Dominant negative variants and cotranslational assembly of macromolecular complexes.

Pathogenic variants occurring in protein-coding regions underlie human genetic disease through various mechanisms. They can lead to a loss of function (LOF) such as in recessive conditions or in dominant conditions due to haploinsufficiency. Dominant-negative (DN) effects, counteracting the activity of the normal gene-product, and gain of function (GOF) are also mechanisms driving dominance. Here, I discuss a few papers on these specific mechanisms. In short, there is accumulating evidence pointing to differences between LOF versus non-LOF variants (DN and GOF). The latter are thought to have milder effects on protein structure and, as expected, DN variants are enriched at protein interfaces. This tendency to cluster in 3D space can help improve the ability of computational tools to predict the pathogenicity of DN variants, which is currently a challenging issue. More recent results support the hypothesis whereby cotranslational assembly of macromolecular complexes can buffer deleterious consequences of variants that would otherwise lead to DN effects (DNEs). Indeed, subunits the variants of which are responsible for DNEs tend to elude cotranslational assembly, thus poisoning complexes involving wild-type subunits. The constraints explaining why the buffering of DNEs is not universal require further investigation.

The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy.

The endoplasmic reticulum (ER) employs stringent quality control mechanisms to ensure the integrity of protein folding, allowing only properly folded, processed and assembled proteins to exit the ER and reach their functional destinations. Mutant proteins unable to attain their correct tertiary conformation or form complexes with their partners are retained in the ER and subsequently degraded through ER-associated protein degradation (ERAD) and associated mechanisms. ER retention contributes to a spectrum of monogenic diseases with diverse modes of inheritance and molecular mechanisms. In autosomal dominant diseases, when mutant proteins get retained in the ER, they can interact with their wild-type counterparts. This interaction may lead to the formation of mixed dimers or aberrant complexes, disrupting their normal trafficking and function in a dominant-negative manner. The combination of ER retention and dominant-negative effects has been frequently documented to cause a significant loss of functional proteins, thereby exacerbating disease severity. This review aims to examine existing literature and provide insights into the impact of dominant-negative effects exerted by mutant proteins retained in the ER in a range of autosomal dominant diseases including skeletal and connective tissue disorders, vascular disorders, neurological disorders, eye disorders and serpinopathies. Most crucially, we aim to emphasize the importance of this area of research, offering substantial potential for understanding the factors influencing phenotypic variability associated with genetic variants. Furthermore, we highlight current and prospective therapeutic approaches targeted at ameliorating the effects of mutations exhibiting dominant-negative effects. These approaches encompass experimental studies exploring treatments and their translation into clinical practice.

Actions for mitigating the negative effects of patient participation in patient safety: a qualitative study.

BACKGROUND: Recent research within the context of Obstetrics shows the added value of patient participation in in-hospital patient safety. Notwithstanding these benefits, recent research within an Obstetrics department shows that four different negative effects of patient participation in patient safety have emerged. However, the approach to addressing these negative effects within the perspective of patient participation in patient safety is currently lacking. For this reason, the aim of this study is to generate an overview of actions that could be taken to mitigate the negative effects of patient participation in patient safety within an Obstetrics department. METHODS: This study was conducted in the Obstetrics Department of a tertiary academic center. An explorative qualitative interview study included sixteen interviews with professionals (N = 8) and patients (N = 8). The actions to mitigate the negative effects of patient participation in patient safety, were analyzed and classified using a deductive approach. RESULTS: Eighteen actions were identified that mitigated the negative effects of patient participation in patient safety within an Obstetrics department. These actions were categorized into five themes: 'structure', 'culture', 'education', 'emotional', and 'physical and technology'. These five categories reflect the current approach to improving patient safety which is primarily viewed from the perspective of professionals rather than of patients. CONCLUSIONS: Most of the identified actions are linked to changing the culture to generate more patient-centered care and change the current reality, which looks predominantly from the perspective of the professionals and too little from that of the patients. Furthermore, none of the suggested actions fit within a sixth anticipated category, namely, 'politics'. Future research should explore ways to implement a patient-centered care approach based on these actions. By doing so, space, money and time have to be created to elaborate on these actions and integrate them into the organizations' structure, culture and practices.

Internet- and mobile-based anxiety and depression interventions for children and adolescents: efficacy and negative effects - a systematic review and meta-analysis.

