A follow-up study of first episode major depressive disorder. Impairment in inhibition and semantic fluency—potential predictors for relapse?

The present study investigated the Executive Functions (EF) of inhibition, mental flexibility and phonemic and semantic fluency in a 1-year follow-up assessment of patients diagnosed with first episode Major Depressive Disorder (MDD). In the acute phase, the patient group performed significantly poorer compared to the control group (CG) in inhibition and semantic fluency. The present study pursued these findings from the acute phase to see if the impairment seen in inhibition and semantic fluency in the acute phase normalized or persisted in the follow-up assessment. In addition, the present study investigated the association between poor inhibition and semantic fluency performance and the experience of relapse during the 1-year period. Twenty eight patients and 28 individually matched control subjects were included. EF was reassessed using three tests from the Delis Kaplan Executive Function System (D-KEFS). Results : There was a significant decrease in depression severity score from the acute phase, showing that most of the patients were in remission in the follow-up assessment. Results showed a sustained impairment in inhibition and semantic fluency in the patient group. However, the performance in inhibition was more severe when an additional requirement of mental flexibility was included. There were no group differences in the other EF functions measured. Further, patients with a relapse in the course of 1 year performed significantly poorer in inhibition/switching at inclusion compared to patients that did not relapse and the CG. This relationship was not found for semantic fluency. Poor performance in inhibition and semantic fluency are prolonged despite symptom reduction in patients with a first episode of MDD. Moreover, although based on a small sample of patients, the present study showed that there may be a relationship between impaired ability in the EF of inhibition/switching and vulnerability for the experience of relapse.publishedVersio

Inhibitory control as possible risk and/or resilience factor for the development of trauma related symptoms–a study of the Utøya terror attack survivors

PTSD symptomatology is known to be associated with executive dysfunction. Inhibitory control is a core component of executive functioning, and inhibitory skills are essential both for adequate functioning in everyday life and important in situations following trauma. The aim of the present study was to examine the relationship between trauma exposure, inhibitory control and PTSD symptomatology in adolescent survivors of the terror attack at Utøya, Norway on the 22nd of July, 2011. In this cross-sectional case-control study, 20 trauma exposed adolescents and 20 healthy controls matched in age and gender were compared on a neuropsychological test of cognitive inhibition (Color-Word Interference Test) and a self-report measure of inhibition ability (BRIEF-A). Our analyses revealed that the trauma exposed group differed significantly on the self-reported measure of inhibitory control compared to the control group, but there were no differences between groups on the objective measures of cognitive inhibition. Follow-up analyses with subgroups in the trauma exposed group based on PTSD symptomatology (PTSD + and PTSD-) and the control group revealed that the PTSD- group showed significantly better results than both the PTSD + and the control group on the measures of inhibitory control. Moreover, the follow-up analyses showed that the PTSD + group showed significantly poorer results from the other two groups on the measures of inhibitory control and self-reported inhibition. We conclude that impaired inhibitory control, measured both objectively and by self-reported questionnaire, is related to PTSD symptomatology. Findings suggest that inhibitory dysfunctions may be a vulnerability factor for the development of PTSD symptomatology in trauma exposed adolescents, and thus it seems that the ability to exhibit inhibitory control could be a possible resilience factor to prevent the development of PTSD symptoms.publishedVersio

Identification of novel cyanoacrylate monomers for use in nanoparticle drug delivery systems prepared by miniemulsion polymerisation – A multistep screening approach

Poly (alkyl cyanoacrylate) (PACA) polymeric nanoparticles (NPs) are promising drug carriers in drug delivery. However, the selection of commercially available alkyl cyanoacrylate (ACA) monomers is limited, because most monomers were designed for use in medical and industrial glues and later repurposed for drug encapsulation. This study therefore aimed to seek out novel ACA materials for use in NP systems using a toxicity led screening approach. A multistep strategy, including cytotoxicity screening of alcohols as degradation products of PACA (44 alcohols), NPs (14 polymers), and a final in vivo study (2 polymers) gave poly (2-ethylhexyl cyanoacrylate) PEHCA as a promising novel PACA candidate. For the first time, this work presents cytotoxicity data on several novel ACAs, PEHCA in vivo toxicity data, and miniemulsion polymerisation-based encapsulation of the cabazitaxel and NR688 in novel PACA candidates. Furthermore, several of the ACA candidates were compatible with a wider selection of lipophilic active pharmaceutical ingredients (APIs) versus commercially available controls. Combined, this work demonstrates the potential benefits of expanding the array of available ACA materials in drug delivery. Novel ACAs have the potential to encapsulate a wider range of APIs in miniemulsion polymerisation processes and may also broaden PACA applicability in other fields.publishedVersio

