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Background: Soft tissue preservation using a hydroxyapatite-coated abutment in bone conduction hearing implant surgery may lead to improved clinical outcomes over the short (1 year) and long term (3 years). Methods: In this open multi-center, randomized (1:1), controlled clinical trial, subjects with conductive, mixed hearing loss or single-sided sensorineural deafness were randomly assigned to receive the conventional intervention, a titanium abutment with soft tissue reduction surgery (control), or a new intervention, a hydroxyapatite-coated abutment with soft tissue preservation surgery (test). The primary efficacy outcome was the combined endpoint of numbness, pain, peri-abutment dermatitis, and soft tissue thickening/overgrowth after 1 and 3 years. Results: The Intention-to-treat (ITT) population consisted of 52 control subjects and 51 test subjects. The difference between the groups after 1 year of follow-up as measured by the primary efficacy outcome was not statistically significant ( p = 0.12) in the ITT population ( n = 103), but did reach statistical significance ( p = 0.03) in the per-protocol (PP) population ( n = 96). It showed an advantage for the test group, with over twice as many subjects (29%) without these medical events during the first year compared to the control group (13%). After 3 years, the difference between the two groups had declined and did not reach statistical significance (24 vs. 10%, ITT p = 0.45). Secondary outcome measures which showed a statistical significant difference during the first year, such as surgical time (15 vs. 25 minutes, p < 0.0001), numbness (90 vs. 69% of subjects experienced no numbness at 1 year, p < 0.01), neuropathic pain at 3 months ( p = 0.0087) and the overall opinion of the esthetic outcome (observer POSAS scale at 3 months, p < 0.01) were favorable for the test group. More soft tissue thickening/overgrowth was observed at 3 weeks for the test group ( p = 0.016). Similar results were achieved for the long term follow up. Conclusions: Soft tissue preservation with a hydroxyapatite-coated abutment leads to a reduction in the combined occurrence of complications over the first year which is not statistically significant in the ITT population but is in the PP population. This effect decreased for the long-term study follow up of 3 years and did also not reach statistical significance., (Copyright © 2020 van Hoof, Wigren, Ivarsson Blechert, Joore, Mateijsen, Bom, Stalfors, Eeg-Olofsson, Deguine, van der Rijt, Flynn, Algarra, Stokroos and the Angelfish Collaborative.)

Aim: To investigate the incidence of persisting auditory and vestibular sequelae in a group of 30 young adults recovering from Traumatic Brain Injury (TBI)., Methods: 30 participants, aged 21-45 years, with TBI suffered 19 months to 27 years previously, underwent a semi-structured interview and pure-tone hearing test in their home. Participants who failed the hearing screen then undertook a more comprehensive audiological evaluation., Results: A variety of sequelae to TBI were reported. These were interpreted as tinnitus (53%), vestibular dysfunction (83%), abnormal facial sensory symptoms (27%) and intolerance to loud/sudden noises (87%). Ten (33%) participants demonstrated significant sensorineural hearing impairment in addition to speech recognition performance significantly worse than would have been predicted from their hearing impairment., Conclusions: Findings from this study will be of benefit to health professionals working in this area of rehabilitation as they seek to provide functional assessments and devise programmes to treat the often devastating auditory processing problems of people recovering from TBI.

Cytokines and neuropeptides may be involved in seizure-associated processes. Following amygdala kindling in rats, we determined alterations of IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type I (IL-1RI), IL-1 receptor accessory proteins (IL-1R AcPs) I and II, TNF-alpha, TGF-beta1, neuropeptide Y (NPY), glycoprotein 130 (gp 130) and pro-opiomelanocortin (POMC) mRNA levels in the parietal, prefrontal and piriform cortices, amygdala, hippocampus and hypothalamus. Messenger RNAs expression in all brain regions was determined 2 h or 3 weeks following the last generalized convulsive seizure triggered from the ipsilateral kindled amygdala. The same brain region sample was used to assay for changes of all mRNA components. The results show that the 2 h-kindled group exhibited a significant up-regulation of IL-1beta, IL-1RI, TNF-alpha and TGF-beta1 mRNAs in all three cortical brain regions, amygdala and hippocampus. The largest up-regulation occurred in the prefrontal cortex (about 30-fold induction for IL-1beta and TNF-alpha mRNAs). IL-1R AcP I and II mRNA levels were also up-regulated in the cortical regions. No changes in IL-1beta, IL-1RI or TNF-alpha mRNA levels occurred in the 3 week-kindled group. NPY mRNA levels increased in the hippocampus, prefrontal and piriform cortices in the 2 h-kindled group, while IL-1Ra, gp 130, or POMC mRNA levels did not change in any group. The overall profile of mRNA changes shows specificity of transcriptional modulation induced by amygdala kindling. The data support a role of cytokines and NPY in the adaptive mechanisms associated with generalized seizure activity, with implications for neuroprotection, neuronal dysfunction and vulnerability associated with epileptic activity.