Mental disorders, most commonly anxiety disorders and fourth most common depression, are prevalent in children and adolescents. Internet- and mobile-based interventions might represent a scalable approach to improve mental health care, however, evidence so far is inconclusive and systematic reports on negative effects are missing. Four data-bases were searched for randomized controlled trials evaluating internet- and mobile-based interventions (IMIs) targeting anxiety disorders or depression in children and adolescents up to 18 years exhibiting clinically relevant symptoms. Meta-analytic evaluations were conducted in comparison to active and passive control groups, furthermore, pre-defined sub-groups were explored and reported negative effects examined. Pooled estimates showed a moderate positive effect for IMIs targeting anxiety disorders compared to passive control groups (g = -0.69; CI -0.94 to -0.45; k = 8; n = 559; p ≤ 0,001), but not for depression. Pooled estimates compared to active control groups remained non-significant. Subgroup analyses were largely omitted due to an insufficient number of trials or were non-significant. Negative effects were mainly reported as drop-out rates and (non)-response rates, while additional negative effects, such as deterioration rates or the development of additional symptoms, were reported by only one third of included studies. The focus on children and adolescents with clinically relevant symptoms allowed the present findings to complement previous work, however, the limited amount of trials hindered many planned comparisons. The overview of reported negative effects highlighted that negative effects are being neglected in the majority of RCTs. Hence, in the future RCTs should include more information about potential negative effects, at best a combination of quantitative and qualitative information. Open Science Framework (osf.io/ch5nj).

Better Safe Than Sorry. A Scoping Review of Monitoring for Negative Effects in Preregistrations of Psychological Interventions.

Although negative effects of psychological interventions are suspected to be common, they are rarely investigated. Experts and international guidelines agree that monitoring for negative effects in clinical studies is needed to make psychological interventions safer and to empower patients before they give their consent to participate. Therefore, monitoring should already be considered during planning and preregistration of a study. The aim of this scoping review was to find out how frequently studies on psychological interventions monitor their negative effects according to preregistrations and to investigate reasons why monitoring is not carried out. Preregistrations of psychological interventions on ClinicalTrials.gov were scrutinized for information on monitoring of negative effects and other study characteristics. In a survey, researchers of studies where no monitoring was reported were asked for reasons for not doing so. Overall, 2231 preregistrations of psychological interventions were found; of these, only 3.4% included explicit information on monitoring for negative effects. In the survey, more researchers reported having conducted monitoring, although the type of monitoring was often inadequate. The type of monitoring varied widely, and specific monitoring measurements were rarely used repeatedly. Monitoring for negative effects was more prevalent in studies investigating treatments versus low-threshold interventions, in studies conducted in Europe versus other continents and in more recent studies. Researchers reported lack of knowledge as the most frequent reason for not monitoring negative effects. Our results imply a lack of monitoring and inconsistent information on negative effects in preregistrations, with inconsistent use of the term monitoring and measurements, and a lack of knowledge among researchers. Improved knowledge and a standardized approach, starting with an adequate preregistration, would be helpful to routinely examine negative effects in psychological interventions to make them safer and better.

Negative effects in randomized controlled trials of psychotherapies and psychological interventions: A systematic review.

Background: Psychotherapy is a key evidence-based method for the treatment of mental disorders. However, little research has been published on the negative effects of psychotherapies. Aims: We examined this issue through a systematic literature review of previous systematic reviews on randomized controlled trials (RCTs). Methods: We focused on previous reviews and meta-analyses on 1) RCTs examining the effectiveness of psychotherapies and 2) previous reviews and meta-analyses specifically focusing on the negative effects of psychotherapy. We included publications published in PubMed and the Cochrane Databases from the year 2000 or later. Results: Of the 1,430 relevant publications, only a small proportion (30%) mentioned negative outcomes, mostly withdrawal. Only 57 of the extracted original studies monitored potential negative effects, and only three small-scale studies indicated negative effects. Conclusions: The systematic monitoring of negative effects in psychotherapy has not been given the same attention as has been given to the benefits of therapy.

Gene Augmentation for Autosomal Dominant CRX-Associated Retinopathies.