Place of residence and coach-athlete relationship predict drop-out from competitive cross-country skiing

The current study investigated whether factors such as living residence, the coach-athlete working alliance, goal orientation, and intrinsic motivation could explain drop-out, and whether these factors differed between athletes included in the elite- vs. general sport programs during high school years. In total 257 cross-country skiers, graduated from three different Norwegian Top Sport schools during the period from 2015 to 2019, were recruited to retrospectively investigate their experiences related to the time period when they participated in programs for cross-country skiing at high school. In total 116 of these athletes completed an online survey including validated and standardized instruments for the assessment of the coach-athlete working alliance (CAWAI), goal orientation (GO), perceived satisfaction with their performances (PAP) and intrinsic motivation (IM). The results showed that 84% of the athletes had dropped out from cross-country skiing, while 16% were still active. The highest ranked fixed statements of causes for drop-out was “a natural choice” (3.79 ± 1.11), “priority of education or work” (3.61 ± 1.30), “lack of motivation” (3.49 ± 1.28), “negative performance development” (3.46 ± 1.18), and “challenges with health” (3.25 ± 1.54). There were significant differences between active and drop-out in scores for reciprocity between the coaches' and the athletes' perceptions of goals (CAWAI-goal; 5.87 ± .98 vs. 5.07 ± 1.15; p = .004), the coach-athlete relationship bond (CAWAI-bond; 6.08 ± .91 vs. 5.07 ± 1.38; p = .001), and tasks chosen to reach the defined goals (CAWAI-task; 5.61 ± .92 vs. 4.90 ± 1.09; p = .006). Furthermore, active athletes had higher mastery orientation (22.11 ± 2.88 vs. 20.00 ± 3.74; p = .010). A hierarchical binary logistic regression analysis showed that place of residence and the coach-athlete working alliance were significant predictors of drop-out while mastery and performance goal orientation or intrinsic motivation were not significant. All five predictors explained 23% of the variability in drop out from cross-country skiing. Overall, 58% and 42% of the athletes participated in the elite and general programs for cross-country skiing during high school, respectively. The athletes that took part in the elite programs reported significantly stronger coach-athlete working alliances (CAWAI-sum; 14.46±3.10 vs. 14.28±3.37; p = .000), higher mastery orientation (21.19±3.50 vs. 19.36±3.66; p = .008), and performance satisfaction (PAP; 19.17±5.98 vs. 15.69±5.19; p = .001) compared to the athletes attending general programs. The results are discussed in terms of existing knowledge on how place of residence, the coach-athlete working alliance, goal orientation, performances, and motivation might impact drop-out in cross-country skiing

Interlaboratory evaluation of a digital holographic microscopy–based assay for label-free in vitro cytotoxicity testing of polymeric nanocarriers

State-of-the-art in vitro test systems for nanomaterial toxicity assessment are based on dyes and several staining steps which can be affected by nanomaterial interference. Digital holographic microscopy (DHM), an interferometry-based variant of quantitative phase imaging (QPI), facilitates reliable proliferation quantification of native cell populations and the extraction of morphological features in a fast and label- and interference-free manner by biophysical parameters. DHM therefore has been identified as versatile tool for cytotoxicity testing in biomedical nanotechnology. In a comparative study performed at two collaborating laboratories, we investigated the interlaboratory variability and performance of DHM in nanomaterial toxicity testing, utilizing complementary standard operating procedures (SOPs). Two identical custom-built off-axis DHM systems, developed for usage in biomedical laboratories, equipped with stage-top incubation chambers were applied at different locations in Europe. Temporal dry mass development, 12-h dry mass increments and morphology changes of A549 human lung epithelial cell populations upon incubation with two variants of poly(alkyl cyanoacrylate) (PACA) nanoparticles were observed in comparison to digitonin and cell culture medium controls. Digitonin as cytotoxicity control, as well as empty and cabazitaxel-loaded PACA nanocarriers, similarly impacted 12-h dry mass development and increments as well as morphology of A549 cells at both participating laboratories. The obtained DHM data reflected the cytotoxic potential of the tested nanomaterials and are in agreement with corresponding literature on biophysical and chemical assays. Our results confirm DHM as label-free cytotoxicity assay for polymeric nanocarriers as well as the repeatability and reproducibility of the technology. In summary, the evaluated DHM assay could be efficiently implemented at different locations and facilitates interlaboratory in vitro toxicity testing of nanoparticles with prospects for application in regulatory science.publishedVersio

