The importance of examining early maladaptive schemas in the diagnosis and treatment of obsessive-compulsive disorder.

Introduction: The aim of the study was twofolded: to identify the early maladaptive schemas characteristic of obsessive-compulsive disorder in a Hungarian sample and, to examine the presence and severity of comorbid anxiety and depressive symptoms in the light of early maladaptive schemas. Methods: 112 participants (58 men and 54 women) diagnosed with OCD were involved in the study. The questionnaire package consisted of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), the Penn State Worry Questionnaire (PSWQ) and the Schema Questionnaire (SQ). Results: We identified five early maladaptive schemas with a direct effect on the manifestation of obsessive-compulsive symptoms: Mistrust-Abuse, Inferiority/Shame, Dependence/Incompetence, Insufficient Self-Control/Self-Discipline and Entitlement/Grandiosity (reversed effect). Based on the severity of the early maladaptive schemas, three significantly different groups could be identified in our sample: patients with mild, moderate and high schema-values. Among the groups significant differences can be found in the appearance and severity of compulsive symptoms, as well as in the presence of anxiety and depressive symptoms. But contrary to our expectations, not the severity, but the numberof the early maladaptive schemas showed a stronger correlation with the symptom variables. An additional result of our study derives from canonical correlation, addressing the relationship among early maladaptive schemas, OCD symptoms, anxiety and depressive symptoms from a new perspective. The results highlight that OCD is only one and not the most serious consequence of personality damage, indicated by early maladaptive schemas. Discussion: The results of our study suggest that obsessive-compulsive disorder can be divided into several subgroups, which can be separated in terms of symptom severity, comorbid psychiatric symptoms and personality impairment patterns. The relationship between OCD symptom severity and personality impairment seems to be not directly proportional. Our results strengthen the new dimensional view of OCD, which can determine the selection of the appropriate therapeutic treatment method beyond the diagnostic process.

[Personalized treatment options for spinal muscular atrophy]. / A spinalis izomatrophia személyre szabott terápiás lehetoségei.

Spinal muscular atrophy (SMA) is an autosomal recessive disease leading to progressive muscle weakness and atrophy, in severe cases also affecting the bulbar and respiratory muscles.The clinical spectrum of the disease is extremely variable, in the most severe cases resulting in perinatal death, while at the least severe end of the spectrum causing some motor deficits in old age without the loss of ambulation. Spinal muscular atrophy care has changed dramatically in recent years due to the availability of new therapeutic options. 
The FDA approved nusinersen in 2016, this was followed by the approval of onasemnogene abeparvovec in 2019 and risdiplam in 2020. The EMA approved all three therapies a year later. Two of the threapies work at the pre-mRNA level, one at the DNA level. The clinical studies leading to the approval of the three drugs included patients of different ages and clinical conditions, and utilised partly different motor and functional scales. Therefore, direct comparison of these clinical studies is not possible. However, an increasing amount of real-world data contribute to the better understanding of the efficacy of the different therapies for patients of different ages and clinical conditions, in a real-world setting. Thus, the question may arise “Which is the best SMA therapy?”. This is an impossible question to answer. Indeed the question “Which therapy is the most suitable for a certain patient at a certain time?” is much more realistic. Here, we provide a brief overview of the objectively measurable results of the three therapies to date and an outlook into future therapeutic avenues. 

Childhood traumatization and dissociative experiences among maladaptive and normal daydreamers in a Hungarian sample.

The aim of the study was to identify some potential etiological segments of maladaptive daydreaming, especially the relationships between maladaptive daydreaming, childhood traumatization, and dissociative propensity. The questionnaire package included the Hungarian version of the Maladaptive Daydreaming Scale, the Traumatic Antecedents Questionnaire, as well as the Dissociation Questionnaire. 717 participants were recruited online, 106 of whom were problematic daydreamers. The results revealed that certain types of childhood trauma occurred significantly more frequently in the group of maladaptive daydreamers. Furthermore, maladaptive daydreamers possessed a significantly higher level of dissociative propensity compared to normal daydreamers. The estimated SEM models showed that dissociative experiences - more precisely Identity confusion and fragmentation and Lack of control - mediated the relationship between certain childhood traumatic experiences and maladaptive daydreaming. The results suggest that we should consider childhood traumatization and increased dissociative propensity as potentially significant factors in the etiology of maladaptive daydreaming.

