Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features.

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.

Systematic review on the current state of disaster preparation Simulation Exercises (SimEx).

INTRODUCTION: The simulation exercise (SimEx) simulates an emergency in which an elaboration or description of the response is applied. The purpose of these exercises is to validate and improve plans, procedures, and systems for responding to all hazards. The purpose of this study was to review disaster preparation exercises conducted by various national, non-government, and academic institutions. METHODOLOGY: Several databases, including PubMed (Medline), Cumulative Index to Nursing and Allied Health Literature (CINAHL), BioMed Central, and Google Scholar, were used to review the literature. Information was retrieved using Medical Subject Headings (MeSH) and documents were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To assess the quality of the selected articles, the Newcastle-Ottawa Scale (NOS) technique was utilized. RESULTS: A total of 29 papers were selected for final review based on PRISMA guidelines and the NOS quality assessment. Studies have shown that many forms of SimEx commonly used in disaster management including tabletop exercises, functional exercises, and full-scale exercises have their benefits and limitations. There is no doubt that SimEx is an excellent tool for improving disaster planning and response. It is still necessary to give SimEx programs a more rigorous evaluation and to standardize the processes more thoroughly. CONCLUSIONS: Drills and training can be improved for disaster management, which will enable medical professionals to face the challenges of disaster management in the 21st century.

Assessing the coupling between local neural activity and global connectivity fluctuations: Application to human intracranial electroencephalography during a cognitive task.

Cognitive-relevant information is processed by different brain areas that cooperate to eventually produce a response. The relationship between local activity and global brain states during such processes, however, remains for the most part unexplored. To address this question, we designed a simple face-recognition task performed in patients with drug-resistant epilepsy and monitored with intracranial electroencephalography (EEG). Based on our observations, we developed a novel analytical framework (named "local-global" framework) to statistically correlate the brain activity in every recorded gray-matter region with the widespread connectivity fluctuations as proxy to identify concurrent local activations and global brain phenomena that may plausibly reflect a common functional network during cognition. The application of the local-global framework to the data from three subjects showed that similar connectivity fluctuations found across patients were mainly coupled to the local activity of brain areas involved in face information processing. In particular, our findings provide preliminary evidence that the reported global measures might be a novel signature of functional brain activity reorganization when a stimulus is processed in a task context regardless of the specific recorded areas.

The promise of telemedicine in Pakistan: A systematic review.

BACKGROUND: Telemedicine offers the possibility of provision of medical assistance to remote patients, and it has great potential in developing countries like Pakistan. Telemedicine solves logistical barriers, gives support to weak health systems, and helps to establish worldwide networks of healthcare professionals. Because of the high implementation costs, it is not possible yet to adopt telehealth systems for low- and middle-income nations. OBJECTIVE: To present a revision of region-based telemedical services in Pakistan. METHODS: Libraries such as PubMed (Medline), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus (EMBASE), and Google Scholar were used for document search. Newcastle-Ottawa Scale (NOS) was adopted to conduct study quality. Many of the studies (n-8) included in the review were of high quality as assessed through the Newcastle-Ottawa scale. Selected study characteristics were further analyzed based on different parameters such as publication year, sample size, study design, methods, motivation, and outcomes. RESULTS: Search produced 955 articles and 11 items were ultimately selected to conduct the review. These studies were further characterized as region-based telemedicine implementation. Out of 11, eight studies were conducted in the urban region and three studies were conducted in the rural areas of Pakistan. Many studies produced evidence on telehealth interventions by smartphone services such as SMS, apps, and web-based telemedicine. CONCLUSIONS: Telehealth interventions such as mHealth, eHealth, telemedicine, and telepharmacy in Pakistan were introduced starting from the last two decades. For obtaining the full benefits of these technologies, it is necessary that they but certainly need to become an integral part of Pakistan's current health infrastructure.

COVID-19 prevalence and mortality in people with epilepsy: A nation-wide multicenter study.

