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Contains fulltext : 282534.pdf (Publisher’s version ) (Open Access), BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) has a high degree of sensitivity and specificity for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) and this has led to its being included in revised European CJD Surveillance Network diagnostic criteria for sCJD. As CSF RT-QuIC becomes more widely established, it is crucial that the analytical performance of individual laboratories is consistent. The aim of this ring-trial was to ascertain the degree of concordance between European countries undertaking CSF RT-QuIC. METHODS: Ten identical CSF samples, seven from probable or neuropathologically confirmed sCJD and three from non-CJD cases, were sent to 13 laboratories from 11 countries for RT-QuIC analysis. A range of instrumentation and different recombinant prion protein substrates were used. Each laboratory analysed the CSF samples blinded to the diagnosis and reported the results as positive or negative. RESULTS: All 13 laboratories correctly identified five of the seven sCJD cases and the remaining two sCJD cases were identified by 92% of laboratories. Of the two sCJD cases that were not identified by all laboratories, one had a disease duration >26 months with a negative 14-3-3, whilst the remaining case had a 4-month disease duration and a positive 14-3-3. A single false positive CSF RT-QuIC result was observed in this study. CONCLUSIONS: This study shows that CSF RT-QuIC demonstrates an excellent concordance between centres, even when using a variety of instrumentation, recombinant prion protein substrates and CSF volumes. The adoption of CSF RT-QuIC by all CJD surveillance centres is recommended.

Background: The efficacy of psychoeducation as an add-on treatment to pharmacotherapy is well documented in treating symptoms and in relapse prevention for persons with bipolar disorder in western countries. Yet, no studies on psychosocial interventions for persons with bipolar disorder have been conducted in a low-income country in Africa. Aim: To develop a bipolar group psychoeducation program contextualized to the Rwandese setting, and determine its effect on symptom severity, medical adherence, and internalized stigma. Methods: A culturally adapted guide manual was developed by local mental health professionals, including nurses, psychologists, and medical doctors. In-depth interviews with participants were held prior to and will be held following the intervention to address the cultural aspect of living with bipolar disease and the impact of the program. A two-armed randomized controlled trial has been set up at the tertiary mental health hospitals in Rwanda, with an intervention and a waiting list arm. A sample size of at least 50 in each arm was calculated as a requirement. The study’s primary outcome measure will be the difference in relapse rate measured on the Young Mania Rating Scale and Hamilton Depression Scale-17. Differences in mean change on scales for medical adherence and internalized stigma will be secondary outcomes. Data will be analyzed according to the intention-to-treat principle. Participants will be assessed subsequently at baseline, at the end of the intervention period, and three months and 12 months post-intervention. Discussion: This study will be one of the first intervention trials on bipolar disorder in a low-income country. If proven successful in reducing morbidity and increasing the quality of life in persons with bipolar disorder, it is anticipated that the psychoeducation program can be implemented at the district and community level and act as inspiration for other low-resource settings. Trial registration: ClinicalTrials.go

Background: The treatment gap for bipolar disorder is aggravated by economic inequality. Around half of the world's population live in a low-or lower-middle-income country, where research on treatment is scarce. Hence, this review aims to determine the number and types of intervention studies conducted on adults with bipolar disorder in low-income and lower-middle-income countries and analyze the effect of these interventions on symptom severity, medical adherence, and quality of life. Methods: A systematic review was conducted in June and November 2021 using eight databases. Controlled intervention trials on adults with bipolar disorder on data from low-income and lower-middle-income countries at time of publication were included. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or The Risk Of Bias In Non-randomized Studies of Interventions assessment tool. Results: Twenty-one studies met the inclusion criteria. These were divided into four subtypes based on the intervention; pharmacotherapy (=12), psychosocial (=7), electroconvulsive therapy (=1), and traditional medicine (=1). Three studies were from low-income countries. A high risk of bias characterized the studies; only four studies reported the procedures used for randomization. Most studies, however, identified a beneficial effect on symptom severity, and in addition, medical adherence could be improved with psychosocial interventions. Limitations: Heterogeneity across studies prevented any meaningful pooling of data to meta-analyses. Conclusion: Data for treatment interventions contextualized to the local setting for bipolar disorder remains sparse, particularly from low-resource settings. Further studies are urgently needed to target the treatment gap for bipolar disorder. Trial registration: PROSPERO: CRD42020170953.