The cone-rod homeobox (CRX) protein is a key transcription factor essential for photoreceptor function and survival. Mutations in human CRX gene are linked to a wide spectrum of blinding diseases ranging from mild macular dystrophy to severe Leber congenital amaurosis (LCA), cone-rod dystrophy (CRD), and retinitis pigmentosa (RP). These diseases are still incurable and mostly inherited in an autosomal dominant form. Dysfunctional mutant CRX protein interferes with the function of wild-type CRX protein, demonstrating the dominant negative effect. At present, gene augmentation is the most promising treatment strategy for hereditary diseases. This study aims to review the pathogenic mechanisms of various CRX mutations and propose two therapeutic strategies to rescue sick photoreceptors in CRX-associated retinopathies, namely, Tet-On-hCRX system and adeno-associated virus (AAV)-mediated gene augmentation. The outcome of proposed studies will guide future translational research and suggest guidelines for therapy evaluation in terms of treatment safety and efficacy.

Microplastic migration and distribution in the terrestrial and aquatic environments: A threat to biotic safety.

Plastics production has been increasing over years, while their recycling rate is lower, resulting in huge amounts of microplastics (MP) accumulating in the environment. Although the environmental behaviors of MPs have been focused on in recent years, the migration, distribution and adverse effects of MPs in terrestrial and aquatic environments are still not systematically understood. In this review, based on the newest publications from the core database of the Web of Science, both the migration and distribution of MPs were summarized, as well as MPs transfer in biota and their biological effects were also focused on. Generally, the complicated and numerous pathways of MPs migration lead to their distribution throughout or nearly all environments on a global scale. However, the migration mechanisms of MPs with various sizes, shapes, and colors by physicochemical and biological processes, and the prediction models of MP migration and distribution, are deficient, despite these properties being highly related to MPs migration and bio-safety. Although MPs have already invaded microorganisms, plants, animals, and even human beings, the biological effects still need more study, so far as their sizes and shapes and also their composition and adsorption are concerned. Moreover, based on the highlights and deficiencies of current studies, further studies have also been proposed. This review aims to help people re-evaluate the uncertain behaviors of MPs in various environments, and could be helpful to fully understand their biological effects in different environmental conditions.

Could negative outcomes of psychotherapies be contributing to the lack of an overall population effect from the Australian Better Access initiative?

OBJECTIVE: We examine deterioration in psychotherapies, as reported in the recent evaluation of the Australian Medicare Better Access initiative. CONCLUSION: A focus on patients who experience poor clinical outcomes helps programs minimise harm and improve quality of care. The Better Access evaluation found the mental health of 20-40% of patients deteriorated. This may partly explain why population distress and suicide rates were not reduced by the introduction of the Better Access initiative. Deterioration was more likely for milder conditions, and less likely for severe conditions, which also improved the most. Using severity as a criterion for priority setting and resource allocation may minimise patient risk and maximise benefits. Patients with severe conditions may require considerably more sessions than the current average for Better Access psychotherapies.

Informing patients about possible negative effects of psychological treatment: A survey of Swedish clinical psychologists' attitudes and practices.

OBJECTIVE: The present study explored Swedish clinical psychologists' attitudes and practices of informing patients about possible negative effects of psychological treatment. METHOD: An anonymous online survey with closed and open-ended questions was distributed via Facebook and two mailing lists. In total, 320 clinical psychologists (age M = 38.6, SD = 10.3; 76% women; 77.3% Cognitive Behavior Therapy) completed the survey. Responses were analyzed using χ2, binominal regression analysis, and thematic analysis. RESULTS: No significant associations were identified between demographic variables selected a priori and informing patients about possible negative effects, i.e., years in practice, therapeutic orientation, age, and male gender. The thematic analysis resulted in several positive (e.g., creating realistic expectations of treatment and increasing resilience) and negative attitudes (e.g., causing excessive worry) of sharing patients with information about possible negative effects. It also revealed various factors that prevent an open discussion on the topic, despite being seen as important. CONCLUSION: The need to offer patients information about possible negative effects should be included in ethical guidelines, codes of conduct, and taught during clinical training. Lack of knowledge, fear, lack of time, and patient characteristics however seem to prevent therapists from discussing the issue during the informed consent procedure.

Negative effects during multicomponent group-based treatment: A multisite study.