Pathological personality traits of maladaptive daydreamers measured by the Personality Inventory for DSM-5 in a psychiatric sample.

This study aimed to estimate the frequency of maladaptive daydreaming and to explore the pathological personality traits of probable maladaptive daydreamers. Our sample consisted of 239 psychiatric patients. After screening, 42 persons were probable maladaptive, while 197 participants prove to be normal daydreamers. Two pathological domains and three facets measured by the Personality Inventory for DSM-5 showed a moderate significant correlation with the Maladaptive Daydreaming Scale. The score of nearly every domain and facet was slightly higher among probable maladaptive daydreamers. To quantify the difference between the groups, effect sizes were calculated: Significant difference was found on the domain level in Antagonism, while on the facet level in Hostility, Grandiosity, Attention Seeking, Unusual Beliefs and Experiences, Cognitive and Perceptual Dysregulation. The group of probable maladaptive daydreamers was further examined to identify potential subgroups. Cluster analysis revealed heterogeneity in the severeness and patterns of pathological personality domains. Cluster 1 showed higher mean scores on the PID domains and on the MDS compared to Cluster 2. Clusters 1 and 2 broke further down into two subclusters: Cluster 1a and Cluster 1b differed in their mean scores on the domains of Antagonism and Detachment; the mean scores of Cluster 2a were uniformly low on each domain, while the mean values of Cluster 2b were scattered in a mixed way on the domains. Our results suggest that maladaptive daydreaming might manifest with differently pathological personality profiles in the background. This aspect might worth considering in planning treatment.

Phase 1 and preclinical profiling of ESM-HDAC391, a myeloid-targeted histone deacetylase inhibitor, shows enhanced pharmacology and monocytopaenia.

AIMS: To improve the tolerability and therapeutic application of histone deacetylase inhibitors (HDACi), by application of an esterase-sensitive motif (ESM), to target pharmacological activity directly to mononuclear myeloid cells expressing the processing enzyme carboxylesterase-1 (CES1). METHODS: This first-in-human study comprised single and multiple ascending dose cohorts to determine safety and tolerability. Pharmacodynamic parameters included acetylation, cytokine inhibition and intracellular concentrations of processed acid metabolite in isolated monocytes. Mechanistic work was conducted in vitro and in a CES1/Es1elo mouse strain. RESULTS: ESM-HDAC391 showed transient systemic exposure (plasma half-life of 21-30 min) but selective retention of processed acid for at least 12 hours, resulting in robust targeted mechanistic engagement (increased acetylation in monocytes plus inhibition of ex vivo stimulated cytokine production). ESM-HDAC391 was well tolerated and clinical toxicities common to non-targeted HDACi were not observed. ESM-HDAC391 treatment was accompanied by the novel finding of a dose-dependent monocyte depletion that was transient and reversible and which plateaued at 0.06 × 109 monocytes/L after repeat dosing with 20 or 40 mg. Characterisation of monocyte depletion in transgenic mice (CES1/Es1elo ) suggested that colony stimulating factor 1 receptor loss on circulating cells contributed to ESM-HDAC-mediated depletion. Further mechanistic investigations using human monocytes in vitro demonstrated HDACi-mediated change in myeloid fate through modulation of colony stimulating factor 1 receptor and downstream effects on cell differentiation. CONCLUSION: These findings demonstrate selective targeting of monocytes in humans using the ESM approach and identify monocytopaenia as a novel outcome of ESM-HDACi treatment, with implications for potential benefit of these molecules in myeloid-driven diseases.

Design, Synthesis, and Characterization of I-BET567, a Pan-Bromodomain and Extra Terminal (BET) Bromodomain Oral Candidate.

Through regulation of the epigenome, the bromodomain and extra terminal (BET) family of proteins represent important therapeutic targets for the treatment of human disease. Through mimicking the endogenous N-acetyl-lysine group and disrupting the protein-protein interaction between histone tails and the bromodomain, several small molecule pan-BET inhibitors have progressed to oncology clinical trials. This work describes the medicinal chemistry strategy and execution to deliver an orally bioavailable tetrahydroquinoline (THQ) pan-BET candidate. Critical to the success of this endeavor was a potency agnostic analysis of a data set of 1999 THQ BET inhibitors within the GSK collection which enabled identification of appropriate lipophilicity space to deliver compounds with a higher probability of desired oral candidate quality properties. SAR knowledge was leveraged via Free-Wilson analysis within this design space to identify a small group of targets which ultimately delivered I-BET567 (27), a pan-BET candidate inhibitor that demonstrated efficacy in mouse models of oncology and inflammation.