Magnetic-Responsive Carbon Nanotubes Composite Scaffolds for Chondrogenic Tissue Engineering

The demand for engineered scaffolds capable of delivering multiple cues to cells continues to grow as the interplay between cell fate with microenvironmental and external cues is revealed. Emphasis has been given to develop stimuli-responsive scaffolds. These scaffolds are designed to sense an external stimulus triggering a specific response (e.g., change in the microenvironment, release therapeutics, etc.) and then initiate/modulate a desired biofunction. Here, magnetic-responsive carboxylated multi-walled carbon nanotubes (cMWCNTs) are integrated into 3D collagen/polylactic acid (PLA) scaffold via a reproducible filtration-based method. The integrity and biomechanical performance of the collagen/PLA scaffolds are preserved after cMWCNT integration. In vitro safety assessment of cMWCNT/collagen/PLA scaffolds shows neither cytotoxicity effects nor macrophage pro-inflammatory response, supporting further in vitro studies. The cMWCNT/collagen/PLA scaffolds enhance chondrocytes metabolic activity while maintaining high cell viability and extracellular matrix (i.e., type II collagen and aggrecan) production. Comprehensive in vitro study applying static and pulsed magnetic field on seeded scaffolds shows no specific cell response in dependence with the applied field. This result is independent of the presence or absence of cMWCNT into the collagen/PLA scaffolds. Taken together, these findings provide additional evidence of the benefits to exploit the CNTs outstanding properties in the design of stimuli-responsive scaffolds.publishedVersio

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

A follow-up study of first episode major depressive disorder. Impairment in inhibition and semantic fluency—potential predictors for relapse?

The present study investigated the Executive Functions (EF) of inhibition, mental flexibility and phonemic and semantic fluency in a 1-year follow-up assessment of patients diagnosed with first episode Major Depressive Disorder (MDD). In the acute phase, the patient group performed significantly poorer compared to the control group (CG) in inhibition and semantic fluency. The present study pursued these findings from the acute phase to see if the impairment seen in inhibition and semantic fluency in the acute phase normalized or persisted in the follow-up assessment. In addition, the present study investigated the association between poor inhibition and semantic fluency performance and the experience of relapse during the 1-year period. Twenty eight patients and 28 individually matched control subjects were included. EF was reassessed using three tests from the Delis Kaplan Executive Function System (D-KEFS). Results : There was a significant decrease in depression severity score from the acute phase, showing that most of the patients were in remission in the follow-up assessment. Results showed a sustained impairment in inhibition and semantic fluency in the patient group. However, the performance in inhibition was more severe when an additional requirement of mental flexibility was included. There were no group differences in the other EF functions measured. Further, patients with a relapse in the course of 1 year performed significantly poorer in inhibition/switching at inclusion compared to patients that did not relapse and the CG. This relationship was not found for semantic fluency. Poor performance in inhibition and semantic fluency are prolonged despite symptom reduction in patients with a first episode of MDD. Moreover, although based on a small sample of patients, the present study showed that there may be a relationship between impaired ability in the EF of inhibition/switching and vulnerability for the experience of relapse

Executive Functioning in recurrent - and first episode Major Depressive Disorder: Longitudinal studies