Objective Negative effects (NEs) in group treatments remain an under-researched area. This study aimed to explore the prevalence of various types of NEs in a multicomponent group-based treatment and to determine their predictors. Method: A total of 330 patients participating in a multicomponent group-based treatment were recruited across seven clinical sites. At the end of treatment, the Negative Effects Questionnaire (NEQ) was used to measure NEs. Item-level descriptive analysis was conducted to explore the prevalence of various types of NEs, and structural equation modeling was used to determine predictors of these NEs. Results: The most frequently reported type of NEs was the worsening of symptoms, and the single most frequently reported item was the resurfacing of unpleasant memories. Predictors of NEs included the overall distress level, alexithymia, attachment avoidance, low working alliance, problem actuation, and worse outcomes; psychological mindedness was a protective factor. Conclusion: Patients who experience higher levels of distress at the beginning of treatment, who perceive the group working alliance as problematic, and who experience high in-session emotional arousal related to their problem seem to be especially prone to reporting NEs. Furthermore, the findings do not support the assumption that NEs are a prerequisite for therapeutic change.Trial registration: ISRCTN.org identifier: ISRCTN13532466.

Predictors of Client Satisfaction With Bereavement Counselling: The Role of Negative Effects.

Bereaved persons seeking help in bereavement counselling report generally high client satisfaction. However, qualitative research suggests that some clients also indicate dissatisfying experiences and negative effects. The aim of this study was to investigate the contribution of content-, counsellor- and client-related characteristics and negative effects to client satisfaction. Bereaved participants (n = 53) who had completed bereavement counselling were recruited either online or via counselling organizations. In an online survey, they provided information about client-, loss- and counselling-related variables, present grief severity, negative effects of counselling and client satisfaction. In a hierarchical linear regression analysis controlling for recruitment strategy, online-recruited participants were less satisfied. In a second step additionally considering number of sessions, grief severity and negative effects, experiencing more negative effects predicted lower client satisfaction. The results indicate that negative effects could play an important role for client satisfaction. More research is needed to investigate this phenomenon.

Unintended Consequences of Plant Domestication.

Human selection on wild populations mostly favored a common set of plant traits during domestication. This process of direct selection also altered other independent traits that were not directly perceived or desired during crop domestication and improvement. A deeper knowledge of the inadvertent and undesirable phenotypic effects and their underlying genetic causes can help design strategies to mitigate their effects and improve genetic gain in crop plants. We review different factors explaining the negative consequences of plant domestication at the phenotypic and genomic levels. We further describe the genetic causes of undesirable effects that originate from the selection of favorable alleles during plant domestication. In addition, we propose strategies that could be useful in attenuating such effects for crop improvement. With novel -omics and genome-editing tools, it is relatively approachable to understand and manipulate the genetic and biochemical mechanisms responsible for the undesirable phenotypes in domesticated plants.

Risk or benefit? Side effects of caffeine supplementation in sport: a systematic review.

PURPOSE: The aim of this study was to systematically review evidence on the prevalence and magnitude of side effects associated with caffeine supplementation in athletes. METHODS: Systematic searches through the PubMed, VHL, Scopus, and Web of Science databases were conducted according to the PRISMA guidelines. Peer-reviewed articles written in English that reported the prevalence/percentage or magnitude/effect size of side effects after caffeine supplementation in athletes in a sports context were included. Studies were grouped by the dose of caffeine administered as follows: low = ≤ 3.0 mg/kg; moderate = from 3.1 to 6.0 mg/kg; high = ≥ 6.1 mg/kg. The magnitude of the side effects was calculated with effect sizes. RESULTS: The search retrieved 25 studies that met the inclusion/exclusion criteria with a pooled sample of 421 participants. The supplementation with caffeine produced a higher prevalence or magnitude of all side effects under investigation when compared to placebo/control situations. The prevalence (magnitude) was between 6 and 34% (ES between 0.13 and 1.11) for low doses of caffeine, between 0 and 34% (ES between -0.13 and 1.20) for moderate doses of caffeine, and between 8 and 83% (ES between 0.04 and 1.52) with high doses of caffeine. The presence of tachycardia/heart palpitations and the negative effects on sleep onset had the highest prevalence and magnitude, in athletes using supplementation with caffeine. CONCLUSION: In summary, caffeine supplementation in the doses habitually used to enhance physical performance produces several side effects, both after exercise and at least 24 h after the ingestion. However, the prevalence and magnitude of side effects with high doses of caffeine were habitually higher than with low doses of caffeine. From a practical perspective, using ~3.0 mg/kg of caffeine may be the dose of choice to obtain the ergogenic benefits of caffeine with the lowest prevalence and magnitude of side effects.

