Antisense oligonucleotides restore excitability, GABA signalling and sodium current density in a Dravet syndrome model.

Dravet syndrome is an intractable developmental and epileptic encephalopathy caused by de novo variants in SCN1A resulting in haploinsufficiency of the voltage-gated sodium channel Nav1.1. We showed previously that administration of the antisense oligonucleotide STK-001, also called ASO-22, generated using targeted augmentation of nuclear gene output technology to prevent inclusion of the nonsense-mediated decay, or poison, exon 20N in human SCN1A, increased productive Scn1a transcript and Nav1.1 expression and reduced the incidence of electrographic seizures and sudden unexpected death in epilepsy in a mouse model of Dravet syndrome. Here, we investigated the mechanism of action of ASO-84, a surrogate for ASO-22 that also targets splicing of SCN1A exon 20N, in Scn1a+/- Dravet syndrome mouse brain. Scn1a +/- Dravet syndrome and wild-type mice received a single intracerebroventricular injection of antisense oligonucleotide or vehicle at postnatal Day 2. We examined the electrophysiological properties of cortical pyramidal neurons and parvalbumin-positive fast-spiking interneurons in brain slices at postnatal Days 21-25 and measured sodium currents in parvalbumin-positive interneurons acutely dissociated from postnatal Day 21-25 brain slices. We show that, in untreated Dravet syndrome mice, intrinsic cortical pyramidal neuron excitability was unchanged while cortical parvalbumin-positive interneurons showed biphasic excitability with initial hyperexcitability followed by hypoexcitability and depolarization block. Dravet syndrome parvalbumin-positive interneuron sodium current density was decreased compared to wild-type. GABAergic signalling to cortical pyramidal neurons was reduced in Dravet syndrome mice, suggesting decreased GABA release from interneurons. ASO-84 treatment restored action potential firing, sodium current density and GABAergic signalling in Dravet syndrome parvalbumin-positive interneurons. Our work suggests that interneuron excitability is selectively affected by ASO-84. This new work provides critical insights into the mechanism of action of this antisense oligonucleotide and supports the potential of antisense oligonucleotide-mediated upregulation of Nav1.1 as a successful strategy to treat Dravet syndrome.

Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.

Several integral membrane proteins undergo regulated intramembrane proteolysis (RIP), a tightly controlled process through which cells transmit information across and between intracellular compartments. RIP generates biologically active peptides by a series of proteolytic cleavage events carried out by two primary groups of enzymes: sheddases and intramembrane-cleaving proteases (iCLiPs). Following RIP, fragments of both pore-forming and non-pore-forming ion channel subunits, as well as immunoglobulin super family (IgSF) members, have been shown to translocate to the nucleus to function in transcriptional regulation. As an example, the voltage-gated sodium channel ß1 subunit, which is also an IgSF-cell adhesion molecule (CAM), is a substrate for RIP. ß1 RIP results in generation of a soluble intracellular domain, which can regulate gene expression in the nucleus. In this review, we discuss the proposed RIP mechanisms of voltage-gated sodium, potassium, and calcium channel subunits as well as the roles of their generated proteolytic products in the nucleus. We also discuss other RIP substrates that are cleaved by similar sheddases and iCLiPs, such as IgSF macromolecules, including CAMs, whose proteolytically generated fragments function in the nucleus. Importantly, dysfunctional RIP mechanisms are linked to human disease. Thus, we will also review how understanding RIP events and subsequent signaling processes involving ion channel subunits and IgSF proteins may lead to the discovery of novel therapeutic targets. SIGNIFICANCE STATEMENT: Several ion channel subunits and immunoglobulin superfamily molecules have been identified as substrates of regulated intramembrane proteolysis (RIP). This signal transduction mechanism, which generates polypeptide fragments that translocate to the nucleus, is an important regulator of gene transcription. RIP may impact diseases of excitability, including epilepsy, cardiac arrhythmia, and sudden death syndromes. A thorough understanding of the role of RIP in gene regulation is critical as it may reveal novel therapeutic strategies for the treatment of previously intractable diseases.

Subcellular dynamics and functional activity of the cleaved intracellular domain of the Na+ channel ß1 subunit.

