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Persons with intellectual disabilities (ID) are at increased risk for hearing impairment which often remains undetected. If left untreated, such hearing impairments may worsen the social and communicative problems of these persons. The aims of this study are to determine the prevalence of hearing impairment, to specify type and degree of hearing loss, and to evaluate the sensitivity and specificity of the screening in this population.During the German Special Olympics Summer Games 2006, 552 athletes with ID had their hearing screened according to the international protocol of Healthy Hearing, Special Olympics. This screening protocol includes otoscopy, measurement of distortion product otoacoustic emissions, and - if necessary - tympanometry and pure tone audiometry (PTA) screening at 2 and 4 kHz. Additionally, 195 athletes underwent a full diagnostic PTA. The results of the screening and diagnostic PTA were compared.Of the 524 athletes who completed the screening protocol, 76% passed and 24% failed it. Ear wax was removed in 48% of all athletes. 42% of the athletes were recommended to consult an otolaryngologist or an acoustician. Of the 99 athletes whose screening-based suspicion of a hearing loss was confirmed with diagnostic PTA, 74 had an undetected hearing loss. The correlation (Cramer's V) between screening and diagnostic PTA was .98. The sensitivity of the screening was 100% and the specificity 98%.The screening reliably detects hearing disorders among persons with ID. The prevalence of hearing impairment in this population is considerably higher than in the general population, and the proportion of undetected hearing impairments is large, even among people with only mild and moderate ID, as examined in this study. Therefore, a screening is highly recommended, and special attention from caregivers and professionals as well as regular hearing assessment and standard therapy programmes are required for persons with ID.

The production of biodegradable polymers in transgenic plants is an important challenge in plant biotechnology; nevertheless, it is often accompanied by reduced plant fitness. In order to decrease the phenotypic abnormalities caused by cytosolic production of the biodegradable polymer cyanophycin, and to increase polymer accumulation, four translocation pathway signal sequences for import into chloroplasts were individually fused to the coding region of the cyanophycin synthetase gene (cphA(Te)) of Thermosynechococcus elongatus BP-1, resulting in the constructs pRieske-cphA(Te), pCP24-cphA(Te), pFNR-cphA(Te) and pPsbY-cphA(Te). These constructs were expressed in Nicotiana tabacum var. Petit Havana SRI under the control of the constitutive cauliflower mosaic virus (CaMV) 35S promoter. Three of the four constructs led to polymer production. However, only the construct pPsbY-cphA(Te) led to cyanophycin accumulation exclusively in chloroplasts. In plants transformed with the pCP24-cphA(Te) and pFNR-cphA(Te) constructs, water-soluble and water-insoluble forms of cyanophycin were only located in the cytoplasm, which resulted in phenotypic changes similar to those observed in plants transformed with constructs lacking a targeting sequence. The plants transformed with pPsbY-cphA(Te) produced predominantly the water-insoluble form of cyanophycin. The polymer accumulated to up to 1.7% of dry matter in primary (T(0)) transformants. Specific T(2) plants produced 6.8% of dry weight as cyanophycin, which is more than five-fold higher than the previously published value. Although all lines tested were fertile, the progeny of the highest cyanophycin-producing line showed reduced seed production compared with control plants.

The International Association of Logopedics and Phoniatrics (IALP) assessed the therapy status of fluency disorders, service opportunities, and education of logopedists (speech-language pathologists) with a mail survey in Eastern Europe. Information was collected on the following aspects: incidence, prevalence, availability of information, non-therapeutic support for persons who stutter (PWS), providers of diagnostics and therapy, cooperating professionals, therapy approaches, forms, goals, financing, early detection and prevention, training of professionals, specialization in stuttering therapy, needs for improving the situation of PWS, and problems which hinder better care. Stuttering therapy for children is available in many countries and is frequently provided by the educational system. Therapy for adults is provided best by the health services but is not satisfactorily available everywhere. Modern therapeutic approaches coexist with obsolete ones. Lack of resources, awareness, entitlement, and assessment of therapy effectiveness are pervasive problems. Educational objectives: Readers will be able to describe and evaluate: (1) the therapy status of fluency disorders and service opportunities in various East-European countries; (2) the training of logopedists (speech-language pathologists); (3) specialization in stuttering therapy; and (4) the organizational services for PWS within the health and human service systems.

