusiva velar es sabido que la nasal sufre un proceso de velarización y atrasa su punto de articulación hacia la parte posterior de la cavidad bucal. el presente trabajo pretende profundizar en este tipo de coarticulación en grupos consonánticos nasal + oclusiva velar para evaluar aspectos fonéticos, necesariamente alofónicos, en español y catalán. Concretamente se profundiza en el efecto de varios factores (la velocidad de habla, la ocurrencia de la nasal en sílaba tónica o átona, la presencia de una frontera morfológica o no en el grupo consonántico y la sordez-tensión o sonoridad-laxitud de la oclusiva siguiente) a partir de los datos obtenidos de tres informantes en cada lengua en diversos ítems repetidos cada uno de ellos cuatro veces y analizados mediante el electropalatógrafo WinePG. Los resultados señalan la importancia de los factores estudiados, especialmente de la tensión o la sonoridad de la oclusiva siguiente. Asimismo se constata la tendencia en habla rápida a la hipoarticulación a diferencia de lo que sucede en habla lenta, velocidad que favorece la hiperarticulación y la pérdida de la asimilación en algunas muestras de dos de los informantes. este hecho unido a la existencia de emisiones que podrían presentar un cierto tipo de asimilaciones parciales nos hace pensar que el proceso de asimilación debe ser visto más bien de forma gradual que categórica.

Construcció d'un equip per a la producció de cervesa artesana

Catalunya és un dels territoris on hi ha hagut més auge del sector de la cervesa artesana, i són molt nombroses les microcerveseries i les botigues especialitzades on es poden trobar els recursos materials necessaris, a més de ser centres difusió de coneixements relacionats. Així, doncs, aquest projecte està emmarcat en un context que permet el desenvolupament de tècniques d’elaboració de cervesa artesana. Aquest projecte es basa en la construcció d’un equip amb materials reutilitzats i amb un pressupost limitat que permet reproduir a petita escala els processos d’elaboració que es duen a terme en les microcerveseries artesanes actuals. El projecte s’ha assentat sobre la comprensió dels fonaments teòrics i pràctics del procés d’elaboració de cervesa, i amb l’experiència inicial d’elaboració de cervesa amb un equip bàsic de tipus homebrewer. Per minimintzar costos els tancs s’han construït a partir de barrils de cervesa i les parts sobrants s’han aprofitat per a altres elements. S’han emprat elements quotidians com una olla a pressió i s’ha construït un sistema regulador de pressió (per al tanc de fermentació cilindrocònic isobàric construït) en lloc d’adquirir-lo. S’ha posat l’èmfasi en minimitzar la necessitat de manipulació manual durant l’elaboració. Per tant, s’han instal·lat els components de l’equip formant un circuit tancat amb sistema de bombeig, i s’ha incorporat un sistema que permet el control i la lectura de les temperatures de cada procés. Altres elements són el sistema de filtres amb mecanisme de tub en forma d’ela (que permet l’extracció del most dels tanc de maceració i de cocció d’una manera efectiva i sense necessitat de manipulació) i el sistema de dutxa (que permet automatitzar el procés de rentat i filtrat). Un element que distingeix aquest equip d’altres equips emprats en algunes microcerveseries artesanes és el tanc de fermentació cilindrocònic isobàric amb vàlvula controladora de pressió, que permet prescindir de la doble fermentació en ampolla, ja que permet aprofitar el gas carbònic produït durant la fermentació per la carbonatació de la cervesa. Es pot concloure que gràcies a les seves característiques, l’equip permet realitzar successives elaboracions obtenint el mateix producte amb les mateixes característiques organolèptiques, principalement gràcies a la cambra de fermentació, que permet realitzar les etapes de fermentació, maduració i clarificació controlant la temperatura desitjada; al tanc de maceració amb aïllament, que permet realitzar el procés a temperatura constant sense pèrdues tèrmiques i al sistema de control de temperatura de totes les etapes. L’únic inconvenient és que, degut a la manca pressupostària, ha estat impossible l’adquisició d’un sistema d’embotellament isobàric que permeti realitzar l’embotellament sense pèrdues del gas carbònic. Per tant, el producte final pot embotellar-se amb una lleugera pèrdua de gas o es pot emmagatzemar en el mateix fermentador cilindrocònic per al seu consum directe, a l’estil d’alguns brewpubs.

