miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449−/− mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449−/− mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449−/− mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449−/− cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis

Evaluation of different bowel preparations for small bowel capsule endoscopy: a prospective, randomized, controlled study

To obtain an adequate view of the whole small intestine during capsule endoscopy (CE) a clear liquid diet and overnight fasting is recommended. However, intestinal content can hamper vision in spite of these measures. Our aim was to evaluate tolerance and degree of intestinal cleanliness during CE following three types of bowel preparation. PATIENTS AND METHODS: This was a prospective, multicenter, randomized, controlled study. Two-hundred ninety-one patients underwent one of the following preparations: 4 L of clear liquids (CL) (group A; 92 patients); 90 mL of aqueous sodium phosphate (group B; 89 patients); or 4 L of a polyethylene glycol electrolyte solution (group C; 92 patients). The degree of cleanliness of the small bowel was classified by blinded examiners according to four categories (excellent, good, fair or poor). The degree of patient satisfaction, gastric and small bowel transit times, and diagnostic yield were measured. RESULTS: The degree of cleanliness did not differ significantly between the groups (P = 0.496). Interobserver concordance was fair (k = 0.38). No significant differences were detected between the diagnostic yields of the CE (P = 0.601). Gastric transit time was 35.7 +/- 3.7 min (group A), 46.1 +/- 8.6 min (group B) and 34.6 +/- 5.0 min (group C) (P = 0.417). Small-intestinal transit time was 276.9 +/- 10.7 min (group A), 249.7 +/- 13.1 min (group B) and 245.6 +/- 11.6 min (group C) (P = 0.120). CL was the best tolerated preparation. Compliance with the bowel preparation regimen was lowest in group C (P = 0.008). CONCLUSIONS: A clear liquid diet and overnight fasting is sufficient to achieve an adequate level of cleanliness and is better tolerated by patients than other forms of preparation

De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry

Hydrocephalus is one of the most prevalent form of developmental central nervous system (CNS) malformations. Cerebrospinal fluid (CSF) flow depends on both heartbeat and body movement. Furthermore, it has been shown that CSF flow within and across brain ventricles depends on cilia motility of the ependymal cells lining the brain ventricles, which play a crucial role to maintain patency of the narrow sites of CSF passage during brain formation in mice. Using whole-exome and whole-genome sequencing, we identified an autosomal-dominant cause of a distinct motile ciliopathy related to defective ciliogenesis of the ependymal cilia in six individuals. Heterozygous de novo mutations in FOXJ1, which encodes a well-known member of the forkhead transcription factors important for ciliogenesis of motile cilia, cause a motile ciliopathy that is characterized by hydrocephalus internus, chronic destructive airway disease, and randomization of left/right body asymmetry. Mutant respiratory epithelial cells are unable to generate a fluid flow and exhibit a reduced number of cilia per cell, as documented by high-speed video microscopy (HVMA), transmission electron microscopy (TEM), and immunofluorescence analysis (IF). TEM and IF demonstrate mislocalized basal bodies. In line with this finding, the focal adhesion protein PTK2 displays aberrant localization in the cytoplasm of the mutant respiratory epithelial cells

A questão da mulher e a Aids: novos olhares e novas tecnologias de prevenção The issue of the woman and Aids: new views and new technologies of prevention

A aids cresce em cifras no Brasil e no mundo. No mundo todo, cerca de 42 milhões de pessoas são soropositivas. Desde o início da década de 80 até setembro de 2003, foram notificados 277.154 casos de aids no Brasil. Atrás desses índices está uma triste realidade: a epidemia cresce 9 vezes mais entre as mulheres. São, no geral, jovens ou mulheres casadas ou que têm relacionamento fixo, sem comportamento promíscuo e que contraíram o vírus dentro de "casa". Junto à descoberta da contaminação pelo vírus, vem a dolorosa verdade da traição do parceiro, a implacável confirmação da fragilidade da relação conjugal vivida, mas principalmente, a morte do mito do amor ideal, guardado numa aliança ou numa união estável. Cada vez mais, vidas femininas são ceifadas assim, com essa história de amor incondicional relativo ao parceiro e total ausência de amor próprio. Devoção de um lado e negligência de outro. Mais do que uma suposta questão filosófica, antropológica ou ontológica, creio que, diante dos números apresentados, o baixo auto-cuidado feminino trata-se de um problema de saúde pública. Mas o que temos feito em termos de prevenção a Aids diante do segmento feminino e suas demandas? Na oportunidade deste relato, teceremos considerações sobre como nós, profissionais de saúde, podemos contribuir na gestão e desenvolvimento de novos programas e tecnologias de prevenção que alcancem o universo feminino e efetivamente desviem-no do comportamento de risco.<br>HIV grows in numbers in Brazil and around the world. In the whole world, about 42 millions people are HIV positive. Since the beginning of the 80's until September of 2003, there were 277.154 cases of HIV confirmed in Brazil. Behind those rates there is a sad reality: the epidemy grows at a rate 9 times higher among women. They are, in general, youngsters or married women or women with stable relationships, without promiscuous behavior and that acquired the virus inside their "home". Along with the discovery of the contamination caused by the virus, comes the painful truth of the betrayal of the partner, the implacable confirmation of the fragility of the conjugal relationship experienced, but mainly, the death of the ideal love myth, kept in an alliance or in a stable union. Each time more, feminine lives are reaped like this, with this story of unconditional love relative to the partner and total absence of self-esteem. Devotion, on one side and negligence, on another. More than a supposed philosophical, anthropological or ontological issue, I believe that in face of the numbers presented, the low feminine self-care is linked to a of public health problem. In this article, we will weave considerations about how we, health professionals can contribute to the management and development of new programs and prevention technologies that reach the feminine universe and effectively deviate it from the risk behavior

