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Sleep apnea is a common disorder that represents a global public health burden. KCNK3 encodes TASK-1, a K+ channel implicated in the control of breathing, but its link with sleep apnea remains poorly understood. Here we describe a new developmental disorder with associated sleep apnea (developmental delay with sleep apnea, or DDSA) caused by rare de novo gain-of-function mutations in KCNK3. The mutations cluster around the ‘X-gate’, a gating motif that controls channel opening, and produce overactive channels that no longer respond to inhibition by G-protein-coupled receptor pathways. However, despite their defective X-gating, these mutant channels can still be inhibited by a range of known TASK channel inhibitors. These results not only highlight an important new role for TASK-1 K+ channels and their link with sleep apnea but also identify possible therapeutic strategies.

Why a Theatre Laboratory? It includes the programme of a three days’ international symposium from October 4th through 6th 2004. This is the first initiative taken by the Centre for Theatre Laboratory Studies (CTLS), a newly inaugurated centre under Aarhus University in cooperation with Nordisk Teaterlaboratorium. Peripeti include articles on Stanislavski, Meyerhold, Copeau, Decroux, Grotowski, Peter Brook, Théâtre du Soleil, and Odin Teatret and the theatre laboratory praxis of these masters and inventors, including, of course, reflections on their function and effect. In the last article, Eugenio Barba reflects on the creative process of Odin Teatret over the last 40 years. In addition, we also include the curriculum vitae on those participating in the symposium. The occasion of the symposium is to celebrate the 40th anniversary in October 2004 of Nordisk Teaterlaboratorium/Odin Teatret. Congratulations.

A study of the plants, and their associated poisons, in the Poison Garden at The Alnwick Garden was undertaken across a calendar year. By selecting 25 plants in the Poison Garden, we have been able to develop a single chromatographic method for the determination and quantification of 15 plant toxins by liquid chromatography mass spectrometry (LC-MS). Chromatographic separation was achieved on a C18 column (3.5 µm, 100 × 4.6 mm) with a gradient method using water +0.1% formic acid and methanol +0.1% formic acid. The developed method was validated for precision, linearity, limits of detection and quantification and extraction recoveries. The method showed good linearity with a R2 value of >0.995 for all 15 compounds with good precision of 10.7%, 6.7% and 0.3% for the low, medium and high calibration points, respectively. The LC-MS method was used to analyse 25 plant species, as well as their respective parts (i.e., bulb, flower, fruit, leaf, pollen, seed, stem and root), to assess the human risk assessment to children (aged 1 to

The study aimed at widening the clinical and genetic spectrum of ASXL3-related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3-related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3-related syndrome, we define its natural history and clinical evolution occurring with age. We report familial ASXL3 pathogenic variants, characterize the phenotype in mildly affected individuals and discuss nonpenetrance. We also discuss the role of missense variants in ASXL3. We delineate a variable but consistent phenotype. The most characteristic features are neurodevelopmental delay with consistently limited speech, significant neuro-behavioral issues, hypotonia, and feeding difficulties. Distinctive features include downslanting palpebral fissures, hypertelorism, tubular nose with a prominent nasal bridge, and low-hanging columella. The presented data will inform clinical management of individuals with ASXL3-related syndrome and improve interpretation of new ASXL3 sequence variants.