Cavernous sinus syndrome due to rhino-orbital-cerebral mucormycosis

The present report describes the case of a 43-year-old diabetic patient with facial pain, protruding eyes, nasal congestion and decreased right vision (involvement of the ipsilateral cranial nerves III, IV and V). Computed tomography showed diffuse sinusitis at right, cribriform plate erosion and presence of a hypodense collection in the frontal lobe with peripheral enhancement. Magnetic resonance imaging confirmed the presence of a cerebral abscess. Samples were collected from the lesion, confirming hyphae compatible with mucormycosis.

Radiographic adenoid evaluation: proposal of an objective parameter

Objective The objective of the present study was to evaluate current radiographic parameters designed to investigate adenoid hypertrophy and nasopharyngeal obstruction, and to present an alternative radiographic assessment method. Materials and Methods In order to do so, children (4 to14 years old) who presented with nasal obstruction or oral breathing complaints were submitted to cavum radiographic examination. One hundred and twenty records were evaluated according to quantitative radiographic parameters, and data were correlated with a gold-standard videonasopharyngoscopic study, in relation to the percentage of choanal obstruction. Subsequently, a regression analysis was performed in order to create an original model so the percentage of the choanal obstruction could be predicted. Results The quantitative parameters demonstrated moderate, if not weak correlation with the real percentage of choanal obstruction. The regression model (110.119*A/N) demonstrated a satisfactory ability to “predict” the actual percentage of choanal obstruction. Conclusion Since current adenoid quantitative radiographic parameters present limitations, the model presented by the present study might be considered as an alternative assessment method in cases where videonasopharyngoscopic evaluation is unavailable.

Severe Cutaneous Leishmaniasis in a Human Immunodeficiency Virus Patient Coinfected with Leishmania braziliensis and Its Endosymbiotic Virus.

Leishmaniaparasites cause a broad range of disease, with cutaneous afflictions being, by far, the most prevalent. Variations in disease severity and symptomatic spectrum are mostly associated to parasite species. One risk factor for the severity and emergence of leishmaniasis is immunosuppression, usually arising by coinfection of the patient with human immunodeficiency virus (HIV). Interestingly, several species ofLeishmaniahave been shown to bear an endogenous cytoplasmic dsRNA virus (LRV) of theTotiviridaefamily, and recently we correlated the presence of LRV1 withinLeishmaniaparasites to an exacerbation murine leishmaniasis and with an elevated frequency of drug treatment failures in humans. This raises the possibility of further exacerbation of leishmaniasis in the presence of both viruses, and here we report a case of cutaneous leishmaniasis caused byLeishmania braziliensisbearing LRV1 with aggressive pathogenesis in an HIV patient. LRV1 was isolated and partially sequenced from skin and nasal lesions. Genetic identity of both sequences reinforced the assumption that nasal parasites originate from primary skin lesions. Surprisingly, combined antiretroviral therapy did not impact the devolution ofLeishmaniainfection. TheLeishmaniainfection was successfully treated through administration of liposomal amphotericin B.

