Search

Introduction Psychiatric inpatient care (PIC) is often characterised by high pressure and thresholds for admission, brief periods of care and limited time for caring activities. Dissociative identity disorder (DID) is a contested diagnosis, and persons with DID are at risk of not receiving adequate support when cared for in PIC. Because the limited literature addressing the topic includes no overview on how persons with DID are cared for in psychiatric inpatient settings, the aim of this scoping review is to map the area of knowledge on PIC for persons experiencing DID. This scoping review will provide an overview with the possibility to elucidate gaps in the evidence base and needs for future research on PIC for persons experiencing DID.Methods and analysis This scoping review will follow Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews and steps 1–5 described in the established method for scoping reviews: identifying research question, identifying relevant studies, study selection, charting the data and collating, summarising and reporting results.Ethics approval Not applicable.Dissemination This scoping review will be submitted for publication in an international, peer-reviewed journal.

Abstract The CRISPR/Cas9 system offers enormous versatility for functional genomics but many applications have proven to be challenging in primary human cells compared to cell lines or mouse cells. Here, to establish a paradigm for multiplexed gene editing in primary human cord blood-derived hematopoietic stem and progenitor cells (HSPCs), we used co-delivery of lentiviral sgRNA vectors expressing either Enhanced Green Fluorescent Protein (EGFP) or Kusabira Orange (KuO), together with Cas9 mRNA, to simultaneously edit two genetic loci. The fluorescent markers allow for tracking of either single- or double-edited cells, and we could achieve robust double knockout of the cell surface molecules CD45 and CD44 with an efficiency of ~ 70%. As a functional proof of concept, we demonstrate that this system can be used to model gene dependencies for cell survival, by simultaneously targeting the cohesin genes STAG1 and STAG2. Moreover, we show combinatorial effects with potential synergy for HSPC expansion by targeting the Aryl Hydrocarbon Receptor (AHR) in conjunction with members of the CoREST complex. Taken together, our traceable multiplexed CRISPR/Cas9 system enables studies of genetic dependencies and cooperation in primary HSPCs, and has important implications for modelling polygenic diseases, as well as investigation of the underlying mechanisms of gene interactions.

Abstract The CRISPR/Cas9 system is a versatile tool for functional genomics and forward genetic screens in mammalian cells. However, it has been challenging to deliver the CRISPR components to sensitive cell types, such as primary human hematopoietic stem and progenitor cells (HSPCs), partly due to lentiviral transduction of Cas9 being extremely inefficient in these cells. Here, to overcome these hurdles, we developed a combinatorial system using stable lentiviral delivery of single guide RNA (sgRNA) followed by transient transfection of Cas9 mRNA by electroporation in human cord blood-derived CD34+ HSPCs. We further applied an optimized sgRNA structure, that significantly improved editing efficiency in this context, and we obtained knockout levels reaching 90% for the cell surface proteins CD45 and CD44 in sgRNA transduced HSPCs. Our combinatorial CRISPR/Cas9 delivery approach had no negative influence on CD34 expression or colony forming capacity in vitro compared to non-treated HSPCs. Furthermore, gene edited HSPCs showed intact in vivo reconstitution capacity following transplantation to immunodeficient mice. Taken together, we developed a paradigm for combinatorial CRISPR/Cas9 delivery that enables efficient and traceable gene editing in primary human HSPCs, and is compatible with high functionality both in vitro and in vivo.