BACKGROUND: To assess the prevalence, severity, and mortality of COVID-19 in people with epilepsy (PWE) and evaluate seizure control in PWE during and after COVID-19. METHODS: Retrospective, observational, multicenter study conducted in 14 hospitals. Medical records of randomly selected PWE followed at neurology outpatient clinics were reviewed. Proportion of PWE with a positive test for SARS-CoV-2 during 2020 was calculated. Risk factors associated with COVID-19 and its morbimortality were evaluated. RESULTS: 2751 PWE were included, mean age 48.8 years (18-99), 72.4% had focal epilepsy, and 35% were drug-refractory. COVID-19 prevalence in PWE was 5.53%, while in the Spanish population was 4.26%. Proportion of admissions to hospital, ICU, and deaths in PWE were 17.1%, 2%, and 4.61% of COVID-19 cases, while in Spanish population were 10.81%, 0.95%, and 2.57%, respectively. A severe form of COVID-19 occurred in 11.8%; dyslipidemia, institutionalization at long-term care facilities, intellectual disability, and older age were associated risk factors. Older age, hypertension, dyslipidemia, cardiac disease, and institutionalization were associated with mortality from COVID-19. Seizure control was stable in 90.1% of PWE during acute COVID-19, while 8.6% reported an increase in seizure frequency. During post-COVID-19 follow-up, 4.6% reported seizure control worsening. CONCLUSIONS: COVID-19 was moderately prevalent in PWE. One out of 5 patients required medical attention and 4.6% died due to COVID-19. Older age, dyslipidemia, institutionalization, and intellectual disability were significant risk factors associated with severe COVID-19. Seizure control remained stable during COVID-19 and throughout long-term follow-up in most PWE who contracted the infection.

Psychotic symptoms in drug resistant epilepsy patients after cortical stimulation.

PURPOSE: The use of invasive EEG (iEEG) recordings before epilepsy surgery has increased as more complex focal epilepsies are evaluated. Psychotic symptoms (PS) during iEEG have been scarcely reviewed. We aim to report our series of patients with psychotic symptoms (PS) brought about by cortical stimulation (CS) and to identify triggers. METHODS: Retrospective cohort of patients who underwent iEEG and CS. We report patients who developed delusional thinking and/or disorganized behaviour within 24 h after CS. Exclusion criteria were primary psychiatric disorders or absence of CS. RESULTS: We evaluated 32 (SEEG 23; subdural 9) patients with a median age of 38 years, 6 with PS. Patients underwent 2586 stimulations over 1130 contacts. Age at CS was significantly higher in patients with PS. Temporal lobe epilepsy was significantly more often documented in patients with PS (χ2: 3.94; p< 0.05). We found no correlation between stimulation of the limbic system and development of psychosis. Four (66.7 %) patients were stimulated in the non-dominant limbic system and developed psychosis compared to 7 (27 %) who did not [χ2: 3.41; p= 0.06].Epilepsy duration was significantly higher in PS patients (p=0.002). Patients with history of postictal psychosis were twice more likely to experience PS(p=0.04). CONCLUSIONS: PS may arise more frequently in patients with PIP history, older age and longer epilepsy duration. The neurobiology and physiology of psychosis, that may share common mechanisms with epilepsy, is yet to be identified but we hypothesize that it may be triggered by CS due to alteration of brain networks dynamics.

Oral Manifestations of Rett Syndrome-A Systematic Review.

Rett Syndrome is an x linked developmental disorder which becomes apparent in females after 6 to 18 months of age. It leads to severe impairments including loss of speech, loss of hand movements/manual dexterity, characteristic hand movements such as hang wringing and intellectual disability/learning problems. This systematic review was carried out to identify the dental manifestation of Rett syndrome and to shed light on treatment options available for oral health problems associated with Rett syndrome. A systematic literature search was conducted on the PubMed, Scopus, Biomed, Web of Science, Embase, Google Scholars, Cochrane and CINAHL using the following entries: Rett syndrome (n = 3790), Oral health and Rett syndrome (n = 17), dental health of Rett syndrome patients (n = 13), and the MeSH terms listed below: Rett syndrome and Oral Health (n = 17), Rett syndrome and dentistry (n = 29). The final review included 22 search articles. The most common oral findings was bruxism. Masseteric hypertrophy was also reported. Anterior open bite and non-physiological tooth wear was observed. Other oral manifestations of Rett syndrome included mouth breathing, tongue thrusting, digit/thumb sucking, high arch palate. Increased awareness and dental education amongst dentists and assistants regarding the dental manifestations of Rett syndrome and similar neurodevelopmental disorders is required to improve the level of care and empathy they can provide to these differently able patients. Research on dental aspects of Rett is scarce and this remains a neglected topic.

The emerging role of the advanced practice epilepsy nurse: A comparative study between two countries.