Leishmaniavirus : a possible target against metastatic leishmaniasis

Leishmaniasis is widely spread disease found in bath tropical and temperate regions but limited to the habitat of its sand fly vector. lt affects over 12 million people with 2 million new cases each year. As cutaneous leishmaniasis patients show varying levels of immunity to the disease after recovery, the development of a vaccine has much promise as a prevention strategy. Unfortunately however, existing anti-leishmanial vaccines are plagued by safety issues and have only ever shown limited efficacy .So, despite much effort, no effective vaccine is currently available. Recent studies suggest a correlation between the presence of Leishmania RNA virus (LRV) and the development of mucocutaneous leishmaniasis (MCL), which is characterised by the presence of secondary lesions in nasal and buccal mucosa, causing destructive and disfiguring facial lesions. Moreover, recent research has associated the viral presence to treatment fa ilure in patients. ln the first part of this work, we propose that these viral particles may serve as promising vaccine candidates due to their powerful TLR-3 antigenicity, launching an early cell-mediated attack on stimulated cells and thus eliminating their virulent complications. The second part of this work discusses a preliminary study on the lymphocyte immune response against Leishmania guyanensis infection. The lymphocyte response (and in particular, the raie of CDS+ T cells) is controversial and varies greatly between Leishmania species. Here, we illustrate the importance of a small CDS+ T cell subpopulation, expressing the CDSaa+ receptor. These intraepithelial lymphocytes are mainly present in the skin, vagina and intestinal tissue and are best known for their raie in the early immune response against pathogens. Similarly to traditional CDS+ cells, they secrete the tissue-destructive enzymes, perforin and granzyme, which can result in a hyper-inflammatory cutaneous lesion, raising a possibility for their raie in Leishmania infection. lndeed, our initial results in a murine mode( of Leishmania guyanensis infection suggest a pathogenic raie for CDSaa+ T cells. Further research into species-specific immune responses against the various Leishmania parasites is critical to realising the clinical potential of immunotherapy in the treatment and prevention of this disfiguring disease . -- La Leishmaniose est une maladie infectieuse causée par le parasite Leishmania. Elle est localisée dans les régions où son vecteur se reproduit, c'est-à-dire dans des régions tropicales ou tempérées. Cette pathologie affecte 12 millions des personnes dans le monde et 2 millions de nouveaux cas sont recensés chaque année. D'autres facteurs, tels la déforestation, les conditions d'hygiène ou encore l'accès limité aux médicaments, aggravent la pathologie et renforcent sa propagation. Les patients affectés par la leishmaniose et qui arrivent à en guérir, présentent une protection contre une réinfection. Pour cette raison, le développement d'un vaccin reste la meilleure solution pour combattre ce fléau. Mais, à ce jour, et malgré beaucoup d'efforts, aucun vaccin efficace n'a encore été développé. Un autre facteur responsable de l'aggravation de la pathologie et de la résistance de ces parasites aux drogues est un virus qui peut infecter certaines souches de Leishmania. Ce virus, appelé Leishmania RNA virus, peut induire une réponse inflammatoire exagérée, ce qui a comme résultat l'aggravation de la pathologie, la survie et la dissémination de ce parasite au sein de l'hôte infecté. Vu l'absence d'un vaccin contre ce parasite, Leishmania, nous proposons de développer un vaccin non pas contre le parasite lui- même mais contre l'agent qui provoque l'exacerbation de la pathologie, c'est-à-dire le virus. Dans cette étude, nous décrivons le développement d'un vaccin contre LRV, qui empêche le parasite d'induire des inflammations exagérées dans les souris. En d'autres mots, nous essayons de prévenir toutes les complications générées par cet hyperpathogène qu'est le LRV, en utilisant sa capside comme cible pour le développement d'un vaccin. Dans la deuxième partie de ce manuscrit, nous avons aussi étudié plus en détail la réponse immunitaire, et en particulier la réponse des lymphocytes T COB suite à l'infection du parasite Leishmania guyanensis porteur du LRV.

Sleep-Disordered Breathing in Women

Sleep-disordered breathing (SDB) is underdiagnosed in women, probably due to the different gender-related manifestation. We investigated the differences in presentation, symptoms and co-morbidities of SDB in men and in pre- and postmenopausal women by a clinical, retrospective, cross-sectional study of 601 consecutively referred women and 233 age- and BMI-matched male-female pairs studied with the static-chargesensitive bed (SCSB) and an oximeter. Data on the use of nasal CPAP were gathered from the Paimio hospital database, and the co-morbidity information was based on reimbursed medication data from the National Agency for Medicines and the Social Insurance institution. The abnormal breathing episodes at night were more frequent in men than in women, and in postmenopausal women compared to premenopausal ones. Partial upper airway obstruction was the most common type of SDB in both genders but especially in females. BMI and the major symptoms of SDB were similar in pre- and postmenopausal women, and a menopause effect on symptoms was not found. CPAP adherence did not differ between symptomatic patients with partial upper airway obstruction and those presenting with conventional obstructive sleep apnea. Comorbidities were more frequent in SDB patients than in the general Finnish population. Compared to sleep apnea, partial upper airway obstruction was associated with a threefold prevalence of asthma and/or COPD in both genders, and with a 60% reduced prevalence of hypertension in females matched for age and BMI. Our results emphasize that partial upper airway obstruction is not a milder form of SDB but a different entity, the severity of which is underestimated when using the conventional apnea-hypopnea index. It seems clinically relevant to diagnose and treat the co-morbidities and SDB also in patients with partial upper airway obstruction, especially in elderly and symptomatic women.