– This study investigated how Nigerian newspapers contributed to sensitizing and sustaining public attention on the issue of the schoolgirls that were abducted by the Boko Haram group in Chibok, northeastern Nigeria. The study analyzed the direction/slant, frequency, and prominence of news stories, feature articles, editorials, special reports, interpretative articles, and news analysis on the abduction as published in three major Nigerian newspapers. Using the content analytical technique, the study found that there was no day in the period under investigation that the issue of the abducted Chibok girls did not get attention in the press. The study also found that the press discharged its corporate social responsibility by setting and sustaining public consciousness on the injustice and inhumanity of the abduction. Furthermore, a connection was established between the unrelenting crusade mounted by non-governmental organizations, especially the #BringBackOurGirls movement, for the release of the abducted girls, sustained public interest provided by the Press, and the eventual government action that culminated in the release of 164 out of the 276 girls initially abducted. This study, therefore, recommends continued publicity by the media in its role as a social crusader to ensure that the remaining Chibok and other abductees are rescued from their Boko Haram abductors.RESUMO – Este estudo investigou como os jornais nigerianos contribuíram para sensibilizar e manter a atenção do público sobre a questão das estudantes que foram sequestradas pelo grupo Boko Haram em Chibok, no nordeste da Nigéria. O estudo analisou o direcionamento/ponto de vista, a frequência e proeminência das notícias, artigos de destaque, editoriais, reportagens especiais, artigos interpretativos e análises de notícias sobre o sequestro nas publicações dos três principais jornais nigerianos. Usando técnica analítica de conteúdo, o estudo identificou que, no período investigado, não houve um dia em que a pauta do sequestro não tenha recebido atenção da imprensa. O estudo descobriu também que a imprensa cumpriu sua responsabilidade social corporativa ao estabelecer e manter a consciência pública sobre a injustiça e desumanidade do sequestro. Além disso, uma conexão foi estabelecida entre a cruzada incessante montada por organizações não governamentais, especialmente o movimento #BringBackOurGirls, pela libertação das meninas, e sustentou o interesse público proporcionado pela imprensa e a eventual ação governamental que culminou com a libertação de 164 das 276 garotas inicialmente sequestradas. Portanto, este estudo recomenda a continuidade da visibilidade proporcionada pela mídia no seu papel de cruzada social para assegurar que Chiboks e outros raptados sejam resgatados dos seus sequestradores do Boko Haram.RESUMEN – En este estudio se investiga cómo los periódicos nigerianos contribuyeron a sensibilizar y mantener la atención pública sobre la cuestión de las niñas secuestradas por el grupo Boko Haram en Chibok, al noreste de Nigeria. El estudio analizó la dirección/orientación, frecuencia y prominencia de las noticias, artículos de fondo, editoriales, informes especiales, artículos interpretativos y análisis periodísticos sobre el secuestro, publicados en tres importantes periódicos nigerianos. Mediante el uso de la técnica del análisis de contenido, el estudio llegó a la conclusión de que no había ningún día en el período investigado en que el asunto de las niñas Chibok secuestradas no recibiera atención en la prensa. También se encontró que la prensa cumplió con su responsabilidad social corporativa al establecer y mantener la conciencia pública sobre la injusticia y la falta de humanidad del secuestro. Además, se estableció una conexión entre la implacable cruzada montada por organizaciones no gubernamentales, especialmente el movimiento #BringBackOurGirls, por la liberación de las niñas secuestradas, el interés público sostenido proporcionado por la prensa, y la eventual acción gubernamental que culminó en la liberación de 164 de las 276 niñas inicialmente secuestradas. Por lo tanto, en este estudio se recomienda que los medios de comunicación continúen otorgando publicidad, en su rol público de luchadores sociales, para garantizar que los restantes Chibok y otros secuestrados sean rescatados de sus secuestradores de Boko Haram.

Background The appendix has a unique place in surgical history. Although the first ever appendicectomy involved a fistula to the skin, fistulae involving the appendix remain uncommon and can lead to unique surgical considerations. Methods A systematic review of the literature was performed for case reports of appendiceal fistulae. We excluded cases in which the patient had a history of appendicectomy. Cases were categorized by site and aetiology, with information regarding relative frequency and demographics obtained. Results A total of 301 case reports of fistula involving the appendix were found. The most common sites of these fistulae were to the bladder (148 cases), skin (40 cases), vasculature (19 cases), umbilicus (16 cases) and to the gastrointestinal tract. The most common aetiology in sub-analysis was appendicitis alone (150 cases), with less common causes including appendiceal adenocarcinoma (32 cases) and congenital abnormalities (18 cases). There were significantly more appendiceal fistulae in males than in females, with a ratio of 1.7:1. In patients with appendiceal adenocarcinoma as a cause for fistula, there were significantly more females than males with a ratio of 2.3:1. Conclusion In conducting a systematic review of case reports of fistulae involving the appendix, we identified 301 unique case reports, with a range of different sites and aetiologies.