Background: The access to digital tools for parents is increasing, and further exploration is needed to gain knowledge about parents' experiences in using such tools, for example, when preparing for childbirth and parenthood. This study protocol describes a prospective study that will explore serious games as digital tools for parental support, and both parents' and healthcare professionals' views will be included. The objectives of the prospective study are to explore two different serious games: (1) Childbirth Journey (Swedish: Förlossningsresan), relating to pregnancy, childbirth and parenthood; and (2) Interplay (Swedish: Samspel), relating to parental couple relationships and parenthood.Methods: An intervention study will be conducted. The study will include four different sub-studies (A–D) with both qualitative and quantitative methods and a longitudinal design. Both parents (A, B and D) and healthcare professionals (C) will be included, and data will be collected through interviews (A–C) and repeated web-based questionnaires (D). Data will be analysed using phenomenography and qualitative content analysis (A–C), and descriptive and analytical analyses will be performed for comparisons and associations (D).Discussion: The value of monitoring and reporting on developments and trends in digital innovation for public health has been stipulated by the World Health Organization. The prospective study will contribute further knowledge about multidisciplinary development of digital tools as professional support for parents, as well as knowledge about parents' and healthcare professionals' experiences using digital tools concerning pregnancy, labour, parenthood and parental couple relationships.Trial Registration: This study was retrospectively registered (02/10/2020) within the ISRCTN with ID: ISRCTN18017741. http://www.isrctn.com/ISRCTN18017741.

Background: Parents use digital sources (such as the internet or online forums and applications) during pregnancy and after childbirth to receive informative support. Research shows that there is further need for innovation development in digital parental support despite informative support available in digital form.Purpose: To explore parents' perceptions of future digital parental support concerning pregnancy and the first 18 months of parenthood.Method: A phenomenographic interview study with an inductive approach including 15 semi-structured interviews was conducted.Results: The analysis process resulted in three descriptive categories: Opportunities for virtual and in-person meetings, Individualized digital parental support, and Professional knowledge and trustworthiness concerning future digital parental support.Conclusion: The results broaden the knowledge about how future digital parental support can be designed to facilitate the functional, interactive, and critical digital health literacy of new and would-be parents. To succeed, healthcare organizations should allow healthcare professionals to assume an active role in developing digital parental support, both as health educators (i.e., providing parents with knowledge) and facilitators (i.e., facilitating parents' use of digital parental support). However, parents perceived that future digital parental support should complement standard care instead of replacing in-person meetings with healthcare professionals.

Abstract Background Comorbidity of bipolar disorder and obsessive–compulsive disorder is common in adolescence. Obsessive–compulsive disorder symptoms may be episodic and secondary to alterations in mood, and display specific features. Management of pediatric bipolar disorder-obsessive–compulsive disorder is challenging, as pharmacotherapy of obsessive–compulsive disorder may induce or exacerbate manic episodes and there is limited evidence of treatment efficacy. Electroconvulsive therapy is sparsely used in children and adolescents, but is documented to be a safe and efficacious intervention in adults with bipolar disorder. In view of the severity of symptoms in juvenile mania, studies on treatment strategies are warranted. We report a case of an adolescent with bipolar disorder-obsessive–compulsive disorder who was successfully treated with electroconvulsive therapy during an episode of severe mania. Case presentation A 16-year-old girl of Middle East origin first presented to us with depressed mood, irritability, and increased obsessive–compulsive disorder symptoms, which were initially interpreted in the context of acute stress secondary to migration. She had been diagnosed with bipolar disorder and obsessive–compulsive disorder in her previous home country, but had difficulties in accounting for earlier psychiatric history. During hospitalization her mood switched to a manic state with mixed and psychotic features, at times showing aggression toward others. Interruption in her lithium treatment for a short period and possibly the introduction of an atypical antipsychotic could in part have been triggering factors. After 8 weeks of in-patient care and psychotropic drug trials, electroconvulsive therapy was initiated and administered every second or third day for 4 weeks, with marked positive response. No apparent side effects were reported. Conclusions This case demonstrates the need for a detailed medical history, taking special note of periodicity and character of obsessive–compulsive disorder symptoms, in adolescents with mood disorders. When treating culturally diverse patients, extra consideration should be taken. Special concerns in the pharmacological treatment to avoid the patient’s condition from worsening must be addressed, including giving priority to mood stabilization before obsessive–compulsive disorder symptoms. There are potential benefits in considering electroconvulsive therapy in young patients with severe mania where first-line treatment options have failed.