Efficacy, Benefits, and Harms of a Self-management App in a Swedish Trauma-Exposed Community Sample (PTSD Coach): Randomized Controlled Trial.

BACKGROUND: Self-guided interventions may complement and overcome obstacles to in-person treatment options. The efficacy of app interventions targeting posttraumatic stress disorder (PTSD) is unclear, and results from previous studies on PTSD Coach-an app for managing trauma-related distress-are inconsistent. OBJECTIVE: This study investigates whether access to the Swedish version of the PTSD Coach affects posttraumatic stress, depressive, and somatic symptoms. In addition, we aim to assess the perceived helpfulness, satisfaction, negative effects, response, and remission related to PTSD Coach. METHODS: Adults who had experienced potentially traumatic events in the past 2 years were randomized (1:1) to have access to PTSD Coach (n=89) or be on the waitlist (n=90). We assessed clinical characteristics at baseline (semistructured interviews and self-rating scales) and after 3 months (self-rating scales). We analyzed the data in R software using linear mixed effects models, chi-square tests, and Fisher exact test. RESULTS: Intention-to-treat analyses indicated that access to PTSD Coach decreased posttraumatic stress and depressive symptoms but not somatic symptoms. More participants who had access to PTSD Coach responded with clinically significant improvement and fewer instances of probable PTSD after 3 months compared with waitlist controls. Overall, participants found that PTSD Coach was slightly to moderately helpful and moderately satisfactory. Half of the intervention group (36/71, 51%) reported at least one negative reaction related to using PTSD Coach (eg, disappointment with the app or its results, arousal of stress, or distressing memories). CONCLUSIONS: Using PTSD Coach may trigger symptoms among a few users; however, most of them perceived PTSD Coach as helpful and satisfactory. This study showed that having access to PTSD Coach helped improve psychological trauma-related symptoms. In addition, we have discussed implications for future research and clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094922; https://clinicaltrials.gov/ct2/show/NCT04094922.

[Analysis of the principles of Tibetan medicine processing].

Tibetan medicine processing ensures the safety of clinical application of Tibetan medicine. It is of great significance to analyze the principles of Tibetan medicine processing in the development, inheritance, and innovation of Tibetan medicine. However, due to the late start of modern Tibetan medicine research and the disciplinary division, the current research on Tibetan medicine processing focuses on the exploration and collation of traditional techniques and the analysis of the processing mechanism of Tibetan medicine through chemical and pharmacological research, but its principles and traditional theories have been rarely reported. In view of this, after analyzing the concept, essence, theories, purposes, and functions of Tibetan medicine processing through the integration of Tibetan medicine, Tibetan pharmacology, and clinical research of Tibetan medicine, this study proposed that the essence of Tibetan medicine processing was to change the "five sources" composition of medicinal materials through physical, chemical, and biological means, or the comprehensive means, and the theoretical principle of Tibetan medicine processing was to change or transform the positive and adverse effects or the obvious and recessive effects by altering the "five sources" composition of the drug to maximize the positive effect and minimize the adverse effect and the damage to the body, thereby achieving the purposes of toxicity reduction, efficacy enhancement, and drug property harmonization represented by sharpening, softening, nourishing, and reasonable compatibility. This study is expected to provide references for the construction of the theoretical system of Tibetan medicine processing, the inheritance of processing techniques, and innovative research.

The Analgesic Effects of Static Magnetic Fields.

Pain is one of the most common reasons why people seek medical care, which is related to most disease states. Magnetic fields (MFs) can be applied locally to specific parts of human bodies with high penetration and temporal control, which have a long-debated history in folk therapy. The purpose of this review is to collect and analyze experimental data about the analgesic effects of static magnetic fields (SMFs) so that we can have a scientific understanding regarding this topic. We collected 28 studies (25 English and 3 Chinese papers) with proper sham controls that investigated the effects of SMFs on pain relief in humans or mice. We found that 64% of the human studies and all mice studies in the literature showed positive analgesic effects of SMFs, which are related to factors including SMF intensity, treatment time, and pain types. Higher intensity and/or longer treatment time, as well as some specific pain types, may have better pain relief effects. Initial mechanistic studies indicated that membrane receptors, such as capsaicin receptor VR1/TRPV1, opioid receptors, and P2X3 receptors, might be involved. By describing experimental evidence and analysis, we found that SMFs actually hold considerable promise for managing some specific types of pain if proper SMF parameters are used. More studies comprehensively evaluating the parameters of SMF and its corresponding analgesic effects on different pain types, as well as the underlying molecular mechanisms, will be necessary to further validate its therapeutic potential in pain management in the future. Bioelectromagnetics. 00:00-00, 2021. © 2021 Bioelectromagnetics Society.