Physical (neurogenic) stressors may influence immune functioning and interleukin-1beta (IL-1beta) mRNA levels within several brain regions. The present study assessed the effects of an acute or repeated naturalistic, psychogenic stressor (predator exposure) on brain cytokine and neuropeptide mRNAs. Acute predator (ferret) exposure induced stress-like behavioral effects, including elicitation of a startle response and reduced exploratory behaviors; these responses diminished after 30 sessions. Moreover, acute and repeated predator exposure, like acute restraint stress, increased plasma corticosterone levels measured 5 min later, but not 2 h after stressor exposure. In contrast, none of the stressors used influenced IL-1beta, IL-1 receptor antagonist, IL-1 receptor type I, IL-1 receptor accessory proteins I and II, or tumor necrosis factor-alpha mRNA levels in the prefrontal cortex, amygdala, hippocampus, or hypothalamus. Likewise, there were no stressor effects on transforming growth factor-beta1, neuropeptide Y, glycoprotein 130, or leptin receptor mRNAs in brain regions. Thus, the naturalistic/psychogenic stressor used does not affect any of the brain cytokine component mRNAs studied. It is suggested that this type of stressor activates homeostatic mechanisms (e.g., glucocorticoid release), which act to preclude brain cytokine alterations that would otherwise favor neuroinflammatory/neuroimmunological responses and the consequent increase of brain sensitivity to neurotoxic and neurodegenerative processes.

Interferon-alpha (IFN-alpha) immunotherapy is associated with significant adverse neurological effects, including anorexia, which can be a limiting factor in immunotherapy. Thus, it is important to develop strategies that could ameliorate IFN-alpha-induced neurological manifestations without significantly affecting its immunomodulating properties. In this study, we tested the hypothesis that an endogenous feeding-enhancing peptide, neuropeptide Y (NPY), could inhibit IFN-alpha-induced anorexia in rats. The results show that IFN-alpha induced significant anorexia when administered centrally into the third cerebral ventricle at an immunotherapeutically relevant dose (1,350 IU/rat). Heat-inactivated IFN-alpha had no effect. NPY (5.0 microg/rat) counteracted the IFN-alpha-induced anorexia when administered 3 or 10 h following IFN-alpha, or when it was concomitantly administered with IFN-alpha. The data suggest that NPY and its agonists could represent a potential novel intervention for IFN-alpha immunotherapy-associated anorexia.

Neuropeptide Y (NPY), NPY 3-36 and pancreatic polypeptide (PP) increase short-term (2-h) food intake to varying degrees when given intracerebroventricularly (i.c.v.). Various Y receptor subtypes are proposed to participate in Y receptor ligand-induced stimulation of food intake. Here, we used an antisense phosphothio-oligodeoxynucleotide sequence (-5 relative to the initiating ATG) to the Y5 receptor subtype, which has been suggested to mediate NPY-induced feeding. Rats were treated with i.c.v. antisense or sense phosphothio-oligodeoxynucleotide for 3.5 days before NPY, NPY 3-36, or PP i.c.v. administration. The results show that antisense to the Y5 receptor had no effect on either spontaneous 2-h or NPY-, NPY 3-36-, or PP-stimulated 2-h food intake. However, there was a significant decrease relative to the sense control group in 10-h food intake following the initial 2-h feeding response to NPY (n = 10, p < 0.0001) or NPY 3-36 (n = 10, p < 0.05). The data suggest that the Y5 receptor has a modulatory role in the maintenance of feeding, but not as the critical receptor to confer for NPY and NPY 3-36 action on food intake.

By diminishing the role of communicative context, traditional tests of speech perception may underestimate or misrepresent the actual speech perception abilities of adults with a hearing impairment. This study investigates this contention by devising an assessment that may better simulate some aspects of "real-life" speech perception. A group of 31 participants with a severe-to-profound hearing impairment took part in a series of speech perception tests while wearing their hearing aids. The tests used question/answer or adjacency pairs, where the stimulus sentence was preceded by a question spoken by the participant. Four conditions were included: (a) where there was no initiating sentence, as in a traditional open-set speech perception test; (b) where the initiating question was neutral (e.g. "Why?"); (c) where there was a disruptive semantic relationship between the question and answer; and (d) where there was a strong contextual relationship between the question and answer. The time delay between the question and answer was also varied. Results demonstrated that in all conditions where there was a preceding question speech perception improved, and increasing the cohesion between the question and the reply improved speech perception scores. Additionally, time delay and the relatedness of the reply interacted. The effects of semantic context appeared to diminish over a 10-s period while other linguistic effects remained more constant. These results indicate the utility of simulating communicative environments within speech perception tests.

OB protein (leptin) decreases food intake in a variety of species. Here we investigated the effects of the intracerebroventricular administration of recombinant murine OB protein on food consumption and meal parameters in Wistar rats maintained ad libitum. The intracerebroventricular administration of OB protein (0.56-3.5 microg/rat) decreased feeding in a dose-dependent manner. Computer analysis of meal parameters demonstrated that OB protein (3.5 microg/rat, n = 10) decreased nighttime meal size by 42%, whereas meal frequency and meal duration were unaffected. Derived analyses for the nighttime also showed that OB protein decreased the feeding rate (meal size/meal duration) by 30%, whereas the satiety ratio (intermeal intervals/meal size) increased by 100%. A similar profile was observed during the daytime and total daily periods. The intracerebroventricular administration of heat-inactivated OB protein (3.5 microg/rat, n = 10) had no effect on any meal parameter. The results show that OB protein administered intracerebroventricularly inhibits feeding through a specific reduction of meal size.