Leukocyte adhesion and transmigration are central features governing immune surveillance and inflammatory reactions in body tissues. Within the liver sinusoids, chemokines initiate the first crucial step of T-cell migration into the hepatic tissue. We studied molecular mechanisms involved in endothelial chemokine supply during hepatic immune surveillance and liver inflammation and their impact on the recruitment of CD4(+) T cells into the liver. In the murine model of Concanavalin A-induced T cell-mediated hepatitis, we showed that hepatic expression of the inflammatory CXC chemokine ligands (CXCL)9 and CXCL10 strongly increased whereas homeostatic CXCL12 significantly decreased. Consistently, CD4(+) T cells expressing the CXC chemokine receptor (CXCR)3 accumulated within the inflamed liver tissue. In histology, CXCL9 was associated with liver sinusoidal endothelial cells (LSEC) which represent the first contact site for T-cell immigration into the liver. LSEC actively transferred basolaterally internalized CXCL12, CXCL9 and CXCL10 via clathrin-coated vesicles to CD4(+) T cells leading to enhanced transmigration of CXCR4(+) total CD4(+) T cells and CXCR3(+) effector/memory CD4(+) T cells, respectively in vitro. LSEC-expressed CXCR4 mediated CXCL12 transport and blockage of endothelial CXCR4 inhibited CXCL12-dependent CD4(+) T-cell transmigration. In contrast, CXCR3 was not involved in the endothelial transport of its ligands CXCL9 and CXCL10. The clathrin-specific inhibitor chlorpromazine blocked endothelial chemokine internalization and CD4(+) T-cell transmigration in vitro as well as migration of CD4(+) T cells into the inflamed liver in vivo. Moreover, hepatic accumulation of CXCR3(+) CD4(+) T cells during T cell-mediated hepatitis was strongly reduced after administration of chlorpromazine. These data demonstrate that LSEC actively provide perivascularly expressed homeostatic and inflammatory chemokines by CXCR4- and clathrin-dependent intracellular transport mechanisms thereby contributing to the hepatic recruitment of CD4(+) T-cell populations during immune surveillance and liver inflammation.

The production of biodegradable polymers in transgenic plants in order to replace petrochemical compounds is an important challenge for plant biotechnology. Polyaspartate, a biodegradable substitute for polycarboxylates, is the backbone of the cyanobacterial storage material cyanophycin. Cyanophycin, a copolymer of l-aspartic acid and l-arginine, is produced via non-ribosomal polypeptide biosynthesis by the enzyme cyanophycin synthetase. A gene from Thermosynechococcus elongatus BP-1 encoding cyanophycin synthetase has been expressed constitutively in tobacco and potato. The presence of the transgene-encoded messenger RNA (mRNA) correlated with changes in leaf morphology and decelerated growth. Such transgenic plants were found to produce up to 1.1% dry weight of a polymer with cyanophycin-like properties. Aggregated material, able to bind a specific cyanophycin antibody, was detected in the cytoplasm and the nucleus of the transgenic plants.

The decision to mandate, finance, and implement a universal newborn hearing screening (UNHS) requires the evaluation of its therapy-directed benefit by comparing (1) a procedure employing a UNHS with (2) a targeted screening for at-risk babies for neonatal hearing disorders and (3) a procedure without systematic screening. In a cohort study the outcome of the UNHS program of Hessen in 2005 with 17,439 screened newborns was analyzed. Validity, effectiveness, and efficiency were evaluated and compared to a sample of 98 Hessian and 355 German children who were detected in 2005 as hearing-impaired but not by an UNHS. The UNHS group had a PASS rate of 97.0%. Forty-nine hearing-impaired children were diagnosed at a median age of 3.1 months and treated at a median age of 3.5 months. Corresponding values for the Hessian non-UNHS group were 17.8 and 21.0 months. For Germany the median age at diagnosis was 39.0 months. The age at therapy onset correlated negatively with parameters of speech/language and psychosocial development. A targeted screening would have resulted in a low sensitivity of 65.3%. Hence, a UNHS is the most effective way to an early therapy of neonatal hearing disorders with an optimal outcome.

