Early maladaptive schemas and behavioural addictions: a systematic literature review

As observed in other mental health difficulties, behavioural addiction is a complex construct with several potential predisposing factors, which include biological factors (e.g., genetic predispositions), psychological factors (e.g., personality traits), and social factors (e.g., family, and social history). One factor that may play a significant role in both developing and perpetuating behavioural addiction is the activation of early maladaptive schemas (EMSs). The aim of the present review was to synthesize the evidence concerning the relationship between behavioural addiction and EMSs. A comprehensive literature search using keywords and subject headings was performed with three electronic databases, resulting in 20 studies that met the inclusion criteria. In relation to specific behavioural addiction, the 20 studies examined: binge-eating/food addiction (n = 6), sexual addiction/compulsive sexual behaviours (n = 3), multiple addictive behaviours (n = 2), internet addiction (n = 2), smartphone addiction (n = 2), social networking/Facebook addiction (n = 2), exercise dependence (n = 1), gambling (n = 1), and videogame addiction (n = 1). The patterns of association between EMS and behavioural addiction were examined in both clinical and non-clinical population. The ‘Disconnection and Rejection’ domain was the most strongly related schema domain across all addictive behaviours, followed by ‘Impaired Limits’. The present review suggests a positive relationship between schema activation and several addictive behaviours, including addictions to gambling, gaming, social media use sex, exercise, and food. The clinical implications of the findings are discussed, but further research is needed to inform treatment plans and interventions for those who struggle with behavioural addictions

A novel cardiovascular magnetic resonance risk score for predicting mortality following surgical aortic valve replacement

The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00930735 and ClinicalTrials.gov Identifier: NCT01755936

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

A rare genomic duplication in 2p14 underlies autosomal dominant hearing loss DFNA58

Here we define a ~ 200Kb genomic duplication in 2p14 as the genetic signature that segregates with post-lingual progressive sensorineural autosomal dominant hearing loss in 20 affected individuals from the DFNA58 family, first reported in 2009. The duplication includes two entire genes, PLEK and CNRIP1, and the first exon of PPP3R1 (protein-coding), in addition to four uncharacterized long noncoding (lnc) RNA genes and part of a novel protein-coding gene. Quantitative analysis of mRNA expression in blood samples revealed selective overexpression of CNRIP1 and of two lncRNA genes (LOC107985892 and LOC102724389) in all affected members tested, but not in unaffected ones. Qualitative analysis of mRNA expression identified also fusion transcripts involving parts of PPP3R1, CNRIP1 and an intergenic region between PLEK and CNRIP1, in the blood of all carriers of the duplication, but were heterogeneous in nature. By in situ hybridization and immunofluorescence, we showed that Cnrip1, Plek and Ppp3r1 genes are all expressed in the adult mouse cochlea including the spiral ganglion neurons, suggesting changes in expression levels of these genes in the hearing organ could underlie the DFNA58 form of deafness. Our study highlights the value of studying rare genomic events leading to hearing loss such as copy number variations. Further studies will be required to determine which of these genes, either coding proteins or non-coding RNAs, is or are responsible for DFNA58 hearing loss

Intra-arterial chemoradiation for T3-4 oral cavity cancer: Treatment outcomes in comparison to oropharyngeal and hypopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Surgery followed by radiotherapy is the standard of care for resectable locally advanced oral cavity squamous cell carcinoma (SCC). We report the treatment outcomes of patients with T3-T4 SCC of the oral cavity treated with chemoradiation, an alternative approach.</p> <p>Patients and methods</p> <p>From a series of 240 patients with stage III-IV carcinoma of the upper aerodigestive tract who were treated consecutively according to the RADPLAT protocol, a subset analysis of 155 patients with T3-T4 SCC (Oral cavity SCC N = 22, oropharynx SCC N = 94 and hypopharynx SCC N = 39), was performed. The goal was to test the hypothesis that oral cavity SCC treated with chemoradiation has similar outcomes to the two comparison sites.</p> <p>Results</p> <p>With a median follow-up of 58 months, local disease control was 69% and the overall survival was 37%. In comparison, local disease control for the oropharynx and hypopharynx groups was 86% and 79% respectively. The overall survival rate for the oropharyngeal and hypopharyngeal groups were 41% and 6% respectively</p> <p>Conclusion</p> <p>Patients with locally advanced oral cavity cancer treated with the chemoradiation protocol RADPLAT have outcomes that are equal or better compared to patients with similar disease involving the oropharynx and hypopharynx</p

Otodental syndrome

The otodental syndrome also named otodental dysplasia, is characterised by a striking dental phenotype known as globodontia, associated with sensorineural high frequency hearing loss and eye coloboma. Globodontia occurs in both primary and permanent dentition, affecting canine and molar teeth (i.e. enlarged bulbous malformed posterior teeth with almost no discernable cusps or grooves). The condition appears to be inherited in an autosomal dominant mode, although sporadic cases have been reported. It is a rare disease, a few families have been described in the literature. In the British family, the locus for oculo-oto-dental syndrome was mapped to 20q13.1 within a 12-cM critical chromosomal region. Dental management is complex, interdisciplinary and will include regular follow up, scheduled teeth extraction and orthodontic treatment. Hearing checks and, if necessary, hearing aids are mandatory, as well as eye examination and ad hoc treatment if necessary