The voltage-gated Na+ channel ß1 subunit, encoded by SCN1B, regulates cell surface expression and gating of α subunits and participates in cell adhesion. ß1 is cleaved by α/ß and γ-secretases, releasing an extracellular domain and intracellular domain (ICD), respectively. Abnormal SCN1B expression/function is linked to pathologies including epilepsy, cardiac arrhythmia, and cancer. In this study, we sought to determine the effect of secretase cleavage on ß1 function in breast cancer cells. Using a series of GFP-tagged ß1 constructs, we show that ß1-GFP is mainly retained intracellularly, particularly in the endoplasmic reticulum and endolysosomal pathway, and accumulates in the nucleus. Reduction in endosomal ß1-GFP levels occurred following γ-secretase inhibition, implicating endosomes and/or the preceding plasma membrane as important sites for secretase processing. Using live-cell imaging, we also report ß1ICD-GFP accumulation in the nucleus. Furthermore, ß1-GFP and ß1ICD-GFP both increased Na+ current, whereas ß1STOP-GFP, which lacks the ICD, did not, thus highlighting that the ß1-ICD is necessary and sufficient to increase Na+ current measured at the plasma membrane. Importantly, although the endogenous Na+ current expressed in MDA-MB-231 cells is tetrodotoxin (TTX)-resistant (carried by Nav1.5), the Na+ current increased by ß1-GFP or ß1ICD-GFP was TTX-sensitive. Finally, we found ß1-GFP increased mRNA levels of the TTX-sensitive α subunits SCN1A/Nav1.1 and SCN9A/Nav1.7. Taken together, this work suggests that the ß1-ICD is a critical regulator of α subunit function in cancer cells. Our data further highlight that γ-secretase may play a key role in regulating ß1 function in breast cancer.

Prevalence of gastrointestinal malignancy in non-anemic iron deficiency and significance for endoscopic screening: A Western Australian multicenter cohort study.

BACKGROUND AND AIM: There is a paucity of evidence regarding non-anemic iron deficiency as a predictor for colorectal cancer and therefore the indication for endoscopic evaluation. This study explores the rates of malignancy in adults with iron deficiency with and without anemia. METHODS: A retrospective multicenter diagnostic cohort study was conducted across two Australian health services. All cases that underwent both esophagogastroduodenoscopy and colonoscopy between September 1, 2018, and December 31, 2019, for the investigation of iron deficiency were included, and the cohort was divided into anemic and non-anemic arms. Multivariate binomial logistic regression was performed to establish clinical characteristics associated with neoplasia. RESULTS: Five hundred eighty-four patients underwent endoscopic evaluation over a 16-month period. There was a significantly higher rate of malignancy in the iron deficiency anemia arm as compared with those without anemia (8.76% vs 1.20%, P < 0.01). Gastrointestinal pathology to account for iron deficiency was identified in > 60% of the total cohort. The presence of anemia (odds ratio [OR] 6.87, P < 0.01) and male gender (OR 3.01, P = 0.01) were significant predictors of malignancy. CONCLUSION: This study demonstrates that anemic iron deficiency confers a significantly greater risk of gastrointestinal cancer compared with non-anemic iron deficiency. Additionally, over 60% of patients had gastrointestinal pathology to account for iron deficiency overall, supporting the need to perform baseline endoscopy in patients with iron deficiency.

The awareness and usage of orthodontic apps and social media by orthodontists in the UK: A questionnaire-based study.

