Introduction: The topic of work-life harmony of Child Protection Authority (OSPOD) workers is crucial, not only for their personal well-being, but also for the long-term sustainability of this demanding profession. This article focuses on developing a deeper understanding of the strategies that workers use to maintain work-life harmony, and provides insights into the role of organizational support in this process. Methods: The research was conducted through interpretive phenomenological analysis (IPA) and qualitative semi-structured interviews. Results: The results show that employees use a variety of individual strategies such as self-development, mindset, networking, time management and personal space for relaxation. They perceive support from the organization mainly through supervision, flexible working hours, professional training, and employee benefits. An interesting finding was that workers did not pay attention to the development of spiritual needs, which are an important aspect of wellbeing. Conclusion: The study highlights the importance of systematic organizational support in the field of work-life harmony and recommends measures that can contribute to the development of wellbeing of workers and their sustainability in the profession.

• MeSH
• Adaptation, Psychological MeSH
• Humans MeSH
• Organization and Administration MeSH
• Resilience, Psychological MeSH
• Work-Life Balance * classification   methods   MeSH
• Interviews as Topic MeSH
• Child Welfare psychology   MeSH
• Social Workers * psychology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Nedd4-2 E3 ligase regulates Na+ homeostasis by ubiquitinating various channels and membrane transporters, including the epithelial sodium channel ENaC. In turn, Nedd4-2 dysregulation leads to various conditions, including electrolytic imbalance, respiratory distress, hypertension, and kidney diseases. However, Nedd4-2 regulation remains mostly unclear. The present study aims at elucidating Nedd4-2 regulation by structurally characterizing Nedd4-2 and its complexes using several biophysical techniques. Our cryo-EM reconstruction shows that the C2 domain blocks the E2-binding surface of the HECT domain. This blockage, ubiquitin-binding exosite masking by the WW1 domain, catalytic C922 blockage and HECT domain stabilization provide the structural basis for Nedd4-2 autoinhibition. Furthermore, Ca2+-dependent C2 membrane binding disrupts C2/HECT interactions, but not Ca2+ alone, whereas 14-3-3 protein binds to a flexible region of Nedd4-2 containing the WW2 and WW3 domains, thereby inhibiting its catalytic activity and membrane binding. Overall, our data provide key mechanistic insights into Nedd4-2 regulation toward fostering the development of strategies targeting Nedd4-2 function.

• MeSH
• Cryoelectron Microscopy MeSH
• HEK293 Cells MeSH
• Humans MeSH
• Models, Molecular MeSH
• Protein Domains MeSH
• 14-3-3 Proteins * metabolism   chemistry   MeSH
• Ubiquitination MeSH
• Nedd4 Ubiquitin Protein Ligases * metabolism   chemistry   genetics   ultrastructure   MeSH
• Calcium * metabolism   MeSH
• Protein Binding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Ecto-5'-nucleotidase (CD73) is a novel target in cancer (immuno)therapy. Its blockade prevents the formation of immunosuppressive and cancer-promoting adenosine from AMP. Here, we report on the development of a series of small molecules that mimic adenine nucleotides, in which the ribose moiety was replaced by an alkyl chain. Its length was found to be crucial for potency. A crystal structure of the N6-disubstituted acyclic ADP analog 26 (N6-benzyl,N6-methyladenine-9-yl)pentyloxydiphosphonate) in complex with human CD73 revealed that the flexible pentyl linker adopts to interdomain rotation angles differing by up to 18.5°. The most potent CD73 inhibitor of the present series was analog 27 (N6-benzyl,N6-methyladenine-9-yl)hexyloxydiphosphonate, PSB-24000) which exhibited submicromolar potency at human CD73 (Ki 563 nM at soluble CD73; Ki 481 nM at membrane-bound CD73 of triple-negative breast cancer cells). Acyclic nucleotide analogs may be advantageous compared to the previously reported nucleotidic CD73 inhibitors due to their high chemical stability, and because less off-target effects are to be expected. The structure-activity relationships discovered in this study provide valuable insights which will be useful for the development of CD73 inhibitors as immunotherapeutic drugs.

