Mindfulness-Based Cognitive Therapy as a Treatment for Chronic Tinnitus: A Randomized Controlled Trial

BACKGROUND: Tinnitus is experienced by up to 15% of the population and can lead to significant disability and distress. There is rarely a medical or surgical target and psychological therapies are recommended. We investigated whether mindfulness-based cognitive therapy (MBCT) could offer an effective new therapy for tinnitus. METHODS: This single-site randomized controlled trial compared MBCT to intensive relaxation training (RT) for chronic, distressing tinnitus in adults. Both treatments involved 8 weekly, 120-min sessions focused on either relaxation (RT) or mindfulness meditation (MBCT). Assessments were completed at baseline and at treatment commencement 8 weeks later. The primary outcomes were tinnitus severity (Tinnitus Questionnaire) and psychological distress (Clinical Outcomes in Routine Evaluation - Non-Risk, CORE-NR), 16 weeks after baseline. The analysis utilized a modified intention-to-treat approach. RESULTS: A total of 75 patients were randomly allocated to MBCT (n = 39) or RT (n = 36). Both groups showed significant reductions in tinnitus severity and loudness, psychological distress, anxiety, depression, and disability. MBCT led to a significantly greater reduction in tinnitus severity than RT, with a mean difference of 6.3 (95% CI 1.3-11.4, p = 0.016). Effects persisted 6 months later, with a mean difference of 7.2 (95% CI 2.1-2.3, p = 0.006) and a standardized effect size of 0.56 (95% CI 0.16-0.96). Treatment was effective regardless of initial tinnitus severity, duration, or hearing loss. CONCLUSIONS: MBCT is effective in reducing tinnitus severity in chronic tinnitus patients compared to intensive RT. It also reduces psychological distress and disability. Future studies should explore the generalizability of this approach and how outcome relates to different aspects of the intervention

Exploring differential item functioning in the SF-36 by demographic, clinical, psychological and social factors in an osteoarthritis population

The SF-36 is a very commonly used generic measure of health outcome in osteoarthritis (OA). An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items work in the same way across subgroup of a population. That is, if respondents have the same 'true' level of outcome, does the item give the same score in different subgroups or is it biased towards one subgroup or another. Differential item functioning (DIF) can identify items that may be biased for one group or another and has been applied to measuring patient reported outcomes. Items may show DIF for different conditions and between cultures, however the SF-36 has not been specifically examined in an osteoarthritis population nor in a UK population. Hence, the aim of the study was to apply the DIF method to the SF-36 for a UK OA population. The sample comprised a community sample of 763 people with OA who participated in the Somerset and Avon Survey of Health. The SF-36 was explored for DIF with respect to demographic, social, clinical and psychological factors. Well developed ordinal regression models were used to identify DIF items. Results: DIF items were found by age (6 items), employment status (6 items), social class (2 items), mood (2 items), hip v knee (2 items), social deprivation (1 item) and body mass index (1 item). Although the impact of the DIF items rarely had a significant effect on the conclusions of group comparisons, in most cases there was a significant change in effect size. Overall, the SF-36 performed well with only a small number of DIF items identified, a reassuring finding in view of the frequent use of the SF-36 in OA. Nevertheless, where DIF items were identified it would be advisable to analyse data taking account of DIF items, especially when age effects are the focus of interest

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Epidermolysa bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene

BACKGROUND Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. RESULTS Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. CONCLUSIONS Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock

Desynchronization of Diurnal Rhythms in Bipolar Disorder and Borderline Personality Disorder

It has long been proposed that diurnal rhythms are disturbed in bipolar disorder (BD). Such changes are obvious in episodes of mania or depression. However, detailed study of patients between episodes has been rare and comparison with other psychiatric disorders rarer still. Our hypothesis was that evidence for desynchronization of diurnal rhythms would be evident in BD and that we could test the specificity of any effect by studying borderline personality disorder (BPD). Individuals with BD (n = 36), BPD (n = 22) and healthy volunteers (HC, n = 25) wore a portable heart rate and actigraphy device and used a smart-phone to record self-assessed mood scores 10 times per day for 1 week. Average diurnal patterns of heart rate (HR), activity and sleep were compared within and across groups. Desynchronization in the phase of diurnal rhythms of HR compared with activity were found in BPD (+3 h) and BD (+1 h), but not in HC. A clear diurnal pattern for positive mood was found in all subject groups. The coherence between negative and irritable mood and HR showed a four-cycle per day component in BD and BPD, which was not present in HC. The findings highlight marked de-synchronisation of measured diurnal function in both BD but particularly BPD and suggest an increased association with negative and irritable mood at ultradian frequencies. These findings enhance our understanding of the underlying physiological changes associated with BPD and BD, and suggest objective markers for monitoring and potential treatment targets. Improved mood stabilisation is a translational objective for management of both patient groups

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures

The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions. KCC2 dysfunction has been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described. Here we show recessive loss-of-function SLC12A5 mutations in patients with a severe infantile-onset pharmacoresistant epilepsy syndrome, epilepsy of infancy with migrating focal seizures (EIMFS). Decreased KCC2 surface expression, reduced protein glycosylation and impaired chloride extrusion contribute to loss of KCC2 activity, thereby impairing normal synaptic inhibition and promoting neuronal excitability in this early-onset epileptic encephalopathy

Availability of supplies and motivations for accessing voluntary HIV counseling and testing services in Blantyre, Malawi

<p>Abstract</p> <p>Background</p> <p>HIV counseling and testing is an important intervention in the prevention, control and management of the human immunodeficiency virus (HIV). Counseling and testing can be an entry point for prevention, care and support. Knowledge of the quality of services and motivations for testing by individuals is important for effective understanding of the testing environment.</p> <p>Methods</p> <p>A cross sectional explorative study of clients accessing HIV voluntary counseling and testing (VCT) and counselors was conducted in 6 government health centers in Blantyre City, Malawi. We aimed to assess the availability of critical clinic supplies and identify the motivations of clients seeking counseling and testing services. We also aimed to identify the health professional cadres that were providing VCT in Blantyre city.</p> <p>Results</p> <p>102 VCT clients and 26 VCT counselors were interviewed. Among the VCT clients, 74% were <=29 years, 58.8% were females and only 7% reported no formal education. 42.2% were single, 45.1% married, 8.8% widowed and 3.9% divorced or separated. The primary reasons for seeking HIV counseling and testing were: recent knowledge about HIV (31.4%), current illness (22.5%), self-assessment of own behavior as risky (15.5%), suspecting sexual partner's infidelity (13.7%) and seeking HIV confirmatory test (9.8%) and other reasons (6.9%). Of the 26 VCT counselors, 14 were lay volunteers, 7 health surveillance assistants and 5 nurses. All except one had been trained specifically for HIV counseling and testing. All 6 facilities were conducting rapid HIV testing with same day test results provided to clients. Most of the supplies were considered adequate for testing.</p> <p>Conclusion</p> <p>HIV counseling and testing facilities were available in Blantyre city in all the six public health facilities assessed. The majority of counseling and testing clients were motivated by perceptions of being at risk of HIV infection. In a country with 12% of individuals 15 to 49 years infected, there is need to encourage testing among population groups that may not perceive themselves to be at risk of infection.</p