Retinal Architecture in ​\u3cem\u3eRGS9-\u3c/em\u3e and ​\u3cem\u3eR9AP\u3c/em\u3e-Associated Retinal Dysfunction (Bradyopsia)

Purpose To characterize photoreceptor structure and mosaic integrity in subjects with RGS9- and R9AP-associated retinal dysfunction (bradyopsia) and compare to previous observations in other cone dysfunction disorders such as oligocone trichromacy. Design Observational case series. Methods setting: Moorfields Eye Hospital (United Kingdom) and Medical College Wisconsin (USA). study population: Six eyes of 3 subjects with disease-causing variants in RGS9 or R9AP. main outcome measures: Detailed retinal imaging using spectral-domain optical coherence tomography and confocal adaptive-optics scanning light ophthalmoscopy. Results Cone density at 100 μm from foveal center ranged from 123 132 cones/mm2to 140 013 cones/mm2. Cone density ranged from 30 573 to 34 876 cones/mm2 by 600 μm from center and from 15 987 to 16,253 cones/mm2 by 1400 μm from center, in keeping with data from normal subjects. Adaptive-optics imaging identified a small, focal hyporeflective lesion at the foveal center in both eyes of the subject with RGS9-associated disease, corresponding to a discrete outer retinal defect also observed on spectral-domain optical coherence tomography; however, the photoreceptor mosaic remained intact at all other observed eccentricities. Conclusions Bradyopsia and oligocone trichromacy share common clinical symptoms and cannot be discerned on standard clinical findings alone. Adaptive-optics imaging previously demonstrated a sparse mosaic of normal wave-guiding cones remaining at the fovea, with no visible structure outside the central fovea in oligocone trichromacy. In contrast, the subjects presented in this study with molecularly confirmed bradyopsia had a relatively intact and structurally normal photoreceptor mosaic, allowing the distinction between these disorders based on the cellular phenotype and suggesting different pathomechanisms

Mental health first aid training of the public in a rural area: a cluster randomized trial [ISRCTN53887541]

BACKGROUND: A Mental Health First Aid course has been developed which trains members of the public in how to give initial help in mental health crisis situations and to support people developing mental health problems. This course has previously been evaluated in a randomized controlled trial in a workplace setting and found to produce a number of positive effects. However, this was an efficacy trial under relatively ideal conditions. Here we report the results of an effectiveness trial in which the course is given under more typical conditions. METHODS: The course was taught to members of the public in a large rural area in Australia by staff of an area health service. The 16 Local Government Areas that made up the area were grouped into pairs matched for size, geography and socio-economic level. One of each Local Government Area pair was randomised to receive immediate training while one served as a wait-list control. There were 753 participants in the trial: 416 in the 8 trained areas and 337 in the 8 control areas. Outcomes measured before the course started and 4 months after it ended were knowledge of mental disorders, confidence in providing help, actual help provided, and social distance towards people with mental disorders. The data were analysed taking account of the clustered design and using an intention-to-treat approach. RESULTS: Training was found to produce significantly greater recognition of the disorders, increased agreement with health professionals about which interventions are likely to be helpful, decreased social distance, increased confidence in providing help to others, and an increase in help actually provided. There was no change in the number of people with mental health problems that trainees had contact with nor in the percentage advising someone to seek professional help. CONCLUSIONS: Mental Health First Aid training produces positive changes in knowledge, attitudes and behaviour when the course is given to members of the public by instructors from the local health service

INDIGO - INtegrated Data Warehouse of MIcrobial GenOmes with Examples from the Red Sea Extremophiles.