• MeSH
• 5'-Nucleotidase * antagonists & inhibitors   metabolism   MeSH
• Cisplatin chemistry   pharmacology   MeSH
• GPI-Linked Proteins antagonists & inhibitors   metabolism   MeSH
• Enzyme Inhibitors * pharmacology   chemistry   chemical synthesis   MeSH
• Humans MeSH
• Models, Molecular MeSH
• Molecular Structure MeSH
• Purine Nucleotides * chemistry   pharmacology   chemical synthesis   MeSH
• Pyrimidine Nucleotides * chemistry   pharmacology   chemical synthesis   MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: To identify the current challenges and barriers within the esports environment in the Central and East European countries and to explore the potential for collaboration between universities, particularly sports faculties, and the esports ecosystem. The research also aims to clarify the perceived roles of universities, including their research domains, within the context of esports. METHODS: The research is based on a qualitative approach. Semi-structured interviews were used in the qualitative research to analyze attitudes toward the esports issues. The interviews were conducted with 18 stakeholders, the recordings were transcribed verbatim, coded and analyzed using the MAXQDA Analytics Pro software. RESULTS: The analysis led to the following findings: Universities can collaborate with esports teams, players, and other stakeholders to research and analyze players' physical state and performance, offering courses and certifications for coaches and managers of esports teams, where they would learn gaming skills and player's health and physical preparation. Moreover, universities can facilitate interaction between esports teams and experts in the field of nutrition, sleep, etc., potentially leading to improved health and performance of players. Finally, universities can collaborate with esports associations to establish standards and licensing requirements for coaches, managers, and other professionals in the esports industry. CONCLUSION: The paper advocates collaboration between universities and esports organizations and encourages flexibility and innovation. Recommendations include establishing formalized training programs for players, coaches, managers and organizers, promoting esports within the university environment, fostering positive perceptions, and supporting university leagues.

• Publication type
• Journal Article MeSH

AIM: To determine whether people with type 1 diabetes (T1D) initiating glucose sensor monitoring experience greater improvements in HbA1c when provided with education on carbohydrate counting and flexible insulin dosing than those who do not receive nutrition education. MATERIALS AND METHODS: Our retrospective observational study included 329 people with T1D initiating glucose sensor monitoring between 2015 and 2021. The participants were divided into two groups: one group attended at least one structured educational session with a registered dietitian (n = 126), while the other group did not receive structured education (n = 203). After 12 months of glucose sensor initiation, we compared glycaemic outcomes and CGM metrics between the two groups. RESULTS: At glucose sensor initiation, both groups with and without education had similar HbA1c levels (7.64% [60.0 mmol/mol] vs. 7.66% [60.2 mmol/mol]). After twelve months, the education group demonstrated greater improvement in glycemic outcomes (HbA1c 7.17% [54.9mmol/mol] vs. 7.37% [57.1 mmol/mol], p < 0.05) and spent significantly more time in the target range than did the group without structured education (68.8% vs. 64.1%, p < 0.05). We observed an inverse correlation between the number of completed educational sessions and HbA1c after 12 months, as well as between the number of educational sessions and the change in HbA1c. CONCLUSIONS: People with T1D who initiated glucose sensor monitoring alongside nutrition education showed greater improvements in HbA1c and increased time spent in the target glucose range compared to individuals who did not receive structured education. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT06264271.