Physical-Chemical Aspects of the Preparation and Drug Release of Electrospun Scaffolds.

Fibers were spun from a mixture of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) solution of poly(lactic acid)(PLA) containing various amounts of amoxicillin (Amox) as the active component. Composition changes during spinning, structure, solubility, and the location of the drug were considered during the evaluation of drug release and microbial activity. The results showed that the composition of the material changes during the preparation procedure. The solubility of the drug in the components and that of the components in each other is limited, which results in the formation of several phases and the precipitation of the drug. The technology used results in the partitioning of the drug; some is located inside, while the rest is among the fibers. The wetting of the fibers or disks by the water-based dissolution media is poor, the penetration of the liquid into and the diffusion of the active component out of the device takes considerable time. Drug release takes place in one, burst-like step, only Amox located among the fibers dissolve and diffuse into the surrounding medium. The slow second stage of release claimed in the literature is less probable because the size of the Amox molecule is considerably larger than the holes creating the free volume of the polymer. The prepared device has antimicrobial activity, inhibits the growth of the two bacterial strains studied. The time scale of activity is short and corresponds to that of the release experiments and the burst-like behavior of the device. The results clearly prove that physical-chemical factors play a determining role in the effect and efficiency of medical devices prepared from electrospun fibers containing an active component.

The Role of Micronutrients to Support Immunity for COVID-19 Prevention.

The World Health Organization declared the novel coronavirus, named as SARS-CoV-2, as a global pandemic in early 2020 after the disease spread to more than 180 countries leading to tens of thousands of cases and many deaths within a couple of months. Consequently, this paper aims to summarize the evidence for the relationships between nutrition and the boosting of the immune system in the fight against the disease caused by SARS-CoV-2. This review, in particular, assesses the impact of vitamin and mineral supplements on the body's defence mechanisms against SARS-CoV-2. The results revealed that there is a strong relationship between the ingestion of biological ingredients like vitamins C-E, and minerals such as zinc, and a reduction in the effects of coronavirus infection. These can be received from either nutrition rich food sources or from vitamin supplements. Furthermore, these macromolecules might have roles to play in boosting the immune response, in the healing process and the recovery time. Hence, we recommend that eating healthy foods rich in vitamins C-E with zinc and flavonoids could boost the immune system and consequently protect the body from serious infections.

Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features.

BACKGROUND: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. METHODS: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. RESULTS: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. CONCLUSIONS: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.

[The importance of patient reported outcome measures in Pompe disease]. / A betegek által riportált kimeneti mutatók jelentosége Pompe-kórban.

BACKGROUND AND PURPOSE: In recent decades it has become increasingly important to involve patients in their diagnostic and treatment process to improve treatment outcomes and optimize compliance. By their involvement, patients can become active participants in therapeutic developments and their observations can be utilized in determining the unmet needs and priorities in clinical research. This is especially true in rare diseases such as Pompe disease. Pompe disease is a genetically determined lysosomal storage disease featuring severe limb-girdle and axial muscle weakness accompanied with respiratory insufficiency, in which enzyme replacement therapy (ERT) now has been available for 15 years. METHODS: In our present study, patient reported outcome measures (PROMs) for individuals affected with Pompe disease were developed which included questionnaires assessing general quality of life (EuroQoL, EQ-5D, SF36), daily activities and motor performance (Fatigue Severity Score, R-PAct-Scale, Rotterdam and Bartel disability scale). Data were collected for three subsequent years. The PROM questionnaires were a good complement to the physician-recorded condition assessment, and on certain aspects only PROMs provided information (e.g. fatigue in excess of patients' objective muscle weakness; deteriorating social activities despite stagnant physical abilities; significant individual differences in certain domains). The psychological effects of disease burden were also reflected in PROMs. RESULTS: In addition to medical examination and certain endpoints monitored by physicians, patient perspectives need to be taken into account when assessing the effectiveness of new, innovative treatments. With involvement of patients, information can be obtained that might remain uncovered during regular medical visits, although it is essential in determining the directions and priorities of clinical research. CONCLUSION: For all orphan medicines we emphasize to include patients in a compulsory manner to obtain general and disease-specific multidimensional outcome measures and use them as a quality indicator to monitor treatment effectiveness.