New dye-labeled terminators for improved DNA sequencing patterns.

We have used two new dye sets for automated dye-labeled terminator DNA sequencing. One set consists of four, 4,7-dichlororhodamine dyes (d-rhodamines). The second set consists of energy-transfer dyes that use the 5-carboxy-d-rhodamine dyes as acceptor dyes and the 5- or 6-carboxy isomers of 4'-aminomethylfluorescein as the donor dye. Both dye sets utilize a new linker between the dye and the nucleotide, and both provide more even peak heights in terminator sequencing than the dye-terminators consisting of unsubstituted rhodamine dyes. The unsubstituted rhodamine terminators produced electropherograms in which weak G peaks are observed after A peaks and occasionally C peaks. The number of weak G peaks has been reduced or eliminated with the new dye terminators. The general improvement in peak evenness improves accuracy for the automated base-calling software. The improved signal-to-noise ratio of the energy-transfer dye-labeled terminators combined with more even peak heights results in successful sequencing of high molecular weight DNA templates such as bacterial artificial chromosome DNA

ESTUDIO MORFOLÓGICO DE LA TUBERCULOSIS CAPRINA. L. TUBERCULOSIS PULMONAR

Tuberculous lesions were found in the lung of 35 goats from the Region of Murcia (Spain). The animals were selected because of a positive reaction to de CTID test. Bacteriological analysis allowed the isolation of Mycobacterium bovis (10 animals) and M. tuberculosis (1 animal). In addition to lung lesions were found in other organs and different types of lymph nodes, depending on the degree of generalization of the disease. A primary complex was found in 5 animals (14.28%); early generalization was found in 12 animals (34.29%); organic-chronic tuberculosis was found in 14 animals (40%); and late generalization in 5 animals (14.28%). These data reveal that caprine tuberculosis has a high incidence in the Region of Murcia. thus indicating a potential risk of transmission of the disease to man.Las lesiones tuberculosas fueron encontradas en los pulmones de 35 cabras procedentes de distintos rebaños de la Región de Murcia (España). Los animales fueron seleccionados por dar positiva la prueba de la intradermorreacción tuberculínica comparativa. El análisis bacteriológico reveló la presencia de Mycobacterium bovis en 10 animales y Mycobacterium tuberculosis en un animal. Además de las lesiones pulmonares se encontraron lesiones en otros órganos y en diferentes gánglios linfáticos, dependiendo del grado de generalización de la enfermedad. La fase de complejo primario se encontró en 5 animales (14.28%); de generalización precoz en 12 animales (34.29%); de tuberculosis orgánica crónica en 14 animales (40%); de generalización tardía en 5 animales (14.28%). La tuberculosis caprina tiene una alta incidencia y distribución en la Región de Murcia y es un importante factor de riesgo en la transmisión de la enfermedad al hombre

ESTUDIO MORFOLÓGICO DE LA TUBERCULOSIS CAPRINA. II. TUBERCULOSIS GENERALIZADA

Generalization of tuberculosis was found in 24 of 35 goats in which pulmonary tuberculosis was diagnosed. Lesions of early generalization were found in spleen (7 animals), liver (12 animals), intestine (7 animals), heart (1 animal) and kidney (1 animal), where as lesions of late generalization were found only in one case in kidney. The lymph nodes of the affected organs and frequently the superficial lymph nodes (17 animals) showed lesions. Microscopically all animals presenled the tubercular granulomas which characterised this disease.La forma generalizada de la tuberculosis se encontró en 24 de las 35 cabras diagnosticadas de tuberculosis pulmonar. Las lesiones de generalización precoz se observaron en bazo (7 animales), hígado (12 animales). intestino (7 animales), corazón (1 animal) y riñón (1 animal), mientras que la fase de generalización tardía sólo se demostró en un caso en riñón. Los ganglios linfáticos de los órganos afectados siempre presentaron las mismas lesiones. Los ganglios linfáticos superficiales estaban afectados en 17 animales. Microscópicamente todos los animales demostraron granulomas tuberculosos característicos de la enfermedad