BackgroundConventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy.MethodsWe developed an advanced noninvasive prenatal diagnosis method based on massively parallel sequencing. The Noninvasive Fetal Trisomy (NIFTY) test, combines an optimized Student’s t-test with a locally weighted polynomial regression and binary hypotheses. We applied the NIFTY test to 903 pregnancies and compared the diagnostic results with those of full karyotyping.Results16 of 16 trisomy 21, 12 of 12 trisomy 18, two of two trisomy 13, three of four 45, X, one of one XYY and two of two XXY abnormalities were correctly identified. But one false positive case of trisomy 18 and one false negative case of 45, X were observed. The test performed with 100% sensitivity and 99.9% specificity for autosomal aneuploidies and 85.7% sensitivity and 99.9% specificity for sex chromosomal aneuploidies. Compared with three previously reported z-score approaches with/without GC-bias removal and with internal control, the NIFTY test was more accurate and robust for the detection of both autosomal and sex chromosomal aneuploidies in fetuses.ConclusionOur study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis.

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Nuclear factor-kappa B (NFκB) is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB). However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase) or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy.

The otologic surgeon must continue to familiarize himself with the anatomy of the temporal bone. For this purpose, we made precise histologic measurements of the cochlear aqueduct, round window membrane, round window niche, and facial recess. Measurements were taken from a large series of sectioned temporal bones and analyzed according to age. Our results demonstrated a high degree of individual variability in each area measured.

The transsphenoidal approach in a vidian neurectomy is a simple method that removes the need for sphenopalatine artery ligation and causes less surgical morbidity. However, the possibility of recurrence of this condition in the long term needs further investigation.

The bacterial findings of 73 maxillary sinuses in 48 patients with chronic maxillary sinusitis, together with 7 non-inflamed sinuses, are reported. Employing an intraoperative technique and simultaneous collection of 3 different types of specimens in the present investigation made possible comparison of their bacterial characteristics. The results indicated that intraoperative culture of antral mucosa seems to provide the most reliable finding of bacterial flora in chronic maxillary sinusitis. The anaerobic bacteria were never found in the mucosal culture of non-inflamed sinus. The anaerobes appeared to invade the sinus cavity following the sealing of the ostium through the lymphatic or venous system and maintain the inflammatory process. Microbiological analysis of the results between the infected and non-inflamed sinuses established anaerobic bacteria as the most important pathogen in chronic maxillary sinusitis. The predominant anaerobes recovered in descending order of frequency were Veillonella sp., Peptococcus sp., Propionibacterium acne and anaerobic nonspore-forming GPB. Statistical analysis of the results of mucosal culture of inflamed and control materials demonstrated that those aerobic and faculatative bacteria recovered in the inflamed sinus appeared to be the normal inhabitants of non-inflamed sinus mucosa. The presence of normal flora in the normal healthy sinus mucosa may explain the chain of events that follows the occlusion of the ostium. These aerobic bacteria may become pathogenic and play a role in the pathogenesis of sinusitis.

IgA-producing plasma cells appear to be derived from GALT germinal centers in humans. B-cell receptor engagement promotes formation of germinal centers of GALT, with no more evidence for innate immune receptor activation in the mucosa than nonintestinal immune compartments. Germinal centers in GALT should be targets of mucosal vaccinations because they are the source of human intestinal IgA response.

Our experience in a few selected patients shows that the functional outcome of tongue surgery is related to the reconstruction methods used (for speech) and to the extent of tongue resection (for swallowing).