[Consensus statement of the Hungarian Clinical Neurogenic Society about the therapy of adult SMA patients]. / A Magyar Klinikai Neurogenetikai Társaság konszenzusajánlása a felnottkori spinalis izomatrophia (SMA) kezeléséhez.

BACKGROUND AND PURPOSE: Background - Spinal muscular atrophy (SMA) is an autosomal recessive, progressive neuromuscular disorder resulting in a loss of lower motoneurons. Recently, new disease-modifying treatments (two drugs for splicing modification of SMN2 and one for SMN1 gene replacement) have become available. Purpose - The new drugs change the progression of SMA with neonatal and childhood onset. Increasing amount of data are available about the effects of these drugs in adult patients with SMA. In this article, we summarize the available data of new SMA therapies in adult patients. METHODS: Methods - Members of the Executive Committee of the Hungarian Clinical Neurogenetic Society surveyed the literature for palliative treatments, randomized controlled trials, and retrospective and prospective studies using disease modifying therapies in adult patients with SMA. Patients - We evaluated the outcomes of studies focused on treatments of adult patients mainly with SMA II and III. RESULTS: In this paper, we present our consensus statement in nine points covering palliative care, technical, medical and safety considerations, patient selection, and long-term monitoring of adult patients with SMA. CONCLUSION: This consensus statement aims to support the most efficient management of adult patients with SMA, and provides information about treatment efficacy and safety to be considered during personalized therapy. It also highlights open questions needed to be answered in future. Using this recommendation in clinical practice can result in optimization of therapy.

Inhibition of ABCG2/BCRP-mediated transport-correlation analysis of various expression systems and probe substrates.

BCRP / ABCG2 is a key determinant of pharmacokinetics of substrate drugs. Several BCRP substrates and inhibitors are of low passive permeability, and the vesicular transport assay works well in this permeability space. Membranes were prepared from BCRP-HEK293, MCF-7/MX, and baculovirus-infected Sf9 cells with (BCRP-Sf9-HAM), and without (BCRP-Sf9) cholesterol loading. Km values for three substrates - estrone-3-sulfate, sulfasalazine, topotecan - correlated well between the four expression systems. In contrast, a 10-20-fold range in Vmax values was observed, with BCRP-HEK293 membranes possessing the largest dynamic range. IC50 values of the different test systems were similar to each other, with 94.4% of pairwise comparisons being within 3-fold. Substrate dependent inhibition showed somewhat greater variation, as 81.4% of IC50 values in the BCRP-HEK293 membranes were within 3-fold in pairwise comparisons. Overall, BCRP-HEK293 membranes demonstrated the highest activity. The IC50 values showed good concordance but substrate dependent inhibition was observed for some drugs.

Psychometric properties of the Maladaptive Daydreaming Scale in a sample of Hungarian daydreaming-prone individuals.

OBJECTIVES: The aim of the study is to adapt the Maladaptive Daydreaming Scale (MDS-16) to Hungarian, assess its psychometric properties, and establish its cut-off score. In addition, the relationship between maladaptive daydreaming and adverse childhood experiences was examined. METHOD: Study participants were recruited online via snowball sampling. Based on three inclusion criteria (self-identified MDer status; control over daydreaming; frequency of daydreaming) 160 out of 494 respondents were included in the study. RESULTS: Our results confirm both the high reliability and convergent validity of the questionnaire. The cut-off score of 60 percentiles can reliably discriminate between excessive and normal daydreamers. The general applicability of the MDS-16-HU was tested and confirmed by the use of the Adverse Childhood Experience Questionnaire (ACE-10), a short, self-report questionnaire. Its results showed that certain types of childhood adversities increase the likelihood of maladaptive daydreaming. CONCLUSIONS: The instrument is a valid and reliable measure, therefore it can serve as a useful screening tool in clinical practice. In addition, our findings highlighted the role of childhood adversities in the aetiology of maladaptive daydreaming.

[Pompe disease treated with enzyme replacement therapy in pregnancy]. / Tapasztalataink Pompe-betegségben terhesség alatt alkalmazott enzimpótló kezeléssel és az irodalom áttekintése.