OBJECTIVE: To assess the awareness and usage of mobile apps and social media among orthodontic clinicians to support patients with orthodontic treatment, support the professional development of orthodontists, and identify any relevant apps and social media platforms currently recommended to patients. DESIGN: Cross-sectional questionnaire-based study. SETTING: United Kingdom. METHODS: A questionnaire was developed and distributed to members of the British Orthodontic Society (BOS). To increase the response rate, the questionnaire was circulated at three time points between January and March 2020. RESULTS: A total of 149 orthodontists responded to the questionnaire (15% response rate) with 113 orthodontists completing all questions (11.4%). Of those who answered, 81% (n = 111) had been qualified for >10 years, 35% worked in practice (n = 48), 34% worked in a hospital (n = 47) and 26% worked in both hospital and practice (n = 36). The results indicated that 20% of clinicians (n = 22) used apps to support patients and 33% (n = 37) reported using apps for professional purposes. Brush DJ appeared to be the most popular patient focused app (39%, n = 18) whereas the IOTN (17%, n = 8), Invisalign (17%, n = 8) and Dental Monitoring apps (9%, n = 4) were the most popular clinician-focused apps. With regard to social media, 53% (n = 60) of respondents reported that they used social media to communicate generic orthodontic information and promote their practice to patients. The most commonly used social media platforms were Facebook and Instagram. Of respondents, 96% expressed a willingness to recommend an evidence-based mobile app to patients if available, and 88% were willing to recommend an evidence-based social media platform. CONCLUSIONS: Orthodontic clinicians are utilising mobile apps and social media to support both patients and their own professional development. There is a willingness to increase the use of evidence-based platforms and apps to support patients.

Multiple Early-Life Seizures Alters Neonatal Communicative Behavior in Fmr1 Knockout Mice.

Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and a significant contributor to Autism Spectrum Disorder. Individuals with FXS are subject to developing numerous comorbidities, one of the most prevalent being seizures. In the present study, we investigated how seizures affected neonatal communicative behavior in the FXS mouse model. On postnatal day (PD) 7 through 11, we administered 3 flurothyl seizures per day to both Fmr1 knockout and wild-type C57BL/6J male mice. Ultrasonic vocalizations were recorded on PD12. Statistically significant alterations were found in both spectral and temporal measurements across seizure groups. We found that induction of seizures across PD7-11 resulted in an increased fundamental frequency (pitch) of ultrasonic vocalizations produced (p < 0.05), a longer duration of calls (p < 0.05), and a greater cumulative duration of calls (p < 0.05) in both genotypes. Induction of seizures across PD7-11 also resulted in a decreased latency to the first emitted vocalization (p < 0.05) and a decrease in mean power (loudness) for their vocalizations (p < 0.05). Early-life seizures also resulted in an increase in the number of downward and frequency step call types (p < 0.05). There was a significant increase in the number of chevron calls emitted from the Fmr1 knockout mice that received seizures compared to knockout control and wild-type seizure mice (p < 0.05). Overall, this study provides evidence that early-life seizures result in communication impairments and that superimposing seizures in Fmr1 knockout mice does produce an additional deficit in vocalization.

Development of a checklist to assess COVID-19 information on orthodontic webpages.

OBJECTIVE: To create a COVID-19 information checklist and critique all available webpages of hospitals with an orthodontic department in England. DESIGN: Cross-sectional analysis. SETTING: World Wide Web. METHODS: A 16-item COVID-19 webpage checklist was developed using up-to-date COVID-19 government advice, and the General Dental Council Principles of Ethical Advertising. Presence of advice on managing orthodontic appliance breakages, information on outpatient appointment changes and video consultations was also assessed. The checklist was used to undertake a cross-sectional analysis of all available webpages of hospitals with an orthodontic department in England between September 2020 to October 2020. RESULTS: A total of 61 webpages were assessed. Of them, 95% had a COVID-19 section on the homepage, including advice on the use of face coverings during hospital visits. Only 18% of websites provided information on orthodontic appliance care and breakages. Four orthodontic department websites stated the department was closed during this study. The mean update interval of the webpages was six weeks (range = 1-28 weeks). Only one webpage fully conformed with the COVID-19 checklist. CONCLUSION: Availability and completeness of COVID-19 information on webpages of hospitals with an orthodontic department varied, which may be due to the absence of a formal COVID-19 information webpage checklist. The checklist produced in this research may prove valuable to encourage uniform patient support and positive patient experience across orthodontic services. Principles behind the development of the checklist could be adopted during prolonged service disruptions to ensure optimal patient communications. The checklist is equally applicable to primary and secondary care settings.

A vitamin D enriched diet attenuates sex-specific behavioral deficits, increases the lifespan, but does not rescue bone abnormalities in a mouse model of cortical dysplasia.