A computerized paradigm was created to allow for testing in the laboratory whether increasing systematicity helps the recruiter make better selection decisions. Participants were introduced to the job and the applicants on the computer screen and asked to select who they thought should be considered for the job and who should not. Level of systematicity, i.e. the extent to which the recruitment is methodical and uses prepared tools, was manipulated between subjects. Depending on experimental condition participants were helped by means of a tool for extracting judgment criteria (job analysis) and a tool for making judgments related to selected criteria (including calculation of a final score). The general prediction that increased systematicity leads to the selection of more qualified candidates was supported by the results, particularly when the motivation to put time and effort into the task was higher. The results support the claim from Industrial/Organizational psychologists that systematicity is a desirable characteristic in selection processes. The fact that increasing systematicity led to better selection decisions in a controlled laboratory experiment, along with process-related measures, suggests that this kind of paradigm could be useful when evaluating new tools for improving selection decisions, before they are tested in large (and costly) field studies of actual personnel selection.

Employment discrimination causes problems at the labor market, and is hard to combat. Can increasing the degree of structure when selecting applicants increase fairness? Students were asked to perform a computerized selection task and were either provided with tools for systematizing information about the applicants (structured selection) or no such tools (unstructured selection). We hypothesized and found that a structured process, where employing recruitment tools rather than the recruiter's impressionistic judgment is key, improves the ability to identify job-relevant criteria and hence selecting more qualified applicants, even when in-group favoritism is tempting (e.g. when the outgroup applicants are more competent). Increasing structure helped recruiters select more competent applicants and reduced ethnic discrimination. Increasing the motivation to carefully follow the structured procedure strengthened these effects further. We conclude that structure pays off, and that motivational factors should be taken into account in order for it to have the optimal effect.

Many biopharmaceuticals (BPs) are known to be immunogenic in the clinic, which can result in modified pharmacokinetics, reduced efficacy, allergic reactions and anaphylaxis. During recent years, several technologies to predict immunogenicity have been introduced, but the predictive value is still considered low. Thus, there is an unmet medical need for optimization of such technologies. The generation of T cell dependent high affinity anti-drug antibodies plays a key role in clinical immunogenicity. This study aimed at developing and evaluating a novel in vitro T cell:PBMC assay for prediction of the immunogenicity potential of BPs. To this end, we assessed the ability of infliximab (anti-TNF-α), rituximab (anti-CD20), adalimumab (anti-TNF-α) and natalizumab (anti-α4-integrin), all showing immunogenicity in the clinic, to induce a CD4+ T cells response. Keyhole limpet hemocyanin (KLH) and cytomegalovirus pp65 protein (CMV) were included as neo-antigen and recall antigen positive controls, respectively. By analyzing 26 healthy donors having HLA-DRB1 alleles matching the European population, we calculated the frequency of responding donors, the magnitude of the response, and the frequency of BP-specific T cells, as measured by 3[H]-thymidine incorporation and ELISpot IL-2 secretion. KLH and CMV demonstrated a strong T cell response in all the donors analyzed. The frequency of responding donors to the BPs was 4% for infliximab, 8% for adalimumab, 19% for rituximab and 27% for natalizumab, which is compared to and discussed with their respective observed clinical immunogenicity. This study further complements predictive immunogenicity testing by quantifying the in vitro CD4+ T cell responses to different BPs. Even though the data generated using this modified method does not directly translate to the clinical situation, a high sensitivity and immunogenic potential of most BPs is demonstrated.

Much of what we know concerning impression formation is based on experimental methods where the participant receives a list of traits or behaviors and is asked to make trait judgments or meta-cognitive judgments. The present study aimed to put some well-known effects from the impression formation literature to a test in a more dynamic computerized environment, more akin to many real world impression formation scenarios. In three studies participants were introduced to multiple target persons. They were given information about the target persons' behavior, one at a time, while making ratings of their warmth and competence, and their probability of performing related behaviors in the future. In neither of the studies the negativity effect of warmth or the positivity effect of competence were reproduced.