Pompe disease is a rare lysosomal storage disease inherited in a recessive manner resulting muscular dystrophy. Due to the lack of the enzyme alpha glucosidase, glycogen accumulates in the cells. In the infantile form of Pompe disease hypotonia and severe cardio-respiratory failure are common leading to death within 2 years if left untreated, while the late-onset form is characterized with limb-girdle and axial muscle weakness accompanied with respiratory dysfunction. Pompe disease has been treated with regular intake of the missing enzyme since 2006, which significantly improved the survival and severity of symptoms in patients of both subtypes. The enzyme replacement therapy (ERT) is safe and well tolerated. However, limited data are available on its use in pregnancy. Our goal is to share our experience and review the literature on the safety of enzyme replacement therapy for Pompe disease during pregnancy and post partum.

Single-Cell Elasticity Measurement with an Optically Actuated Microrobot.

A cell elasticity measurement method is introduced that uses polymer microtools actuated by holographic optical tweezers. The microtools were prepared with two-photon polymerization. Their shape enables the approach of the cells in any lateral direction. In the presented case, endothelial cells grown on vertical polymer walls were probed by the tools in a lateral direction. The use of specially shaped microtools prevents the target cells from photodamage that may arise during optical trapping. The position of the tools was recorded simply with video microscopy and analyzed with image processing methods. We critically compare the resulting Young's modulus values to those in the literature obtained by other methods. The application of optical tweezers extends the force range available for cell indentations measurements down to the fN regime. Our approach demonstrates a feasible alternative to the usual vertical indentation experiments.

Etiology-related Degree of Sprouting of Parvalbumin-immunoreactive Axons in the Human Dentate Gyrus in Temporal Lobe Epilepsy.

In the present study, we examined parvalbumin-immunoreactive cells and axons in the dentate gyrus of surgically resected tissues of therapy-resistant temporal lobe epilepsy (TLE) patients with different etiologies. Based on MRI results, five groups of patients were formed: (1) hippocampal sclerosis (HS), (2) malformation of cortical development, (3) malformation of cortical development + HS, (4) tumor-induced TLE, (5) patients with negative MRI result. Four control samples were also included in the study. Parvalbumin-immunoreactive cells were observed mostly in subgranular location in the dentate hilus in controls, in tumor-induced TLE, in malformation of cortical development and in MR-negative cases. In patients with HS, significant decrease in the number of hilar parvalbumin-immunoreactive cells and large numbers of ectopic parvalbumin-containing neurons were detected in the dentate gyrus' molecular layer. The ratio of ectopic/normally-located cells was significantly higher in HS than in other TLE groups. In patients with HS, robust sprouting of parvalbumin-immunoreactive axons were frequently visible in the molecular layer. The extent of sprouting was significantly higher in TLE patients with HS than in other groups. Strong sprouting of parvalbumin-immunoreactive axons were frequently observed in patients who had childhood febrile seizure. Significant correlation was found between the level of sprouting of axons and the ratio of ectopic/normally-located parvalbumin-containing cells. Electron microscopy demonstrated that sprouted parvalbumin-immunoreactive axons terminate on proximal and distal dendritic shafts as well as on dendritic spines of granule cells. Our results indicate alteration of target profile of parvalbumin-immunoreactive neurons in HS that contributes to the known synaptic remodeling in TLE.

Nephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domains.

This study demonstrates a role for the extracellular matrix protein nephronectin (NPNT) in promoting experimental breast cancer brain metastasis, possibly through enhanced binding to- and migration through brain endothelial cells. With the introduction of more targeted breast cancer treatments, a prolonged survival has resulted during the last decade. Consequently, an increased number of patients develop metastasis in the brain, a challenging organ to treat. We recently reported that NPNT was highly expressed in primary breast cancer and associated with unfavourable prognosis. The current study addresses our hypothesis that NPNT promotes brain metastases through its integrin-binding motifs. SAGE-sequencing revealed that NPNT was significantly up-regulated in human breast cancer tissue compared to pair-matched normal breast tissue. Human brain metastatic breast cancers expressed both NPNT and its receptor, integrin α8ß1. Using an open access repository; BreastMark, we found a correlation between high NPNT mRNA levels and poor prognosis for patients with the luminal B subtype. The 66cl4 mouse cell line was used for expression of wild-type and mutant NPNT, which is unable to bind α8ß1. Using an in vivo model of brain metastatic colonization, 66cl4-NPNT cells showed an increased ability to form metastatic lesions compared to cells with mutant NPNT, possibly through reduced endothelial adhesion and transmigration.