Individuals who experience recurrent spontaneous seizures often show behavioral and physiological comorbidities. Those with epilepsy are at a high risk of bone fractures (independent of seizure-related falls) and show a higher rate of a diagnosis of Autism Spectrum Disorder. The neural subset-specific (NS) Pten knockout (KO) mouse has an epilepsy phenotype, has been characterized to show autistic-like deficits, and has an osteoporosis phenotype. The current study examined the effect of a vitamin D enriched diet (20,000 IU VD) in the NS-Pten KO and wildtype mice. Mice were placed onto a vitamin D enriched diet at 4 weeks of age and maintained on that diet throughout testing. Behavioral testing began at 6 weeks of age and included tests for general activity, anxiety, repetitive behaviors, social behaviors, and memory. Results indicated that a vitamin D diet attenuated hypoactivity levels in male KO mice (p < 0.05). In a social partition task, vitamin D increased sociability in male wildtype mice, (p < 0.05). Most significantly, vitamin D fortified diet increased percent survival in KO animals and decreased the level of microglia marker IBA-1 and mTOR (mammalian target of rapamycin) downstream targets pS6 and pAKT. A high vitamin D diet did not reverse bone deficits in male or female KO mice. Overall, these findings suggest that a vitamin D enriched diet had a significant impact on the behavioral phenotype of NS-Pten KO mice, suggesting that dietary manipulations could be a potential therapeutic option for autistic-like behavior.

Prenatal High-Fat Diet Rescues Communication Deficits in Fmr1 Mutant Mice in a Sex-Specific Manner.

Using high-throughput analysis methods, the present study sought to determine the impact of prenatal high-fat dietary manipulations on isolation-induced ultrasonic vocalization production in both male and female Fmr1mutants on postnatal day 9. Prior to breeding, male FVB/129 Fmr1 wildtype and female Fmr1 heterozygous breeding pairs were assigned to 1 of 3 diet conditions: standard lab chow, omega-3 fatty acid-enriched chow, and a diet controlling for the fat increase. Prenatal exposure to omega-3 fatty acids improved reductions in the number of calls produced by Fmr1heterozygotes females. Moreover, diminished spectral purity in the female Fmr1homozygous mouse was rescued by exposure to both high-fat diets, although these effects were not seen in the male Fmr1knockout. Prenatal dietary fat manipulation also influenced several other aspects of vocalization production, such as the number of calls produced and their fundamental frequency, aside from effects due to loss of Fmr1.Specifically, in males, regardless of genotype, prenatal exposure to high omega-3s increased the average fundamental frequency of calls. These data support the need for future preclinical and clinical work elucidating the full potential of prenatal high-fat diets as a novel therapeutic alternative forFragile X syndrome.

A single episode of early-life status epilepticus impacts neonatal ultrasonic vocalization behavior in the Fmr1 knockout mouse.

Fragile X syndrome (FXS) is a genetic disorder caused by a trinucleotide (CGG) expansion mutation in the Fmr1 gene located on the X chromosome. It is characterized by hyperactivity, increased anxiety, repetitive-stereotyped behaviors, and impaired language development. Many children diagnosed with FXS also experience seizures during their lifetime. However, the underlying etiology of the relationship between FXS and epilepsy is not fully understood. Ultrasonic vocalizations (UVs) are one tool that may be used to measure early behavioral changes in mouse pups. In the present study, neonatal UVs were analyzed as a measure of communicative behavior in a mouse model of FXS, both with and without early-life seizures (ELSs). On postnatal day (PD) 10, status epilepticus (SE) was induced via intraperitoneal injections of 0.5% kainic acid (2.0 mg/kg) in male Fmr1 knockout (KO) and wild-type (WT) mice. On PD 12, all pups were temporarily isolated from their dam and UVs were recorded. Significant alterations were found in both spectral and temporal measures across genotype and seizure groups. Early-life seizure experience resulted in a significant increase in the quantity of UVs only in WT animals (p < 0.05). We also found that while there was no difference between genotypes in the total number of vocalizations made, calls produced by Fmr1 KO mice were significantly shorter and had a higher peak frequency compared with WT mice. Overall, these findings support the use of vocalization behavior as an early phenotypic marker and highlight the importance of utilizing double-hit models to better understand comorbid disorders.

Sub-syndromal PTSD: what is important to know in military personnel and veterans?