A topical microemulsion for the prevention of allergic rhinitis symptoms: results of a randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial (Nares study)

Background: Since barrier protection measures to avoid contact with allergens are being increasingly developed, we assessed the clinical efficacy and tolerability of a topical nasal microemulsion made of glycerol esters in patients with allergic rhinitis. Methods: Randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial in which adult patients with allergic rhinitis or rhinoconjunctivitis due to sensitization to birch, grass or olive tree pollens received treatment with topical microemulsion or placebo during the pollen seasons. Efficacy variables included scores in the mini-RQLQ questionnaire, number and severity of nasal, ocular and lung signs and symptoms, need for symptomatic medications and patients" satisfaction with treatment. Adverse events were also recorded. Results: Demographic characteristics were homogeneous between groups and mini-RQLQ scores did not differ significantly at baseline (visit 1). From symptoms recorded in the diary cards, the ME group showed statistically significant better scores for nasal congestion (0.72 vs. 1.01; p = 0.017) and mean total nasal symptoms (0.7 vs. 0.9; p = 0.045). At visit 2 (pollen season), lower values were observed in the mini-RQLQ in the ME group, although there were no statistically significant differences between groups in both full analysis set (FAS) and patients completing treatment (PPS) populations. The results obtained in the nasal symptoms domain of the mini-RQLQ at visit 2 showed the highest difference (−0.43; 95% CI: -0.88 to 0.02) for the ME group in the FAS population. The topical microemulsion was safe and well tolerated and no major discomforts were observed. Satisfaction rating with the treatment was similar between the groups. Conclusions: The topical application of the microemulsion is a feasible and safe therapy in the prevention of allergic symptoms, particularly nasal congestion.

Anatomia macroscòpica i microscòpica de l'aparell genital femení d'Ophidion barbatum (L.) (Pisces, Ophididae)

S'ha realitzat un estudi de l'anatomia macroscòpica i microscòpica de I'ovari d'Ophidion barbatum (L.) (Pisces, Ophidiidae), utilitzant material recollit per pescadors del port de Blanes (mar català) durant el mes d'octubre de 1985. L'absència d'òrgan copulador en els mascles d'aquesta espècie i la posició de l'orifici nasal anterior, a una certa alçada respecte al llavi superior, ens permet identificar-la com una espècie ovípara, del subordre Ophidioidei, dins de l'ordre Ophidiiformes. L'ovari és únic i continuat caudalment per l'oviducte. Els nombrosos cordons intraovarics que tapien la cavitat augmenten considerablement la superfície germinal. El desenvolupament de l'ovari es correspon amb el tipus asincrònic (Marza, 1938) i la fresa repetida al llarg d'una estació reproductiva més o menys llarga és una estrategia que augmenta la fecunditat, normalment limitada pel volum corporal de la femella. Dins de l'ordre Ophidiiformes, el tipus d'ovari únic sense restes de paret mitjana sembla ser la norma entre les espècies de reproducció ovípara. Aquest fet esta en contradicció amb la teoria de Mendoza (1943) que, fora d'algunes excepcions, l'ovari únic es troba principalment en els teleostis vivípars

Notas sobre los énfasis de palabra en los titulares televisivos

Este artículo aporta unos primeros resultados acerca de los énfasis de palabra en titulares televisivos en catalán. De entrada, se subraya la poca sujeción de la palabra sobre la imagen y se sitúan los patrones melódicos más habituales en este contexto informativo. El núcleo del texto se centra en la descripción de los énfasis de palabra ascendente que tienen lugar en los numerales y en palabras con una sílaba acabada en lateral o nasal, y, colateralmente, aborda los énfasis de regularidad y de irregularidad, ya que se caracterizan por ser un conjunto de énfasis de palabra ascendente que se dan de forma regular o irregular en el cuerpo del enunciado.