Many solution processing methods of exfoliation of layered materials have been studied during the last few years; most of them are based on organic solvents or rely on surfactants and other funtionalization agents. Pure water should be an ideal solvent, however, it is generally believed, based on solubility theories that stable dispersions of water could not be achieved and systematic studies are lacking. Here we describe the use of water as a solvent and the stabilization process involved therein. We introduce an exfoliation method of molybdenum disulfide (MoS2) in pure water at high concentration (i.e., 0.14 ± 0.01 g L-1). This was achieved by thinning the bulk MoS2 by mechanical exfoliation between sand papers and dispersing it by liquid exfoliation through probe sonication in water. We observed thin MoS2 nanosheets in water characterized by TEM, AFM and SEM images. The dimensions of the nanosheets were around 200 nm, the same range obtained in organic solvents. Electrophoretic mobility measurements indicated that electrical charges may be responsible for the stabilization of the dispersions. A probability decay equation was proposed to compare the stability of these dispersions with the ones reported in the literature. Water can be used as a solvent to disperse nanosheets and although the stability of the dispersions may not be as high as in organic solvents, the present method could be employed for a number of applications where the dispersions can be produced on site and organic solvents are not desirable.

Rape has been found to be the trauma most commonly associated with Posttraumatic Stress Disorder (PTSD) among women. It is therefore important to be able to identify those women at greatest risk of developing PTSD. The aims of the present study were to analyze the PTSD prevalence six months after sexual assaults and identify the major risk factors for developing PTSD.Participants were 317 female victims of rape who sought help at the Emergency Clinic for Raped Women at Stockholm South Hospital, Sweden. Baseline assessments of mental health were carried out and followed up after six months.Thirty-nine percent of the women had developed PTSD at the six month assessment, and 47% suffered from moderate or severe depression. The major risk factors for PTSD were having been sexually assaulted by more than one person, suffering from acute stress disorder (ASD) shortly after the assault, having been exposed to several acts during the assault, having been injured, having co-morbid depression, and having a history of more than two earlier traumas. Further, ASD on its own was found to be a poor predictor of PTSD because of the substantial ceiling effect after sexual assaults.Development of PTSD is common in the aftermath of sexual assaults. Increased risk of developing PTSD is caused by a combination of victim vulnerability and the extent of the dramatic nature of the current assault. By identifying those women at greatest risk of developing PTSD appropriate therapeutic resources can be directed.

In state-dependency, information retrieval is most efficient when the animal is in the same state as it was during the information acquisition. State-dependency has been implicated in a variety of learning and memory processes, but its mechanisms remain to be resolved. Here, mice deficient in AMPA-type glutamate receptor GluA1 subunits were first conditioned to morphine (10 or 20 mg/kg s.c. during eight sessions over four days) using an unbiased procedure, followed by testing for conditioned place preference at morphine states that were the same as or different from the one the mice were conditioned to. In GluA1 wildtype littermate mice the same-state morphine dose produced the greatest expression of place preference, while in the knockout mice no place preference was then detected. Both wildtype and knockout mice expressed moderate morphine-induced place preference when not at the morphine state (saline treatment at the test); in this case, place preference was weaker than that in the same-state test in wildtype mice. No correlation between place preference scores and locomotor activity during testing was found. Additionally, as compared to the controls, the knockout mice showed unchanged sensitization to morphine, morphine drug discrimination and brain regional μ-opioid receptor signal transduction at the G-protein level. However, the knockout mice failed to show increased AMPA/NMDA receptor current ratios in the ventral tegmental area dopamine neurons of midbrain slices after a single injection of morphine (10 mg/kg, s.c., sliced prepared 24 h afterwards), in contrast to the wildtype mice. The results indicate impaired drug-induced state-dependency in GluA1 knockout mice, correlating with impaired opioid-induced glutamate receptor neuroplasticity.