OBJECTIVE: To assist healthcare professionals in their management of military personnel and veterans by providing information on the importance of sub-syndromal PTSD. CONCLUSION: Sub-syndromal PTSD occurs when persons experience many of the symptoms of PTSD, with some impairment, but do not meet full diagnostic criteria. Found to be associated with a range of mental health conditions including alcohol abuse, higher rates of suicidal ideas and delayed-onset PTSD, it should be seen as 'symptoms that are predictive of later disorder'. Patients with this condition need accurate assessment, trauma-focused therapy and follow-up to address the symptoms and, potentially, prevent development of PTSD.

An incidental dense bone island: A review of potential medical and orthodontic implications of dense bone islands and case report.

Dense bone islands (DBIs) are usually asymptomatic and do not require any treatment. This case report presents a DBI of an unusual presentation, which was an incidental finding on a radiograph of a 15-year-old orthodontic patient. The DBI lesion was 24 mm in size, occupying at least 50% of the alveolar process between the upper right canine and lateral incisor, extending up the lateral aspect of the anterior margin of the right nasal fossa. Generally, DBIs are 2-3 mm in size and more commonly found in the mandible in the molar and premolar region. This article further discusses the impact of DBIs on orthodontic treatment such as difficulty with achieving space closure and adequate root tip or torque. We also examine the potential medical implications of DBIs. This is clinically important, especially if multiple DBIs, or osteomas which have a similar radiographic appearance to DBIs, are found in a patient as they may be associated with adenomatous intestinal polyps, which, if not treated, have a 100% chance of becoming malignant transformation.

High seizure load during sensitive periods of development leads to broad shifts in ultrasonic vocalization behavior in neonatal male and female C57BL/6J mice.

There is increasing evidence that seizures during early development can impact ultrasonic vocalizations (USVs) emitted from neonatal mice. However, most of the effects of early-life seizures have been reported using chemoconvulsants that produce continuous seizures (status epilepticus). In the present study, we evaluated the impact of different seizure frequency loads during early-life vocalization development in C57BL/6J male and female mice. For the high seizure load (HSL) paradigm, we administered 3 flurothyl seizures to mice on postnatal day (PD) 7 through PD11, and recorded USVs on PD12. We found that the induction of seizures across PD7-11 resulted in increased average duration (P < 0.05) and cumulative duration (P < 0.05) of USVs across both sexes. Call-type analyses indicated several call-type changes, including reduced production of complex call-types from males' HSL condition. For the low seizure load (LSL) paradigm, we induced 3 flurothyl seizures only on PD10 and recorded USVs on PD12. We found no change in any spectral or temporal features of USVs. However, call-type production analyses indicated that both male and female animals from the LSL paradigm also produced changes in call-types. This study provides evidence that the magnitude of communication impairment following seizures is significantly impacted by seizure frequency load early in development.

Patient awareness of orthodontic mobile phone apps.

INTRODUCTION: Mobile phone applications (apps) can be engaging, accessible, versatile and have the potential to improve patient care. In 2017, 354 orthodontic apps were reported to be available, many of them targeted at patients; however, the awareness and usage of apps among orthodontic patients was unreported. AIM: The primary aim of this study was to assess patients' current awareness of orthodontic apps. METHODS: One hundred orthodontic patients (50 new and 50 in treatment) completed a questionnaire designed to explore their awareness, access to and utilisation of orthodontic apps and social media to support orthodontic treatment. Furthermore, their willingness to engage with and use an app to aid with orthodontic treatment was explored. There were no age restrictions or exclusion criteria. RESULTS: Ninety percent of patients had access to a smartphone, of which 73% belonged to them (rather than a parent/relative). Apple was the most popular platform (56%) followed by Android (26%). Only 7% of patients were aware that apps were available to help with orthodontic treatment and no patients had previously used an app related to orthodontics. However, 87% of patients stated that they would be willing to use an app to support treatment. Twenty-one percent of patients had previously looked up information on social media, with YouTube being the most popular platform. CONCLUSION: Current awareness of the availability of apps is poor, despite the finding that 87% of patients reported they would be willing to use an app to aid with orthodontic treatment. Given the availability of apps targeted at orthodontic patients, there is a need to assess the quality of these apps and, if appropriate, navigate patients towards high-quality, effective apps.