AIMS AND OBJECTIVES: The aim of the study was to compare advanced practice in epilepsy nurses in Spain and United Kingdom, identifying differences in the domains of standard advanced practice. BACKGROUND: Europe has recently faced the challenge of providing high-quality care for patients with epilepsy, a disease that generates many health demands. In some countries, such as the United Kingdom, advanced practice nursing is well established and could serve as a guide for implantation in countries where it is still in development, as is the case of Spain. DESIGN: A multicentre cross-sectional descriptive cohort study compared differences in the roles of advanced practice nurses in Spain and the United Kingdom. METHODS: The Advanced Practice Role Delineation Tool and its validated Spanish version were administered using an online questionnaire in a cohort of advanced practice epilepsy nurses in both countries. A convenience sample was recruited between January to December 2019. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. RESULTS: Most United Kingdom nurses in our sample came from community environments, in contrast to Spanish nurses who worked in hospital. All domains analysed in the survey had significantly higher scores in the United Kingdom than in the Spanish cohort, especially in the research and leadership domains. CONCLUSIONS: The advanced practice role in Spain is underdeveloped compared with the United Kingdom. Differences in the settings of advanced roles in epilepsy nurses may be explained by greater community practice in the United Kingdom and differences in organisational and health systems. RELEVANCE TO CLINICAL PRACTICE: Our study showed the need to implement specific policies to develop advance practice nurse roles in Spain to improve the quality of care of patients with epilepsy.

Epilepsy and lockdown: A survey of patients normally attending a Spanish centre.

BACKGROUND: Lockdown due to the SARS-CoV-2 pandemic became a challenge to maintain care for patients with epilepsy; we aimed to find out how the pandemic affected them. METHODS: We sent an online 22-item questionnaire to patients from our outpatient clinic, a reference centre in Spain for drug-resistant epilepsy, inquiring about the effects of lockdown, from March to May 2020. RESULTS: We sent the survey to 627 patients; 312 (58% women) sent a complete response and were included. Of all respondents, 57% took >2 antiseizure medications. One-third of respondents (29%) declared an associated cognitive or motor disability. A minority had confirmed infection with SARS-CoV-2 (1.92%). Seizure frequency remained like usual in 56% of patients, while 31.2% reported an increase. Less than 10% needed emergent assistance. Almost half reported anxiety or depression, and 25% increased behavioural disorders. Mood (F: 5.40; p: 0.002) and sleep disorders (F = 2.67; p: 0.05) were associated with increase in seizure frequency. Patients were able to contact their physicians when needed and were open to a future telematic approach to follow-up visits. CONCLUSIONS: Seizure frequency and severity remained unchanged in most patients during the lockdown. Mood and sleep disorders were common and associated with seizure worsening. Patients were open to telematic care in the future.

Relationship between Socioeconomic Inequalities and Oral Hygiene Indicators in Private and Public Schools in Karachi: An Observational Study.

BACKGROUND: The study investigated the relationship between socioeconomic status and oral hygiene indicators in two schools located in Karachi, Pakistan. Oral hygiene indicators of public and private school children were compared. Private schools cater to children of relatively wealthier families compared to public school, whose attendees are generally children from less affluent backgrounds. The aim of this study was to determine whether socio-economic differences and inequalities have an impact on key oral hygiene indicators. METHODOLOGY: Primary data for this research was collected from community school visits conducted by the community dentistry department of Jinnah Medical and Dental and Medical College from January to September 2019. A convenience sample of the two schools, comprising 300 school students was selected. Data was collected using modified World Health Organization (WHO) oral health care forms. A pre-tested/customized dental hygiene form based on WHO forms was created by the research team. This form was used to measure DMFT/dmft scores and key oral hygiene indicators in the sample. RESULTS: A total sample size of 300 school-children affiliated with public and private schools was selected. The children's age ranged from 2 to 18 years. The mean DMFT scores of private and public-school children were not significantly different (private (1.82) vs. public (1.48)). (p = 0.257). The mean of carious teeth was 1.69 in private school children compared to 1.34 in government school children, whereas the mean values of other key indicators of oral hygiene including plaque deposition (p = 0.001), dental stains (p < 0.001) and bleeding gums/gingivitis (p < 0.001), were statistically significant between public and private school children. CONCLUSION: Oral health inequalities can be reduced with increased awareness and public funding to cater for the oral health needs of children of less affluent families. A dynamic and practical community-oriented program is fundamental for enhancing pediatric oral hygiene status, particularly for children attending government schools.