Application of Atypical Acetyl-lysine Methyl Mimetics in the Development of Selective Inhibitors of the Bromodomain-Containing Protein 7 (BRD7)/Bromodomain-Containing Protein 9 (BRD9) Bromodomains.

Non-BET bromodomain-containing proteins have become attractive targets for the development of novel therapeutics targeting epigenetic pathways. To help facilitate the target validation of this class of proteins, structurally diverse small-molecule ligands and methodologies to produce selective inhibitors in a predictable fashion are in high demand. Herein, we report the development and application of atypical acetyl-lysine (KAc) methyl mimetics to take advantage of the differential stability of conserved water molecules in the bromodomain binding site. Discovery of the n-butyl group as an atypical KAc methyl mimetic allowed generation of 31 (GSK6776) as a soluble, permeable, and selective BRD7/9 inhibitor from a pyridazinone template. The n-butyl group was then used to enhance the bromodomain selectivity of an existing BRD9 inhibitor and to transform pan-bromodomain inhibitors into BRD7/9 selective compounds. Finally, a solvent-exposed vector was defined from the pyridazinone template to enable bifunctional molecule synthesis, and affinity enrichment chemoproteomic experiments were used to confirm several of the endogenous protein partners of BRD7 and BRD9, which form part of the chromatin remodeling PBAF and BAF complexes, respectively.

[Investigation of sleep and fatigue in patients with cancer]. / Az alvás és a kimerültség vizsgálata daganatos betegek körében.

INTRODUCTION: The diagnosis of cancer elicits greater distress than any other diagnosis. The prevalence of psychological difficulties is high in cancer, and resources of the medical staff are limited. The development of efficient screening measures is therefore of utmost importance. Sleep is vital to all psychological functioning and poor sleep is a known problem in cancer. AIM: The main goal of the present study was testing of visual analogue scales assessing sleep quality and fatigue. METHOD: Sleep quality and fatigue were assessed with visual analogue scales. The Sleep Condition Indicator, the Athens Insomnia Scale and the Cancer Fatigue Scale were also included. Psychological distress was assessed with the Generalized Anxiety Disorder Scale, the Beck Depression Inventory and the Brief Difficulties in Emotion Regulation Scale. Pain and well-being was measured with the Faces of Pain Scale and the WHO Well-being Scale, respectively. A total of 71 patients with cancer were enrolled in this study. RESULTS: Insomnia and fatigue - measuring them with visual and several-item scales - showed high correlation with the measures of distress (anxiety, depression, emotion regulation difficulties) and pain. Distress and pain showed significant negative correlation with well-being. CONCLUSIONS: It has been affirmed that sleep quality is crucial in the changes of distress, pain and general well-being in cancer patients. It affirms that the visual analogue scales assessing sleep quality and fatigue - besides sleep quality and fatigue - are acceptable screening tools of distress and decreased well-being. Their use in clinical practice is recommended for screening in cancer patients and providing indications for onco-psychological treatment. Orv Hetil. 2018; 159(42): 1720-1726.

Third-generation Sequencing Reveals Extensive Polycistronism and Transcriptional Overlapping in a Baculovirus.

The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is an insect-pathogen baculovirus. In this study, we applied the Oxford Nanopore Technologies platform for the analysis of the polyadenylated fraction of the viral transcriptome using both cDNA and direct RNA sequencing methods. We identified and annotated altogether 132 novel transcripts and transcript isoforms, including 4 coding and 4 non-coding RNA molecules, 47 length variants, 5 splice isoforms, as well as 23 polycistronic and 49 complex transcripts. All of the identified novel protein-coding genes were 5'-truncated forms of longer host genes. In this work, we demonstrated that in the case of transcript start site isoforms, the promoters and the initiator sequence of the longer and shorter variants belong to the same kinetic class. Long-read sequencing also revealed a complex meshwork of transcriptional overlaps, the function of which needs to be clarified. Additionally, we developed bioinformatics methods to improve the transcript annotation and to eliminate the non-specific transcription reads generated by template switching and false priming.