Availability of orthodontic smartphone apps.

OBJECTIVE: To identify and profile the available orthodontic smartphone apps published on the UK Apple App Store and Google Play Store. DESIGN: A review of available smartphone apps. SETTING: London, UK. METHODS: The Apple App Store and Google Play Store were accessed in October 2018; all orthodontic apps with a title and description available in English were included. Each app was classified according to the following criteria: name; target audience (patient or clinician); focus; platform (Apple App Store and/or Google Play Store); cost; rating and number of ratings; size; creation date; country of development and developer. RESULTS: A total of 305 orthodontic related apps were identified for inclusion. The majority of apps were aimed at patients (n = 241) and the most of these were focussed on gaming (n = 136), many apps were also found to be developed by specialist practices (n = 63) and to provide knowledge for patients (n = 56). Two hundred and ninety-five apps were free, with some of these including the option of paying for in-app purchases. Most apps were developed in the USA (n = 84). CONCLUSIONS: There has been an increase in the availability of orthodontic apps in recent years. The majority of available apps are patient-focused, most commonly games. A number of apps aim to elicit a behaviour change in our patients; therefore, there is a need to assess the quality and educational content of these.

Early-life status epilepticus acutely impacts select quantitative and qualitative features of neonatal vocalization behavior: Spectrographic and temporal characterizations in C57BL/6 mice.

Early-life seizures are known to cause long-term deficits in social behavior, learning, and memory, however little is known regarding their acute impact. Ultrasonic vocalization (USV) recordings have been developed as a tool for investigating early communicative deficits in mice. Previous investigation from our lab found that postnatal day (PD) 10 seizures cause male-specific suppression of 50-kHz USVs on PD12 in 129 SvEvTac mouse pups. The present study extends these findings by spectrographic characterization of USVs following neonatal seizures. On PD10, male C57BL/6 pups were administered intraperitoneal injections of kainic acid or physiological saline. On PD12, isolation-induced recordings were captured using a broad-spectrum ultrasonic microphone. Status epilepticus significantly suppressed USV quantity (p=0.001) and total duration (p<0.05). Seizure pups also utilized fewer complex calls than controls (p<0.05). There were no changes in call latency or inter-call intervals. Spectrographic analysis revealed increased peak amplitude for complex, downward, short, two-syllable, and upward calls, as well as reduced mean duration for short and two-syllable calls in seizure mice. This investigation provides the first known spectrographic characterization of USVs following early-life seizures. These findings also enhance evidence for USVs as an indicator of select communicative impairment.

Occlusal outcomes in combined orthodontic and orthognathic treatment.

OBJECTIVE: To investigate the treatment outcome in terms of the malocclusion features and the changes in the occlusion of patients undergoing orthodontic/orthognathic treatment using the Peer Assessment Rating (PAR) and the Index of Complexity, Outcome and Need (ICON) and to test the application of the Index of Orthognathic Functional Treatment Need (IOFTN) on this sample as a measure of orthognathic pre-treatment need. DESIGN: Retrospective longitudinal cohort study. SETTING: The orthodontic department at the Eastman Dental Hospital. MATERIAL AND METHODS: The study models of a sample of 100 orthodontic/orthognathic patients who were treated at the Eastman Dental Hospital were measured using the PAR index and ICON at three stages: pre-treatment, pre-surgery and at debond. Treatment need was assessed by measuring IOTN and IOFTN using start study models. RESULTS: 99% of the sample showed an improvement in PAR score, with 82% of the sample being greatly improved. ICON showed that 95% of the sample had an improvement of different degrees with 5% being not improved or worse. The IOFTN qualified 97% of the patients for orthognathic treatment when used retrospectively on the sample while the DHC of IOTN qualified the whole sample for orthodontic treatment. CONCLUSIONS: Orthodontic/orthognathic treatment showed improved and acceptable overall results. The PAR index and ICON were valid measures to investigate the outcome of orthognathic treatment. IOFTN proved to be a useful tool in determining and prioritizing orthognathic treatment based purely on functional need.

Neuropsychological findings associated with Panayiotopoulos syndrome in three children.