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Social isolation imposed by the COVID-19 pandemic negatively impacted people’s lifestyles and daily activities. In this work we compared pre- and post-pandemic clinical outcomes in people with Parkinson’s disease, to assess differences according to the type of behaviour and exercise habits adopted by participants. After two months of COVID-19 lockdown, we assessed: changes in exercise behaviour; motor and non-motor aspects of daily life experiences (MDS-UPDRS I & II); activities of daily living (The Schwab & England scale); quality of life (Parkinson Disease Questionnaire); sleep (Parkinson Disease Sleep Scale); falls; and Clinical Global Impression Change. Twenty-seven individuals aged between 57 and 92 years old participated; from these, ten individuals (37%) completely interrupted physical activities, while seventeen (63%) maintained some level of active lifestyle. Regardless of whether they remained active or not, all participants perceived a significant worsening of their clinical condition, reporting an increase in difficulties completing daily activities or chores (37%) and worsening of their health condition (51.8%). The quantifiable influence of exercise habits was borderline for the group who kept active. The active group seem to have a better self-perception of their health condition, although it was not enough to show a clear benefit. People with Parkinson’s disease should be informed that being physically active may not be enough and more structured exercise could be needed. info:eu-repo/semantics/publishedVersion

Adrenal insufficiency (AI) is an often-unrecognised endocrine disorder, which can lead to adrenal crisis and death if not identified and treated. Omission of steroids in patients with AI, particularly during physiological stress such as an intercurrent illness or surgery, can also lead to an adrenal crisis. The National Reporting and Learning System (NRLS) identified 78 incidents including two deaths and six incidents of severe harm to patients in a recent 4-year period. This guidance will go through causes of adrenal insufficiency, groups at risk of an adrenal crisis, emergency management and management for surgical procedures. A new NHS Steroid Emergency Card has been developed to be carried by patients at risk of adrenal crisis. We hope the new emergency card and this guidance will increase awareness of the need to start steroids promptly in patients at risk of an adrenal crisis, particularly those presenting in the emergency department or to acute medicine teams and those undergoing surgery or invasive procedures.

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data.

IntroductionThe purpose of VIKING II is to create an observational cohort of volunteers with ancestry from the Northern Isles of Scotland, primarily for identifying genetic variants influencing disease. The new online protocol is separate to, but follows on from, earlier genetic epidemiological clinic-based studies in the isolated populations of Orkney and Shetland. These populations are favourable for the study of rarer genetic variants due to genetic drift, the large number of relatives, and availability of pedigree information.Methods and AnalysisOnline methods are being used to recruit ∼4,000 people who have Northern Isles ancestry, living anywhere in the world. The option for participants to have actionable genetic results returned is offered. Broad consent will be taken electronically. Data will be collected at baseline through an online questionnaire and longitudinally through linkage to NHS data in the electronic health record. The questionnaire collects a variety of phenotypes including personal and family health. DNA will be extracted from saliva samples then genome-wide genotyped and exome sequenced. VIKING II aims to capitalise on the special features of the Northern Isles populations to create a research cohort that will facilitate the analysis of genetic variants associated with a broad range of traits and disease endpoints.Ethics and DisseminationThe South East Scotland Research Ethics Committee gave the study a favourable opinion. VIKING II is sponsored by the University of Edinburgh and NHS Lothian. Summary research findings will be disseminated to participants and funding bodies, presented at conferences and reported in peer-reviewed publications.Article SummaryStrengths and limitations of this studyDetailed data and biological sample collection of research volunteers with unique ancestry.Consent for access to routinely collected clinical EHR data and for future re-contact, providing a longitudinal component.Optional consent for return of actionable genetic results.4,000 participants is a relatively small number for certain types of genetic analyses, so the cohort is underpowered on its own, in some study designs.Resources to maintain the cohort, and to store data and DNA samples, are significant, with sustainability dependent on infrastructure support and continued funding.