Among persons with intellectual disability, the prevalence of hearing impairments is high. During the German Special Olympics Summer Games 2004, a hearing screening was conducted on 755 athletes with intellectual disabilities. Obligatory screening included ear inspection and recording of otoacoustic emissions, and optional screening included tympanometry and brief pure-tone audiometry. 38.0% of the athletes failed the screening. 53.0% needed ear wax removal. 56.1% of the fails indicated sensorineural hearing loss and 13.6% indicated mixed hearing loss. 12.5% of the fails were caused by unremovable ear wax, 1.4% by ear canal affections, and 16.4% by middle ear problems. Left ear fails were more frequent than right ear fails. A peripheral hearing disturbance can thus be expected in every third subject. The high failure rate, a considerable percentage of previously undetected profound hearing loss (1.1%), and the frequent need for ear wax removal, suggest that nearly half of persons with intellectual disabilities need regular otological or audiological consultations.

This article reviews some of our recent functional magnetic resonance imaging (fMRI) studies of stuttering. Using event-related fMRI experiments, we investigated brain activation during speech production. Results of three studies comparing persons who stutter (PWS) and persons who do not stutter (PWNS) are outlined. Their findings point to a region in the right frontal operculum (RFO) that was consistently implicated in stuttering. During overt reading and before fluency shaping therapy, PWS showed higher and more distributed neuronal activation than PWNS. Immediately after therapy differential activations were even more distributed and left sided. They extended to frontal, temporal, and parietal regions, anterior cingulate, insula, and putamen. These over-activations were slightly reduced and again more right sided two years after therapy. Left frontal deactivations remained stable over two years of observation, and therefore possibly indicate a dysfunction. After therapy, we noted higher activations in persons who stutter moderately than in those who stutter severely. These activations might reflect patterns of compensation. We discuss why these findings suggest that fluency-inducing techniques might synchronize a disturbed signal transmission between auditory, speech motor planning, and motor areas.The reader will learn about and be able to: (1) identify regions of brain activations and deactivations specific for PWS; (2) describe brain activation changes induced by fluency shaping therapy; and (3) discuss the correlation between stuttering severity and brain activation.

Rapid subglottal pressure changes related to the glottal cycles influence the aerodynamics of phonation. Various methods to measure these have been developed, but are not practical for routine phoniatric use. For that reason, a noninvasive measurement tool is necessary. This article presents a technique that uses a microphone positioned at the skin of the jugular fossa to record the signal which arises in the subglottal spaces and is transmitted through the soft tissue to the surface of the skin. Using the program Glottal Segmentation of Voice and Speech, jugular microphone recordings from two healthy subjects were compared with simultaneously recorded direct intratracheal measurements during the same phonation. A systematic error arising from the transmission properties of the microphone and the soft tissue leads to phase and amplitude deviations. These must be taken into account and require correction. This correction procedure leads to high correlations and a good agreement between the two signals. Even without this correction the jugular microphone measurements proved to be useful as a diagnostic and a therapeutic tool in cases where chest resonance specific processes appear affected. In addition, they offer material for research purposes. Although based on a small number of subjects, the new method shows a good validity; testing on a larger number of subjects will probably strengthen the validity.

Alport syndrome (AS) is a hereditary nephropathy with hematuria progressing to end-stage renal failure (ESRF), sensorineural deafness, and specific eye signs (lenticonus, macular flecks, and congenital cataracts). Inheritance is X-linked in about 85% of the cases, caused by different mutations in the COL4A5 gene. Rarely AS is seen in combination with diffuse leiomyomatosis (DL). DL is a tumorous process involving smooth muscle cells, mostly of the esophagus, but also of the tracheobronchial tree and the female genital tract. Characteristically, the patients have deletions of the 5'-end of both the COL4A5 and the COL4A6 genes, respectively. We here present a 9-year-old boy who was admitted because of a newly diagnosed sensorineural deafness. He was born with cataracts and presented symptoms of dysphagia and bronchial irritation in the first year of life. Macroscopic hematuria was first noticed at 2 years during a febrile infection. Since early childhood the boy suffered from severe constipation. Taking together these symptoms, the diagnosis of Alport syndrome with diffuse leiomyomatosis (AS-DL) has to be considered. Genetic analysis demonstrated the predicted deletion of the COL4A5/COL4A6 genes.