Panayiotopoulos syndrome is a common idiopathic benign epilepsy that has a peak age of onset in early childhood. The syndrome is multifocal and shows significant electroencephalogram (EEG) variability, with occipital predominance. Although a benign syndrome often refers to the absence of neurological and neuropsychological deficits, the syndrome has recently been associated with cognitive impairments. Also, despite frequent occipital EEG abnormalities, research regarding the visual functioning of patients is less reported and often contradictory. The purpose of this study was to gain additional knowledge regarding the neurocognitive functioning of patients with Panayiotopoulos syndrome and specifically to address any visual processing deficits associated with the syndrome. Following diagnosis of the syndrome based on typical clinical and electrophysiological criteria, three patients, aged 5, 8, and 10years were referred by epileptologists for neuropsychological evaluation. Neuropsychological findings suggest that the patients had notable impairments on visual memory tasks, especially in comparison with verbal memory. Further, they demonstrated increased difficulty on picture memory suggesting difficulty retaining information from a crowded visual field. Two of the three patients showed weakness in visual processing speed, which may account for weaker retention of complex visual stimuli. Abilities involving attention were normal for all patients, suggesting that inattention is not responsible for these visual deficits. Academically, the patients were weak in numerical operations and spelling, which both rely partially on visual memory and may affect achievement in these areas. Overall, the results suggest that patients with Panayiotopoulos syndrome may have visual processing and visual memory problems that could potentially affect their academic capabilities. Identifying such difficulties may be helpful in creating educational and remedial assistance programs for children with this syndrome, as well as developing appropriate presentation of information to these children in school.

An incidental finding of a long-standing button battery in the floor of the nose during a routine orthodontic examination.

Foreign body insertion into the ears and nose is common in children and is often witnessed by the carer or reported by the child and therefore appropriate management can be sought promptly. However, these incidents can go unreported and may be accompanied by non-specific symptoms making diagnosis difficult. Button batteries are common in everyday life and their small size and shiny appearance make them appealing to children and their ingestion or insertion is not uncommon. Due to their size, shape and electrochemical composition button batteries pose serious complications if ingested, inhaled or inserted. In the nose they usually cause intense local tissue reactions resulting in severe tissue destruction, septal necrosis or stenosis of the nasal cavity as well as posing the risk of subsequently being ingested or aspirated. This case report details an incidental finding of a button battery in the floor of the nose discovered on routine orthodontic radiographs. An upper standard occlusal and dental panoramic tomography showed a radiopaque, cylindrical, object in the floor of the nose which a subsequent CBCT localized to the floor of the right nasal fossa. The patient required orthodontic extractions and the exposure and bonding of teeth under general anaesthetic. Therefore the battery was removed by the maxillofacial surgery team at the same general anaesthetic. This is a rare case of an incidental finding of a long-standing button battery impaction which was asymptomatic and did not have any detrimental effects. This case highlights the dangers of button battery impaction and the need for prompt referral for removal.

Development of the Malocclusion Impact Questionnaire (MIQ) to measure the oral health-related quality of life of young people with malocclusion: part 1 - qualitative inquiry.

OBJECTIVES: To seek the views of adolescents with malocclusion about how the appearance and arrangement of their teeth affects their everyday life and to incorporate these views into a new Malocclusion Impact Questionnaire (MIQ). METHODS: Semi-structured interviews were undertaken with a purposive sample of 30 young people (10-16 years) referred for orthodontic treatment to two dental teaching hospitals. The interviews were recorded, transcribed and analysed using framework analysis. Several themes and sub themes were identified and these were used to identify items to include in the new measure. RESULTS: Three themes emerged which were: concerns about the appearance of their teeth, effect on social interactions and oral health/function. Participants expressed the view that their teeth did not look normal, causing them embarrassment and a lack of confidence, particularly when they were with their peers or having their photograph taken. Concerns regarding the potential effect of a malocclusion on oral health, in terms of food becoming stuck between crooked teeth, interferences when chewing and increased risk of damaging the teeth were also identified. The themes were used to generate individual items for inclusion in the questionnaire. CONCLUSIONS: Common themes relating to the impact of malocclusion on the lives of young people were identified and generated items for the new MIQ to measure the oral health-related quality of life of young people with malocclusion. Part 2 outlines the further development and testing of the MIQ.