Set-up of a method using LC-UV to assay mometasone furoate in pharmaceutical dosage forms

A reliable method using LC-UV to assay mometasone furoate (MF) in creams or nasal sprays using the same chromatographic conditions was set up. Methanol:water 80:20 (v/v) (1.0 mL min-1) was used as mobile phase. MF was detected at 248 nm and analyzed in a concentration range from 1.0 to 20.0 µg mL-1. The method provided acceptable theoretical plates, peak simmetry, peak tailing factor and peak resolution a short run (5 min). The method showed specificity, good linearity (r = 0.9999) and the quantification limit was 0.379 µg mL-1. Furthermore, the method was precise (RSD < 2.0%), accurate (recovery > 97%) and robust.

Projeto terapêutico singular no âmbito da saúde mental: uma experiência no curso de graduação em medicina

O Jardim Campo Belo, localizado no município de Campinas (SP), é um bairro de alta vulnerabilidade social e grande demanda por serviços de saúde, sendo a única oferta em saúde mental o matriciamento com outra unidade de saúde. Neste contexto, durante as disciplinas do segundo ano de Medicina, foi realizado um projeto de intervenção no Centro de Saúde, mediante acompanhamento em domicilio de pacientes usuários de psicotrópicos. Realizaram-se visitas quinzenais às casas de dez pacientes. Nestas visitas, trabalhou-se um roteiro semidirigido, em que se buscou conhecer as demandas de cada paciente. Alguns destes aumentaram os cuidados com a própria saúde, e num caso houve até suspensão do uso dos medicamentos psicotrópicos, em parceria com a equipe; em outros casos, as visitas serviram como válvula de escape social, tornando-se um espaço onde se ofertava atenção aos que estavam acostumados ao abandono social. Os alunos envolvidos relatam grande aprendizado graças às vivências e ao envolvimento com o tema, que se tornou um grande suplemento pedagógico.

Desenvolvimento e avaliação de uma servoválvula de baixo custo para a aplicação de insumos líquidos

O presente trabalho teve o objetivo de desenvolver uma servoválvula de baixo custo, que respondesse a um sinal eletrônico de controle, para a aplicação de insumos líquidos a taxas variáveis. Depois de realizada pesquisa na literatura das opções de válvulas existentes para a dosagem de líquidos a baixas pressões, partiu-se para o desenvolvimento de uma válvula proporcional com acionamento mecânico por intermédio de um servomotor controlado eletronicamente. Uma vez desenvolvida a servoválvula, o sistema foi submetido a um conjunto de testes, realizados em bancada desenvolvida especificamente para esse fim, onde se procurou avaliar seu comportamento em termos de repetitividade, histerese e linearidade. Como resultados, obtiveram-se três curvas de vazão em função do percentual de abertura, descrevendo três incrementos de abertura e fechamento em duas pressões diferentes de trabalho. A servoválvula apresentou boa repetitividade, razoável histerese e curva tipicamente quadrática, bem como manteve a proposta de baixo custo. Esses resultados apresentaram-se bastante satisfatórios, uma vez que a não-linearidade e a histerese podem ser facilmente corrigidas por meio de software.

Desempenho de válvulas antigotas e microaspersores

Nos últimos anos, foram introduzidos novos modelos de dispositivos para cultivo em ambiente protegido, como as válvulas antigotas e microaspersores, necessitando-se avaliar o desempenho dos mesmos. Assim, o objetivo deste trabalho foi avaliar o desempenho hidráulico de válvulas antigotas novas e usadas, sob baixa e alta pressão, em microaspersores do grupo modular e modelo Hadar. O CVf e CVq do conjunto microaspersor e válvula antigotas de baixa pressão e somente o microaspersor modular foram classificados como ruins ou inaceitáveis e a válvula anti-gotas modular de alta pressão nova como inaceitável. A válvula Hadar apresentou o melhor desempenho para todas as pressões de serviço. As válvulas avaliadas abriram em pressões inferiores às indicadas pelos seus fabricantes. O tempo de uso interferiu no desempenho das válvulas antigotas modular de baixa pressão, sendo o modelo novo o que apresentou menor índice de CVf para a pressão de abertura e fechamento.