Potential effects of umami ingredients on human health: Pros and cons.

Umami taste is the most recent confirmed basic taste in addition to sour, sweet, bitter, and salty. It has been controversial because of its effects on human nutritional benefit. Based on the available literatures, this review categorized 13 positive and negative effects of umami taste on human health. On the positive side, umami taste can improve food flavor and consumption, improve nutrition intake of the elderly and patients, protect against duodenal cancer, reduce ingestion of sodium chloride, decrease consumption of fat, and improve oral functions. On the other hand, umami taste can also induce hepatotoxicity, cause asthma, induce migraine headaches, damage the nervous system, and promote obesity. Due to its novelty, there are many functions and effects of umami taste waiting to be discovered. With further investigation, more information regarding the effects of umami taste on human health will be discerned.

Standardized multimodal intervention for stress-induced exhaustion disorder: an open trial in a clinical setting.

BACKGROUND: Long-term sick-leave due to stress-related ill-health is increasing in several economically developed countries. Even though different forms of interventions are administered in regular care for stress-related disorders, such as Stress-induced Exhaustion disorder (SED), the scientific evidence for the effectiveness of such treatments is sparse. The objective of this study was to explore changes in SED-symptoms and return-to-work-rates in a large group of SED-patients participating in a standardized Multimodal intervention (MMI) in a clinical setting. METHOD: This open clinical trial tracked 390 patients who fulfilled the criteria for SED undergoing a 24-week MMI, including return-to-work-strategies. Before inclusion, all patients underwent a multi-professional assessment by a team of licensed physicians, licensed psychologists, and licensed physiotherapists. Self-rated questionnaires were administered before treatment, at treatment-start, mid-treatment, post-treatment, and at 12-month follow-up. Within-group change was evaluated over time with mixed-effects models. Beyond different symptoms, working time, sick-leave compensation, and adverse effects were also measured. RESULTS: There were significant improvements in symptoms of SED, burnout, anxiety, depression, and insomnia, with large within-group effect sizes (d = 0.91-1.76), improvements that were maintained at 12-month follow-up. Furthermore, there was a significant increase in quality of life and large improvements in average working time and sick-leave compensation. Some adverse effects were reported, mainly concerning an increase in stress, anxiety, and worry. CONCLUSION: SED-patients participating in this standardized MMI reported large symptom alleviation, increased working time and reduced sick-leave compensation, indicating a beneficial treatment. There were some adverse effects, but no more so than other psychological treatments. This study confirms previous findings that high levels of depression and anxiety decrease to sub-clinical levels during treatment, while symptoms of SED also decline, yet still persists above sub-clinical levels at 12-month follow-up. On the whole, this open clinical trial suggests that a standardized MMI, administered in a clinical setting, improves symptoms and return-to-work rates in a clinically representative SED-population. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov 2017.12.02 (Identifier: NCT03360136 ).

Adaptation of the negative effects questionnaire into the Czech context.

Objective: The aim of this study was to adapt the Negative Effects Questionnaire (NEQ) into the Czech context and to assess its psychometric properties as well as the extent to which it covers important areas of the negative aspects of psychotherapy. Method: A total of 226 respondents answered an online survey. Confirmatory and exploratory factor analyses were conducted to assess the NEQ factor structure. Thematic analysis was used to analyze the open-ended NEQ item. Results: In terms of confirmatory factor analysis, the six-factor model proposed by the authors of the NEQ did not demonstrate an adequate fit. In a subsequent exploratory factor analysis, a more parsimonious, five-factor solution was proposed instead. Furthermore, a thematic analysis revealed some areas underrepresented in the NEQ, particularly clients' relationships with their relatives. Conclusions: The NEQ is a reliable instrument with a high added value for research and practice. Several directions for future development are suggested.