Background Dual-task training is an emerging field used for people with Parkinson disease (PD) to improve their physical and cognitive well-being, but the patients’ acceptability, safety, and adherence to such training in online settings are unknown. Objective This study aims to evaluate the acceptability of a dual-task cognitive and motor online training program for people with PD as a group online community program. Methods People with PD were invited to participate in an online program (PD3 Move) consisting of physical and vocal exercises in response to different cognitive challenges displayed as dynamic backgrounds on Zoom. The program ran twice per week for 16 weeks. Patient acceptability was assessed at 4 months by monitoring attendance rates and feedback from an exit questionnaire emailed to all participants assessing satisfaction, perceived benefit, safety, and willingness to continue and recommend to others. Results The online program was delivered to 15 participants (n=9, 60%, females) with a diagnosis of PD, a mean age of 69.4 (SD 9.3) years, and Hoehn and Yahr (H&Y) stages I-IV. The attendance rate was high, with participants coming to more than 13 (81%) of the sessions. Participants were very satisfied (n=8, 53%) or satisfied (n=7, 47%) with the program. Participants reported that what they most liked were the new cognitive physical challenges. The 3 main facilitators to participating were perceiving the benefits, instructor’s flexibility and engagement, and the social interaction moments with others. The 3 main difficulties were dealing with motor fluctuations (n=3, 20%), difficulties in using technology (n=2, 13%), and difficulty hearing instructions due to hearing loss (n=2, 13%). Patients had favorable perceived benefits of the program, with 14 (93%) considering it very useful for the current management of health and 1 (7%) moderately useful. No adverse events were reported, and all participants said that they were willing to continue the program and recommend it to others. Conclusions Our findings suggest that the online cognitive and motor program was well received, safe, and perceived to be of benefit to this group of medically stable people with PD in H&Y stages I-IV. Access to specialized care and enhancement of long-term adherence to regular exercise can be achieved with online community group programs.

Any transition of patient care is a high-risk time for communication error. This paper explores whether the presence of a pharmacist as part of an interprofessional group provides additional benefit and safety in transitions of care.Six pharmacy interns and newly qualified pharmacists joined participants from seven other health professional training programmes to take part in an interprofessional education activity. Participants were assigned to 24 mixed-professional groups. Each group was required to craft a discharge summary for the same simulated patient. Groups without a pharmacist were given additional written documentation, including medication reconciliation, discharge prescription and discharge recommendations. The 24 discharge summaries were assessed for any medication-related information, both positive and negative. Groups with a pharmacist (6) were compared with groups who did not have a pharmacist (18) for completeness and accuracy of medication management.An in-person pharmacist provided more thorough, comprehensive, accessible and accurate information for the community team (p=0.003). Although there was no difference in the absolute number of medication errors between the groups (p=0.057), the groups with a pharmacist showed a significant reduction in the severity of the errors (p=0.009). This result happened despite the groups without a pharmacist being provided with all the required medication information for safe transition of care.These findings support the case for greater involvement from a pharmacist in a patient's healthcare team, particularly for any transition of care. Healthcare teams that include a pharmacist are more likely to exceed minimum safety expectations and make less severe errors.

The use of vermicompost water extracts (teas) in horticulture to increase plant growth and yield and suppress pests and diseases, is well documented. However, its utilization and effects in hydropo...

Contains fulltext : 209024.pdf (Publisher’s version ) (Open Access) BACKGROUND: Persons with Parkinson's disease (PD) benefit from continuous exercise through participation in community-based exercise programs. However, community programs often lack PD-specific knowledge needed to provide safe and adequately dosed exercise. OBJECTIVE: To evaluate the acceptability and safety of a PD-specific boxing program in the community. METHODS: We developed specific educational resources to facilitate the boxing instructors. We also organized an educational and practical workshop for patients (n = 26) and instructors (n = 10), and assessed: (a) participants' satisfaction; (b) instructors' appreciation of the educational resources; and (c) numbers of patients interested in participating in the boxing program. After 18 months, patients and instructors completed a questionnaire evaluating: (a) participants' satisfaction; (b) adverse events; (c) facilitators and barriers; and (d) proportion of participants at follow-up. RESULTS: Twenty-six persons with PD (62% men) and 10 boxing instructors participated in the workshop. 81% of patients and 80% of instructors were very satisfied. Instructors found the educational materials "very helpful" (60%) or "helpful" (40%). Patients expressed a clear interest (54%) or possible interest (46%) in the program. We initiated classes with 10 participants. At 18-months follow-up, the program consisted of four boxing sessions/week, led by three instructors, with 40 participants. Seventeen patients responded to the questionnaire at follow-up. Participants were "very satisfied" (53%), "satisfied" (35%) and neither satisfied nor unsatisfied (12%) with the program. Adverse effects were mild (e.g., muscle aches). Transportation and physical disability were the main barriers for participation. CONCLUSIONS: The boxing program was well-received, with increasing numbers of participants at 18 months. The educational resources can support boxing instructors participating in current and future boxing classes being delivered in the community.