Background: The next generation sequencing technologies substantially increased the throughput of microbial genome sequencing. To functionally annotate newly sequenced microbial genomes, a variety of experimental and computational methods are used. Integration of information from different sources is a powerful approach to enhance such annotation. Functional analysis of microbial genomes, necessary for downstream experiments, crucially depends on this annotation but it is hampered by the current lack of suitable information integration and exploration systems for microbial genomes. Results: We developed a data warehouse system (INDIGO) that enables the integration of annotations for exploration and analysis of newly sequenced microbial genomes. INDIGO offers an opportunity to construct complex queries and combine annotations from multiple sources starting from genomic sequence to protein domain, gene ontology and pathway levels. This data warehouse is aimed at being populated with information from genomes of pure cultures and uncultured single cells of Red Sea bacteria and Archaea. Currently, INDIGO contains information from Salinisphaera shabanensis, Haloplasma contractile, and Halorhabdus tiamatea - extremophiles isolated from deep-sea anoxic brine lakes of the Red Sea. We provide examples of utilizing the system to gain new insights into specific aspects on the unique lifestyle and adaptations of these organisms to extreme environments. Conclusions: We developed a data warehouse system, INDIGO, which enables comprehensive integration of information from various resources to be used for annotation, exploration and analysis of microbial genomes. It will be regularly updated and extended with new genomes. It is aimed to serve as a resource dedicated to the Red Sea microbes. In addition, through INDIGO, we provide our Automatic Annotation of Microbial Genomes (AAMG) pipeline. The INDIGO web server is freely available at http://www.cbrc.kaust.edu.sa/indigo.IA and AAK were supported from the KAUST CBRC Base Fund of VBB. WBa and VBB were supported from the KAUST Base Funds of VBB. US was supported by the KAUST Base Fund of US. This study was partly supported by the Saudi Economic and Development Company (SEDCO) Research Excellence award to US and VBB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Mental health first aid training in a workplace setting: A randomized controlled trial [ISRCTN13249129]

BACKGROUND: The Mental Health First Aid training course was favorably evaluated in an uncontrolled trial in 2002 showing improvements in participants' mental health literacy, including knowledge, stigmatizing attitudes, confidence and help provided to others. This article reports the first randomized controlled trial of this course. METHODS: Data are reported on 301 participants randomized to either participate immediately in a course or to be wait-listed for 5 months before undertaking the training. The participants were employees in two large government departments in Canberra, Australia, where the courses were conducted during participants' work time. Data were analyzed according to an intention-to-treat approach. RESULTS: The trial found a number of benefits from this training course, including greater confidence in providing help to others, greater likelihood of advising people to seek professional help, improved concordance with health professionals about treatments, and decreased stigmatizing attitudes. An additional unexpected but exciting finding was an improvement in the mental health of the participants themselves. CONCLUSIONS: The Mental Health First Aid training has shown itself to be not only an effective way to improve participants' mental health literacy but also to improve their own mental health. It is a course that has high applicability across the community

Development of mental health first aid guidelines for suicidal ideation and behaviour: A Delphi study

<p>Abstract</p> <p>Background</p> <p>Suicide is a statistically rare event, but devastating to those left behind and one of the worst possible outcomes associated with mental illness. Although a friend, family member or co-worker may be the first person to notice that a person is highly distressed, few have the knowledge and skills required to assist. Simple guidelines may help such a person to encourage a suicidal individual to seek professional help or decide against suicide.</p> <p>Methods</p> <p>This research was conducted using the Delphi methodology, a method of reaching consensus in a panel of experts. Experts recruited to the panels included 22 professionals, 10 people who had been suicidal in the past and 6 carers of people who had been suicidal in the past. Statements about how to assist someone who is thinking about suicide were sourced through a systematic search of both professional and lay literature. The guidelines were written using the items most consistently endorsed by all three panels.</p> <p>Results</p> <p>Of 114 statements presented to the panels, 30 were accepted. These statements were used to develop the guidelines appended to this paper.</p> <p>Conclusion</p> <p>There are a number of actions which are considered to be useful for members of the public when they encounter someone who is experiencing suicidal thoughts or engaging in suicidal behaviour. These guidelines will be useful in revision of curricula of mental health first aid and suicide intervention training programs. They can also be used by members of the public who want immediate information about how to assist a suicidal person.</p