Adults with severe or severe-to-profound hearing losses constitute between 11% and 13.5% of the hearing-impaired population. A detailed investigation of the speech recognition of adults with severe (n = 20) or severe-to-profound (n = 14) hearing loss was conducted at The University of Melbourne. Each participant took part in a series of speech recognition tasks while wearing his or her currently fitted hearing aid(s). The assessments included closed-set tests of consonant recognition and vowel recognition, combined with open-set tests of monosyllabic word recognition and sentence recognition. Sentences were presented in quiet and in noise at +10 dB SNR to replicate an environment more typical of everyday listening conditions. Although the results demonstrated wide variability in performance, some general trends were observed. As expected vowels were generally well perceived compared with consonants. Monosyllabic word recognition scores for both the adults with a severe hearing impairment (M = 67.2%) and the adults with a severe-to-profound hearing impairment (M = 38.6%) could be predicted from the segmental tests, with an allowance for lexical effects. Scores for sentences presented in quiet showed additional linguistic effects and a significant decrease in performance with the addition of background noise (from 82.9% to 74.1% for adults with a severe hearing loss and from 55.8% to 34.2% for adults with a severe-to-profound hearing loss). Comparisons were made between the participants and a group of adults using a multiple-channel cochlear implant. This comparison indicated that some adults with a severe or severe-to-profound hearing loss may benefit from the use of a cochlear implant. The results of this study support the contention that cochlear implant candidacy should not rely solely on audiometric thresholds.

Bacterial lipopolysaccharide (LPS) or endotoxin induces neurological manifestations including anorexia. It is proposed that LPS-induced cytokine production is involved in the generation of neurological manifestations and in neuroinflammatory/immunological responses during gram-negative infections. For example, LPS-induced effects can be blocked or ameliorated by the interleukin-1 receptor antagonist (IL-1Ra). Here, sensitive and specific RNase protection assays were used to investigate the effects of the intracerebroventricular (i.c.v.) administration of LPS on mRNA levels of interleukin-1beta (IL-1beta) system components, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and neuropeptide Y (NPY) in the cerebellum, hippocampus, and hypothalamus. The same brain region sample was analyzed with all of the antisense probes. The data show simultaneous local induction of multiple cytokine components messenger ribonucleic acids (mRNAs) within specific brain regions in anorectic rats responding to i.c.v. administered LPS (500 ng/rat). Interleukin-1beta and IL-1Ra had a similar mRNA induction profile (hypothalamus > cerebellum > hippocampus). Interleukin-1 receptor type I (IL-1RI) mRNA also increased in all three brain regions examined, and the soluble form of IL-1 receptor accessory protein (IL-1R AcP II) mRNA was induced in the hypothalamus. Tumor necrosis factor-alpha mRNA levels increased in the hypothalamus > hippocampus > cerebellum. Levels of membrane bound IL-1R AcP, TGF-beta1, and NPY mRNAs did not change significantly in any brain region. The results suggest that: (1) endogenous up-regulation of IL-1beta and TNF-alpha in the hypothalamus contribute to LPS-induced anorexia; and (2) the ratio IL-1Ra/IL-1beta, and IL-1beta <--> TNF-alpha interactions may have implications for gram-negative infections associated with high levels of LPS in the brain-cerebrospinal fluid.

As a component of a pretraining investigation of the moral knowledge of 100 mentally handicapped adults (56 females, 44 males), the spontaneous definitions of 'good' and 'bad' acts were acquired. The results suggest that these concepts are predominantly consequence oriented and that mentally handicapped adults experience confusion in the use of these two terms.

This paper reports an investigation to determine whether staff in an Adult Training Centre could estimate the performance of adults who are mentally handicapped on a test of moral knowledge. It also sought to discover whether estimations are more accurate in instances where staff claim to have a closer knowledge of the subjects. Not only do the results indicate that training staff are unable to estimate accurately, but they overestimate knowledge in this subject area. The degree of knowledge of the subjects made no difference to the accuracy of staff estimations. The implications of these results are considered in terms of the training needs of staff in Adult Training Centre and the use of assessment criteria prior to the entry of students into specific training programmes.

This study describes the circumstances of 12 adults who are mentally handicapped who are residing with their parents. The results are derived from a content analysis of interviews. The analysis explores the reliability of a procedure for rating people's satisfaction. It also investigates people's views regarding the following: money, cooking, laundry, shopping, cleaning, home, neighbours, friends, support, interests and the ATC.

This paper has arisen from an investigation of the lives and circumstances of 88 people who are mentally handicapped and living in their own homes or tenancies. This study is funded by the Economic and Social Research Council. The difficulties inherent in interviewing people who are mentally handicapped are outlined. This is followed by a consideration of the findings of previous research and a listing of guidelines for interviewing. The paper also explores consent procedures and issues pertaining to the measurement of satisfaction.