Identification of pyridine analogs as new predator-derived kairomones.

In the wild, animals have developed survival strategies relying on their senses. The individual ability to identify threatening situations is crucial and leads to increase in the overall fitness of the species. Rodents, for example have developed in their nasal cavities specialized olfactory neurons implicated in the detection of volatile cues encoding for impending danger such as predator scents or alarm pheromones. In particular, the neurons of the Grueneberg ganglion (GG), an olfactory subsystem, are implicated in the detection of danger cues sharing a similar chemical signature, a heterocyclic sulfur- or nitrogen-containing motif. Here we used a "from the wild to the lab" approach to identify new molecules that are involuntarily emitted by predators and that initiate fear-related responses in the recipient animal, the putative prey. We collected urines from carnivores as sources of predator scents and first verified their impact on the blood pressure of the mice. With this approach, the urine of the mountain lion emerged as the most potent source of chemical stress. We then identified in this biological fluid, new volatile cues with characteristic GG-related fingerprints, in particular the methylated pyridine structures, 2,4-lutidine and its analogs. We finally verified their encoded danger quality and demonstrated their ability to mimic the effects of the predator urine on GG neurons, on mice blood pressure and in behavioral experiments. In summary, we were able to identify here, with the use of an integrative approach, new relevant molecules, the pyridine analogs, implicated in interspecies danger communication.

Avaliação radiográfica da adenóide em crianças: métodos de mensuração e parâmetros da normalidade

A radiografia da nasofaringe (ou radiografia do cavum) ainda é o exame por imagem mais usado para a avaliação do tamanho da adenóide. Dada a variedade e a complexidade dos métodos de mensuração preconizados, muitos radiologistas preferem a avaliação subjetiva, que pode ser imprecisa e não-acurada. Esta revisão enumera e descreve os diversos métodos de mensuração radiográfica da adenóide propostos na literatura, considerando praticidade, acurácia e precisão, com o objetivo de indicar os mais adequados para a prática cotidiana.

Galanin pathogenic mutations in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the TLE in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatment.

Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia.

We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of "mitochondrial chaperonopathies" and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis.

Diagnóstico por imagem dos tumores da nasofaringe

A nasofaringe é a parte mais superior das vias aéreas superiores. Seu limite superior é a base do osso esfenóide e occipital, situa-se anteriormente às duas primeiras vértebras cervicais e à frente do clivo. Seus limites laterais são formados pelas margens do músculo constritor superior da faringe e pela fáscia faringobasilar, recessos faríngeos, toro tubário e tuba auditiva. O limite inferior é um plano horizontal que passa pelo palato duro e pelo músculo palatofaríngeo. Anteriormente, comunica-se com a cavidade nasal via coana posterior. Mede cerca de 2,0 cm de diâmetro ântero-posterior e cerca de 4,0 cm de extensão crânio-caudal. O carcinoma de células escamosas compreende aproximadamente 70% a 98% de todas as neoplasias malignas da nasofaringe em adultos. Este tipo de tumor apresenta alta incidência na população asiática, sendo mais comum entre os homens e o terceiro mais comum entre as mulheres. A manifestação clínica do carcinoma da nasofaringe depende do tamanho da lesão e da sua localização, sendo que as lesões de pequenas dimensões são geralmente assintomáticas. A tomografia computadorizada e a ressonância magnética desempenham papel essencial e complementar no estadiamento e no tratamento dos pacientes portadores de câncer da nasofaringe.

Variações anatômicas do complexo ostiomeatal: achados tomográficos em 200 pacientes

OBJETIVO: O objetivo deste trabalho foi verificar a freqüência e os tipos de variações anatômicas do complexo ostiomeatal. MATERIAIS E MÉTODOS: Foram revisadas 200 tomografias computadorizadas de pacientes com suspeita clínica de sinusopatia. RESULTADOS: Observamos um ou mais tipos de variações anatômicas em 83,5% dos pacientes, as mais freqüentes envolvendo o corneto médio (84%) e o septo nasal (34%). Outras variantes anatômicas comuns encontradas foram a presença de aeração do agger nasi e células etmoidais infra-orbitárias (células de Haller). CONCLUSÃO: As variações anatômicas do complexo ostiomeatal anterior são muito corriqueiras. As mais freqüentes envolvem o corneto médio e o septo nasal.

Schwannoma of the inferior turbinate: case report and review of literature

Schwannomas of the sinonasal tract are rare entities that are amenable to local resection. We present a 69 year old woman with a schwannoma of the inferior turbinate that was successfully resected. Schwannomas arising from the inferior turbinate are very infrequent.

Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study.

BACKGROUND: Pregnant women with asthma need to take medication during pregnancy. OBJECTIVE: We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy. METHODS: We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries. RESULTS: Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled β2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled β2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting β2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85). CONCLUSIONS: The study confirmed increased odds of first-trimester exposure to inhaled β2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting β2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.

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.

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

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.