There is recent evidence of focal alteration in fibre tracts underlying the left sensorimotor cortex in persistent developmental stuttering (PDS) [Lancet 360 (2002) 380]. If, as proposed, this anatomical abnormality is the cause of PDS, then overactivation in the right hemisphere seen with functional neuroimaging in stutterers may reflect a compensatory mechanism. To investigate this hypothesis, we performed two functional magnetic resonance imaging (fMRI) experiments. The first showed systematic activation of a single focus in the right frontal operculum (RFO) in PDS subjects during reading, which was not observed in controls. Responses in this region were negatively correlated with the severity of stuttering, suggesting compensation rather than primary dysfunction. Negative correlation was also observed during the baseline task that consisted in passive viewing of meaningless signs, indicating that RFO compensation acts independently of specific demands on motor speech output. The second experiment, that involved a covert semantic decision task, confirmed that RFO activation does not require overt utterances or motor output. In combination these findings suggest that the RFO serves a nonspecific compensatory role rather than one restricted to the final stages of speech production.

A new, fast screening algorithm based on auditory brainstem response (ABR) recorded at a high click repetition rate is proposed. Response detection is carried out in the frequency domain by a statistical test procedure which includes the fundamental frequency and the harmonics below 800 Hz. First, the method was tested in 25 young adults. ABRs were recorded in the repetition rate range 20/s to 400/s. With a mean response detection time of 31 s, a click repetition rate of 140/s was found to be the optimum rate among the adult group. The method was then tested using a group of 114 neonates in whom the repetition rate range 60/s to 200/s was examined. At the repetition rate 90/s, which was found to be the optimum rate in neonates, the mean detection time was 24.6 s. In addition to the fast ABR detection, the proposed screening algorithm also allows simultaneous hearing screening of both ears using a one-channel data recording.

After 10 days of cultivation at 37°C, the herbicide resistance encoded by the chimaric pat41 gene (coding region from Streptomyces viridochromogenes fused to the 828bp CaMV35S promoter) was strongly reduced in 100% of the 27 independently transformed Nicotiana tabacum SRI lines analyzed. This reversible reduction occurred in sterile and unsterile culture in the first and second generation and even when the overnight temperature was reduced to 24°C. Neither the enzyme activity, the protein nor the pat41 specific RNA could be detected in the heat treated plants, regardless of the number of copies and the hemi -or homozygous state of the transgene. In contrast to this, the expression of the synthetic patS coding region fused to the 534 bp CaMV35S promoter and coding for essentially the same protein, was stable in heat treated plants. The exchange of the GC rich coding region of the pat41 gene by the AT rich synthetic DNA fragment carrying the patS coding region led to the stabilization of the specific RNA steady state level. However, the presence of the transgene-encoded protein at 37°C could only be achieved by the usage of the specific 5′ and 3′ untranslated regions present in the synthetic patS gene.

Actin-bundling Arabidopsis LIM proteins are subdivided into two subfamilies differing in their pH sensitivity. Widely-expressed WLIMs are active under low and high physiologically-relevant pH conditions, whereas pollen-enriched PLIMs are inactivated by pH values above 6.8. By a domain swapping approach we identified the C-terminal (Ct) domain of PLIMs as the domain responsible for pH responsiveness. Remarkably, this domain conferred pH sensitivity to LIM proteins, when provided “in trans” (i.e., as a single, independent, peptide), indicating that it operates through the interaction with another domain. An acidic 6xc-Myc peptide functionally mimicked the Ct domain of PLIMs and efficiently inhibited LIM actin bundling activity under high pH conditions. Together, our data suggest a model where PLIMs are regulated by an intermolecular interaction between their acidic Ct domain and another, yet unidentified, domain.