Topological Surface States Protected From Backscattering by Chiral Spin Texture

Topological insulators are a new class of insulators in which a bulk gap for electronic excitations is generated by strong spin orbit coupling. These novel materials are distinguished from ordinary insulators by the presence of gapless metallic boundary states, akin to the chiral edge modes in quantum Hall systems, but with unconventional spin textures. Recently, experiments and theoretical efforts have provided strong evidence for both two- and three-dimensional topological insulators and their novel edge and surface states in semiconductor quantum well structures and several Bi-based compounds. A key characteristic of these spin-textured boundary states is their insensitivity to spin-independent scattering, which protects them from backscattering and localization. These chiral states are potentially useful for spin-based electronics, in which long spin coherence is critical, and also for quantum computing applications, where topological protection can enable fault-tolerant information processing. Here we use a scanning tunneling microscope (STM) to visualize the gapless surface states of the three-dimensional topological insulator BiSb and to examine their scattering behavior from disorder caused by random alloying in this compound. Combining STM and angle-resolved photoemission spectroscopy, we show that despite strong atomic scale disorder, backscattering between states of opposite momentum and opposite spin is absent. Our observation of spin-selective scattering demonstrates that the chiral nature of these states protects the spin of the carriers; they therefore have the potential to be used for coherent spin transport in spintronic devices.Comment: to be appear in Nature on August 9, 200

Experiences in applying skills learned in a mental health first aid training course: a qualitative study of participants' stories

BACKGROUND: Given the high prevalence of mental disorders and the comparatively low rate of professional help-seeking, it is useful for members of the public to have some skills in how to assist people developing mental disorders. A Mental Health First Aid course has been developed to provide these skills. Two randomized controlled trials of this course have shown positive effects on participants' knowledge, attitudes and behavior. However, these trials have provided limited data on participants' subsequent experiences in providing first aid. To remedy this, a study was carried out gathering stories from participants in one of the trials, 19–21 months post-training. METHODS: Former course participants were contacted and sent a questionnaire either by post or via the internet. Responses were received from 94 out of the 131 trainees who were contacted. The questionnaire asked about whether the participant had experienced a post-training situation where someone appeared to have a mental health problem and, if so, asked questions about that experience. RESULTS: Post-training experiences were reported by 78% of respondents. Five key points emerged from the qualitative data: (1) the majority of respondents had had some direct experience of a situation where mental health issues were salient and the course enabled them to take steps that led to better effects than otherwise might have been the case; (2) positive effects were experienced in terms of increased empathy and confidence, as well as being better able to handle crises; (3) the positive effects were experienced by a wide range of people with varied expectations and needs; (4) there was no evidence of people over-reaching themselves because of over-confidence and (5) those who attended were able to identify quite specific benefits and many thought the course not only very useful, but were keen to see it repeated and extended. CONCLUSION: The qualitative data confirm that most members of the public who receive Mental Health First Aid training subsequently provide support to people with mental health problems and that this support generally has positive effects

Decompressive Hemicraniectomy: Predictors and Functional Outcome In Patients With Ischemic Stroke

BACKGROUND Patients presenting with large ischemic strokes may develop uncontrollable, progressive brain edema that risks compression of brain parenchyma and cerebral herniation.1 Edema that does not respond to medical treatment necessitates decompressive hemicraniectomy (DH) as a life-saving procedure. The functional outcome of patients is uncertain and the patient’s family is presented with the difficult decision of intervention with DH. While the functional outcome of patients is not worsened by DH,2 neurological deficit is likely as a result of initial large-territory ischemia. The correlation of specific clinical variables preceding DH to patient outcome helps inform clinicians and families about prognosis.3 This study identifies an array of clinical variables in patients who underwent DH for ischemic stroke in order to investigate potential predictors of functional outcome. METHOD A total of 1,624 subjects that underwent any type of craniectomy from 2006 to 2014 were retrospectively screened via electronic medical record. The specific selection criterion was DH secondary to ischemic stroke involving the middle cerebral artery (MCA), internal carotid artery (ICA), or both. Subjects were excluded if they underwent craniectomy for any reason other than DH for ischemic stroke; or if the MCA or ICA were not implicated. The clinical variables that were collected may be divided into pre-DH and post-DH. The pre-DH variables involve patient demographics and past medical history, in addition to clinical variables during the period of presentation and clinical management leading up to DH. The post-DH variables describe the in-patient recovery period and discharge status. The primary outcome was functional status assessed by the Modified Rankin Scale (MRS) score at 90 days post-DH. The MRS ranges from 0 (no symptoms) to 6 (death) with intermediate values (1-5) representing increasing functional and cognitive disability

A broad distribution of the alternative oxidase in microsporidian parasites

Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome