An epigenome-wide association study meta-analysis of educational attainment.

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Distribution of the crossed olivocochlear bundle in the chinchilla's cochlea.

The efferent crossed olivocochlear bundle (COCB) was transected in the brain stem of the chinchilla, and the animals sacrificed 7 to 96 days later. Electron microscopy revealed that all the large efferent nerve endings on outer hair cells in the basalmost 2 mm (round window region) of the cochlea had degenerated, 87.5% in the remainder of the first turn, 70% in the second turn and 43% in the third turn. Only a few degenerating nerve fibers were seen in the medial spiral tract (inner spiral and tunnel bundles) of the experimental animals. Nerve fibers were counted in the medial spiral tracts of the cochleas of control animals as well as in those animals whose COCB had been transected. There were considerable individual variations in the fiber numbers, and statistical analysis showed no significant difference between the numbers of nerve fibers in normal and experimental animals. The cochlear microphonics (CM) and nerve action potentials (AP) of acute animals were assessed before and after COCB section. The CM and AP of the chronic experimental animals were compared with responses from normals. Overall, no changes in a physiological response of the anesthetized chinchilla could be attributed to complete section of the COCB.

The junctions of the spindle-shaped cells of the stria vascularis: a link that completes the barrier between perilymph and endolymph.

It is current opinion that the intercellular spaces of the stria vascularis represent a closed compartment isolated from the endolymph by the tight junctions of the marginal cells and from the perilymph by the junctional complexes of the basel cells. However, it has not yet been investigated whether these two barriers meet at the stria margins toward Reissner's membrane and the spiral prominence. Possible candidates for this sealing could be junctions between the spindle-shaped cells. In the present study freeze-fracture replicas of guinea pig specimens fixed in the presence of filipin were used in order to investigate the junctions of the spindle-shaped cells and to localize the cholesterol in their plasma membrane. Replicas reveal that, below the belt-like apical zonula occludens, the basolateral plasma membranes of the spindle-shaped cells adjacent to each other and to the basal cells are joined over their entire extension by a large number of junctional strands intermingled with numerous filipin-cholesterol-complexes. Gap junctions are present in the meshes formed by these junctional strands. Thus, the plasma membrane of the spindle-shaped cells shows morphological and cytochemical characteristics which indicate that they are the anatomical components completing the barrier isolating the intrastrial compartment from the surrounding fluids.

Brain herniation into the middle ear: two idiopathic cases treated by a combined intracranial-mastoid approach.

One hundred thirty-nine cases of brain herniation into the middle ear and mastoid have been reported in the world literature during the last 40 years. In 29 cases the herniation was idiopathic. In idiopathic cases, intermittent CSF otorhinorrhea, a history of intermittent "serous otitis media," and a conductive hearing loss were the main clinical findings. Polytomography or CT-scan revealed a tegmen antri or tympani defect in some patients. There are three surgical approaches for treatment of brain herniation into the middle ear: neurosurgical, otological, and combined.

Hearing results of ossiculoplasty in Austin-Kartush group A patients.

OBJECTIVE: To compare hearing results in patients who underwent ossiculoplasty for Austin-Kartush group A impairments (incus erosion, malleus handle present, stapes superstructure present) with the results in patients with an intact ossicular chain who required only myringoplasty. The literature on hearing results of ossiculoplasty with different types of prostheses and different techniques is reviewed. PATIENTS AND STUDY DESIGN: This study retrospectively reviews a series of 181 consecutive ossiculoplasties and 204 consecutive myringoplasties. SETTING: The study was carried out partly at a private practice and partly in an academic tertiary referral center. MAIN OUTCOME MEASURES: This study complies with levels 1 and 2 of the guidelines recommended by the American Academy of Otolaryngology--Head and Neck Surgery (1995). RESULTS: When success was defined as a postoperative air-bone gap within 10 dB, the success rate was higher for myringoplasty (81%) than for ossiculoplasty (55%). When success was defined as a postoperative air-bone gap within 20 dB, the success rate was 97% in myringoplasties and 85% in ossiculoplasties. There was no significant deterioration over time of the mean postoperative air-bone gap for any frequency. CONCLUSION: Cumulative data from several authors show that -50% of patients undergoing partial ossiculoplasty have a postoperative air-bone gap of 0 to 10 dB, and 80% have a postoperative air-bone gap of 0 to 20 dB. Equally good results may be achieved with autograft (no difference was found between interposition of the incus or the head of the malleus), homograft, or alloplastic partial prostheses. With alloplastic total prostheses, 36% of patients have a postoperative air-bone gap of 0 to 10 dB, and 74% have a postoperative air-bone gap of 0 to 20 dB.

Cochlear morphology from Würzburg (1951) to Turin (1987): old and new aspects.

A review is given of the methods employed in human temporal bone pathology, from the camera lucida drawings of the last century to the sophisticated techniques of today.

Functional histopathology of the human audio-vestibular organ. Euro-Data-Hearing.