Major Depressive Disorder (MDD) is in the acute phase of illness often associated with neuropsychological impairment in a range of cognitive domains such as attention, memory, psychomotor speed and Executive Functioning (EF). However, the literature is inconclusive regarding the pattern of cognitive impairment in MDD and if these functions are state or trait dependent. MDD is one of the most common psychiatric disorders and is characterized by a high relapse risk. However, the factors affecting the vulnerability for relapse are still not well understood. his thesis is based on three papers that investigated EF in MDD, both in the acute phase of illness and in phases of symptom reduction and remission. The first paper investigated EF in a group of patients with recurrent unipolar MDD. The second and third paper investigated EF in a group of first- episode unipolar MDD patients. In all three papers, EF was investigated using neuropsychological tests from the Delis-Kaplan Executive Function System (D-KEFS). Paper I investigated EF in a group of recurrent unipolar MDD patients in a follow- up study. More specifically, the paper addressed the question if the impairment in the specific EF functions of inhibition and semantic fluency seen in the acute phase of illness would persist or be normalized with symptom reduction in a 9 month follow -up study. The results showed that the patient group was still impaired in inhibition, inhibition/switching and semantic fluency compared to the control group, despite significant symptom reduction. Performance in mental flexibility in general and phonemic fluency was equal to the control subjects. There were no association between depressive symptoms and EF impairment. The results further showed that the same patients that were impaired in inhibition in the acute phase of illness were still impaired at the follow- up assessment. Thus, seen in a 9 month perspective, the results indicate that inhibition may represent a stable trait characterizing patients with recurrent MDD. Paper II investigated EF in a group of first episode unipolar MDD patients in the acute phase of illness. More specifically, the paper addressed the question if the EF impairment that was found in the recurrent patient group also was evident in a group of first episode MDD patients. Inhibition, mental flexibility, phonemic- and semantic fluency, planning- and problem solving were investigated. The results showed that the patient group was impaired in the EF functions of inhibition, inhibition/switching and semantic fluency compared to the control group. The patient group did not show impairment in the other EF measures that were assessed, such as mental flexibility in general, phonemic fluency, planning and problem-solving. Furthermore, the patient group was impaired compared to the control group in three measures of processing speed. However, the results indicated that poor processing speed could not account for the poor EF performance. There was further no association between severity of depression and EF impairment. The results from paper II show that inhibition and semantic fluency are impaired in first episode MDD. Paper III investigated EF in a group of first episode unipolar MDD patients in a follow-up study. More specifically, the paper addressed the question if the impairment in inhibition and semantic fluency seen in the acute phase persisted or normalized in a longitudinal perspective of one year. In addition the third paper investigated if there was a relationship between poor inhibition and semantic fluency and the experience of relapse during the follow-up period. The EF of inhibition, mental flexibility, phonemic and semantic fluency was reinvestigated. Mean scores showed that the patients were in remission at the follow-up assessment. The results showed that the patient group still performed poorer in inhibition, inhibition/switching, semantic fluency and some measures of processing speed compared to the control group. Poor processing speed could however not solely account for the impaired performance in EF. In addition, the results showed that the performance in inhibition were more impaired when an additional requirement of mental flexibility was demanded. The performance in inhibition/switching at inclusion was further found to be more impaired in patients that experienced a relapse during the follow- up period, and found to enhance the likelihood of experiencing relapse. However, due to smallsample size and other possible confounding variables that could affecting the association found between tendency to relapse and poor performance in inhibition/switching in paper III, these results should be viewed as preliminary and thus be interpreted with caution. Taken together, the present thesis demonstrates that inhibition and semantic fluency are impaired in patients with MDD across the course of the disorder, and thus may represent stable, enduring cognitive traits in MDD independent of symptom severity. Further, the present thesis indicates that impaired inhibition with the additional requirement of mental flexibility may represent a vulnerability factor for the experience of relapse

A follow-up study of first episode major depressive disorder. Impairment in inhibition and semantic fluency – potential predictors for relapse?

The present study investigated the Executive Functions (EF) of inhibition, mental flexibility and phonemic and semantic fluency in a one-year follow-up assessment of patients diagnosed with first episode Major Depressive Disorder (MDD). In the acute phase, the patient group performed significantly poorer compared to the control group in inhibition and semantic fluency. The present study pursued these findings from the acute phase to see if the impairment seen in inhibition and semantic fluency in the acute phase normalized or persisted in the follow-up assessment. In addition, the present study investigated the association between poor inhibition and semantic fluency performance and the experience of relapse during the one-year period. Twenty eight patients and 28 individually matched control subjects were included. EF was reassessed using three tests from the Delis Kaplan Executive Function System (D-KEFS). Results: There was a significant decrease in depression severity score from the acute phase, showing that most of the patients were in remission in the follow-up assessment. Results showed a sustained impairment in inhibition and semantic fluency in the patient group. However, the performance in inhibition was more severe when an additional requirement of mental flexibility was included. There were no group differences in the other EF functions measured. Further, patients with a relapse in the course of one year performed significantly poorer in inhibition/switching at inclusion compared to patients that did not relapse and the control group. This relationship was not found for semantic fluency. Poor performance in inhibition and semantic fluency are prolonged despite symptom reduction in patients with a first episode of MDD. Moreover, although based on a small sample of patients, the present study showed that there may be a relationship between impaired ability in the EF of inhibition/switching and vulnerability for the experience of relapse