BackgroundDigital health technologies have the potential to transform health care services to be more cost-effective, coordinated, and accessible on equal terms for entire populations. In the future, people will be assisted by such technologies to monitor their health status, take preventive measures, and have more control of their health situation. An increase in digital supplementation or substitution of physical care visits can potentially add value to patients and care providers by increasing accessibility, safety, and quality of care. However, health care organizations struggle with the challenges of developing and implementing digital health technologies and services in practice. As a response to this, we have developed a national multidisciplinary research school to increase competence and capacity for research on the development, implementation, and dissemination of digital health technology solutions. The overall aim of the research school is to increase national competence and capacity for the development, implementation, and dissemination of digital health technology to increase the preparedness to support and facilitate the ongoing digital transformation in the health care system. ObjectiveThe purpose of this paper is to outline the protocol for the development and implementation of a national multidisciplinary doctoral education program of health innovation supporting digital transformation in the health care system. MethodsA national multidisciplinary research school for health innovation was planned in collaboration between 7 Swedish universities and their partners from industry and the public sector. The research school will run over 6 years, of which 5 years are dedicated for the doctoral education program and 1 year for the project start-up and closing. In this paper, we outline the methodological approach of the research school; the combining of knowledge and expertise of the universities that are important to run the research school; the jointly formulated research-oriented and societally relevant research focus, goals, and objectives for the research school; the established and developed relationships with partners from industry and the public sector for joint research training projects; the forms of collaboration in the research school; and the format of the doctoral education process. ResultsThe research school was funded in December 2021 and started in March 2022. The research school starts with an initiation period from March 2022 to December 2022 where the infrastructure and the action plans to run the school are set up. The PhD projects start in January 2023, and these projects will be completed in 5 years. Additional activities within the research program are doctoral courses, networking activities, and dissemination of results. ConclusionsThe network of several partners from industry, public sector, and academia enables the research school to pose research questions that can contribute to solving relevant societal problems related to the development, evaluation, implementation, and dissemination of methods and processes assisted by digital technologies. Ultimately, this will promote innovation to improve health outcomes, quality of care, and prioritizations of resources. International Registered Report Identifier (IRRID)PRR1-10.2196/46595

BackgroundGlobally, the digital sources developed and available in antenatal care differ, and infrastructure challenges may impede the further development of such sources. Challenges accompanying digital developments can include the commonly occurring high workload, which affects healthcare professionals' ability to acquire professional knowledge about how to best support parents in using digital sources. Including healthcare professionals in the development process of digital sources may increase the likelihood that such sources will be adopted and employed by these professionals in their future care work. Therefore, the present research explored healthcare professionals' perceptions of the digital support intervention Childbirth Journey, which was constructed as a serious game for expectant parents.MethodsData were collected through semi-structured focus-group interviews with 11 midwives at antenatal, labour and postnatal clinics as well as with child healthcare nurses. Prior to the interviews, all participants were provided the intervention, Childbirth Journey, which is a serious game in a mobile application format consisting of two distinct parts: (1) a story-driven game and (2) a Knowledge Portal. The data were analysed using phenomenographic methods.ResultsThe perceptions of Childbirth Journey by healthcare professionals, midwives and child healthcare nurses are presented in four descriptive categories: extended professional support, trustworthy contents, diversity or individuality, and both appealing and in need of development.ConclusionsCurrent study revealed that Childbirth Journey may be utilised as a digital support for parents, allowing healthcare professionals to offer a digital solution as a complementary support to standard, face-to-face meetings with caregivers. However, the research results also revealed that some elements of Childbirth Journey must be improved, thereby representing a main contribution of this study: insights into how to better develop digital tools under the umbrella of health care. Thus, we conclude that in order to create sustainable and safe digital care solutions that function as trustworthy professional supports instead of technical products that risk harming users, the perspectives of both patients and healthcare professionals should be considered in the exploration and development of these solutions.