Knowledge about psychological distress in older cardiac arrest (CA) survivors is sparse, and the lack of comparisons with general populations make it difficult to draw any strong conclusions about prevalence and potential changes caused by CA. Our aim was to compare psychological distress between older CA survivors and a general population. This study included survivors 65–80 years old and an age‐ and sex‐matched general population. Data on survivors was collected from the Swedish Register of Cardiopulmonary Resuscitation. The Hospital Anxiety and Depression Scale was used to measure psychological distress. Data were analyzed with non-parametric statistics. The final sample included 1,027 CA survivors and 1018 persons from the general population. In both groups, the mean age was 72 years (SD = 4) and 28% were women. The prevalence of anxiety was 9.9% for survivors and 9.5% for the general population, while the corresponding prevalence for depression was 11.3% and 11.5% respectively. Using the cut‐off scores, no significant differences between the groups were detected. However, CA survivors reported significantly lower symptom levels using the subscale scores (ΔMdn = 1, p < 0.001). In conclusion, the CA survivors did not report higher symptom levels of anxiety and depression than the general population. However, since psychological distress is related to poor quality‐of‐life and recovery, screening for psychological distress remains important. © 2021 by the authors.

The adenosine A1 receptor (A1R) is a promising therapeutic target for non-opioid analgesic agents to treat neuropathic pain1,2. However, development of analgesic orthosteric A1R agonists has failed because of a lack of sufficient on-target selectivity as well as off-tissue adverse effects3. Here we show that [2-amino-4-(3,5-bis(trifluoromethyl)phenyl)thiophen-3-yl)(4-chlorophenyl)methanone] (MIPS521), a positive allosteric modulator of the A1R, exhibits analgesic efficacy in rats in vivo through modulation of the increased levels of endogenous adenosine that occur in the spinal cord of rats with neuropathic pain. We also report the structure of the A1R co-bound to adenosine, MIPS521 and a Gi2 heterotrimer, revealing an extrahelical lipid-detergent-facing allosteric binding pocket that involves transmembrane helixes 1, 6 and 7. Molecular dynamics simulations and ligand kinetic binding experiments support a mechanism whereby MIPS521 stabilizes the adenosine-receptor-G protein complex. This study provides proof of concept for structure-based allosteric drug design of non-opioid analgesic agents that are specific to disease contexts.

Background: The values and attitudes of healthcare professionals influence their handling of ‘do-not-attempt-resuscitation’ (DNAR) orders. The aim of this study was a) to describe attitudes, perceptions and practices among Swedish physicians and nurses towards discussing cardiopulmonary resuscitation and DNAR orders with patients and their relatives, and b) to investigate if the physicians and nurses were familiar with the national ethical guidelines for cardiopulmonary resuscitation. Methods: This was a retrospective observational study based on a questionnaire and was conducted at 19 wards in two regional hospitals and one county hospital. Results: 210 physicians and 312 nurses (n = 522) responded to the questionnaire. Every third (35%) professional had read the guidelines with a lower proportion of physicians (29%) compared to nurses (38%). Around 40% of patients had the opportunity or ability to participate in the DNAR discussion. The DNAR decision was discussed with 38% of patients and the prognosis with 46%. Of the patients who were considered to have the ability to participate in the discussion, 79% did so. The majority (81%) of physicians and nurses believed that patients should always be asked about their preferences before a DNAR decision was made. Conclusions: Swedish healthcare professionals take a patient’s autonomy into account regarding DNAR decisions. Nevertheless, as 50% of patients were considered unable to participate in the DNAR discussion, questions remain about the timing of patient participation and whether more discussions could have been conducted earlier. Given the uncertainty about timing, the majority of patients deemed competent participated in DNAR discussions. © 2021, The Author(s).

Polymetallic sulfide (PMS) deposits produced at hydrothermal vents in the deep sea are of potential interest to miners. Hydrothermally active sulfide ecosystems are valued for the extraordinary chemosynthetic communities that they support. Many countries, including Canada, Portugal, and the United States, protect vent ecosystems in their Exclusive Economic Zones. When hydrothermal activity ceases temporarily (dormancy) or permanently (extinction), the habitat and associated ecosystem change dramatically. Until recently, so-called “inactive sulfide” habitats, either dormant or extinct, received little attention from biologists. However, the need for environmental management of deep-sea mining places new imperatives for building scientific understanding of the structure and function of inactive PMS deposits. This paper calls for actions of the scientific community and the emergent seabed mining industry to i) undertake fundamental ecological descriptions and study of ecosystem functions and services associated with hydrothermally inactive PMS deposits, ii) evaluate potential environmental risks to ecosystems of inactive PMS deposits through research, and iii) identify environmental management needs that may enable mining of inactive PMS deposits. Mining of some extinct PMS deposits may have reduced environmental risk compared to other seabed mining activities, but this must be validated through scientific research on a case-by-case basis.