The present paper describes the setting-up of a new project, sponsored by the Commission of the European Communities, to promote the study of functional histopathology of the human audio-vestibular organ. The project has the purpose of co-ordinating in Europe morphological research on the hearing and equilibrium organ and promoting the comparison of data from clinical, physiological and morphological studies in the field of hearing and equilibrium impairment. A manual (Iurato et al., 1982) has been prepared with the objectives of (1) stimulating clinicians to participate in the project, (2) encouraging the collection of audiological data for comparison with pathology, and (3) supplying clinicians with the necessary information about the technique of fixation and preparation of the specimens. The fixation procedures for the two major techniques of studying ear pathology: (1) microdissection and electron microscopy, and (2) embedding of the whole block for serial sectioning and light microscopy, are described in detail. Special paragraphs deal with the technique of fixation of the brain and with the technique of removal of the temporal bones and brain at autopsy. The instructions for delivery of the specimens and the publication rules are enclosed in the main body of the manual. Appendix 1 contains a list of the participating laboratories. Appendix 2 deals with autopsy legislation in the different European countries. Appendix 3 contains the sender's data sheet which supplies the instructions for collecting the clinical history of the patient and the audiological and vestibular data.

Metaplasic bone tissue in tympanosclerosis.

Two different tissues have been observed in specimens of tympanosclerotic material studied under light and electron microscopy. The first, devoid of cells and blood vessels, is a dense fibrous tissue similar to that already described in fibrous tympanosclerosis. The second resembles a bone tissue, containing osteocytes and vascular channels; it is laid down by metaplasic fibroblasts following the invasion of the first tissue by osteoclasts and blood vessels after its calcification.

Freeze-fracture study of the cell junctions in the utricle and saccule.

The maculae sacculi and utriculi of the chinchilla vestibular labyrinth have been studied by freeze-fracture method. In the replicas extensive zonulae occludentes have been found between sensory and supporting cells at the endolymphatic surface. Gap junctions are located between the supporting cells. Some intramembranous specializations of the synaptic regions are described in both types of the sensory cells.

Intercellular junctions in the organ of Corti as revealed by freeze fracturing.

The junctions between the cells of the organ of Corti have been investigated with the freeze-fracture method in the chinchilla inner ear. Numerous gap junctions have been found among all the supporting cells, particularly at the level of their basal part. This means that the supporting cells have their cytoplasm electrotonically and metabolically coupled. Gap junctions were not observed between supporting and sensory cells nor between sensory cells and nerve endings. At this level the transmission should be chemically mediated.

[Connection complex on the cells of Reissner's membrane in freeze-fractured preparations]. / Verbindungskomplexe an zellen der reissner-membran in gefriergebrochenen präparaten

The Reissner membrane of the chinchilla inner ear was studied with the freeze-fracture method. Zonulae occludentes, composed of 2 to 8 strands, seal the intercellular space close to the endolymphatic surface. They are morphologically simialr to those seen between the marginal cells of the stri vascularis, but much less developed than those between the basal strial cells.

Histopathology of spontaneous brain herniations into the middle ear.

Two patients with spontaneous brain herniation into the middle ear have been operated on with a combined otoneurological approach. In case No. 1, two 2 x 3 mm arachnoid tissue herniations were found in the tegmen antri of the left ear. Six years later, a 8 x 9 mm mass consisting of prolapsed brain was removed from the right ear. The histological examination showed normal but disorganized nervous tissue. The surface consisted of middle ear mucosa or modified glial cells. More deeply numerous well preserved neurons and synapses were observed. In case No. 2, a 2 x 1 cm herniation was found in contact with the ossicles and the bony walls of the middle ear. The herniation consisted of partly degenerated nervous tissue which could explain the episode of temporal lobe seizure the patient experienced 8 years before surgery. In the world literature during the last 40 years, 29 cases of spontaneous or idiopathic brain herniation into the middle ear and mastoid have been reported. In 10, the herniations were multiple, as in our case No. 1. Case No. 1 is interesting also because the spontaneous brain herniation was bilateral.

[Clinical study of the efficacy and tolerability of nimesulide in suppositories compared to flurbiprofen in gynecology]. / Studio clinico sull'efficacia e la tollerabilità della nimesulide in formulazione supposte in confronto al flurbiprofen in ginecologia.

The efficacy and tolerability of nimesulide in a new pharmaceutical suppository form were assessed in a double blind study versus flurbiprofen in pain-inflammatory pathologies of obstetrico-gynecological nature. One hundred patients with pelvic inflammatory disease were randomly assigned to treatment with nimesulide or flurbiprofen. Both drugs, administered in a dose of 2 suppositories a day for 7 days, evidenced speedy, effective analgesic and anti-inflammatory activity combined with good tolerability. Specifically, as regards the pain component, nimesulide demonstrated a significantly more marked analgesic effect than flurbiprofen in the first two hours of treatment.