• MeSH
• Diabetes Mellitus, Type 1 * blood   MeSH
• Adult MeSH
• Glycated Hemoglobin * analysis   metabolism   MeSH
• Hypoglycemic Agents administration & dosage   MeSH
• Insulin administration & dosage   MeSH
• Blood Glucose * analysis   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Glycemic Control MeSH
• Retrospective Studies MeSH
• Blood Glucose Self-Monitoring * MeSH
• Patient Education as Topic * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

Routine outcome monitoring (ROM) has become an increasingly utilized tool in therapeutic practice that has the potential to improve therapy outcomes. This study aimed to synthesize the findings of existing qualitative studies investigating how clinicians use ROM in their work with clients. A systematic search of qualitative studies on clinicians' experience with the use of ROM in mental health services was conducted via PsycInfo, PsycArticles, Medline, Web of Science, and Scopus databases. Qualitative meta-analysis was used to synthesize the finding of the primary studies. Forty-seven studies met the inclusion criteria. The analysis resulted in 21 meta-categories organized into six clusters, namely (1) obtaining clinically relevant information, (2) adapting treatment, (3) facilitating communication, (4) enhancing the therapeutic relationship, (5) facilitating change in clients, and (6) personalized usage of ROM. The meta-analysis revealed that clinicians utilized ROM in diverse ways, including both informational and communicational functions. From the clinicians' perspective, ROM was an element that, on the one hand, introduced additional structure and standardization in treatment and, on the other hand, allowed for greater flexibility and tailoring of treatment.

• MeSH
• Mental Disorders therapy   MeSH
• Outcome Assessment, Health Care MeSH
• Communication MeSH
• Qualitative Research MeSH
• Humans MeSH
• Attitude of Health Personnel MeSH
• Psychotherapists * MeSH
• Psychotherapy * organization & administration   standards   MeSH
• Mental Health Services organization & administration   standards   MeSH
• Professional-Patient Relations MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH

OBJECTIVE: The clinical diversity of schizophrenia is reflected by structural brain variability. It remains unclear how this variability manifests across different gray and white matter features. In this meta- and mega-analysis, the authors investigated how brain heterogeneity in schizophrenia is distributed across multimodal structural indicators. METHODS: The authors used the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6,037 individuals for a given brain measure. Variability and mean values of cortical thickness, cortical surface area, cortical folding index, subcortical volume, and fractional anisotropy were examined in individuals with schizophrenia and healthy control subjects. RESULTS: Individuals with schizophrenia showed greater variability in cortical thickness, cortical surface area, subcortical volume, and fractional anisotropy within the frontotemporal and subcortical network. This increased structural variability was mainly associated with psychopathological symptom domains, and the schizophrenia group frequently displayed lower mean values in the respective structural measures. Unexpectedly, folding patterns were more uniform in individuals with schizophrenia, particularly in the right caudal anterior cingulate region. The mean folding values of the right caudal anterior cingulate region did not differ between the schizophrenia and healthy control groups, and folding patterns in this region were not associated with disease-related parameters. CONCLUSIONS: In patients with schizophrenia, uniform folding patterns in the right caudal anterior cingulate region contrasted with the multimodal variability in the frontotemporal and subcortical network. While variability in the frontotemporal and subcortical network was associated with disease-related diversity, uniform folding may indicate a less flexible interplay between genetic and environmental factors during neurodevelopment.

• MeSH
• Anisotropy MeSH
• White Matter pathology   diagnostic imaging   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain * pathology   diagnostic imaging   MeSH
• Schizophrenia * pathology   diagnostic imaging   MeSH
• Gray Matter pathology   diagnostic imaging   MeSH
• Diffusion Tensor Imaging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH

PSMA-617 is recognized as a benchmark ligand for prostate-specific membrane antigen (PSMA) owing to its broad utilization in prostate cancer (PCa) targeted radionuclide therapy. In this study, the structure-activity relationships (SAR) of PSMA-617 and two novel analogs featuring modified linkers were investigated. In compounds P17 and P18, the 2-naphthyl-l-Ala moiety was replaced with a less lipophilic 3-styryl-l-Ala moiety while the cyclohexyl ring in P18 was replaced with a phenyl group. The first ever crystal structure of the PSMA/PSMA-617 complex reported here revealed a folded conformation of the PSMA-617 linker while for the PSMA/P17 and PSMA/P18 complexes, the extended orientations of the linkers revealed linker flexibility within the PSMA cavity, a change in binding that can be exploited for the structure-guided design of PSMA-targeting agents. Despite structural differences from PSMA-617, the analogs maintained high PSMA inhibition potency, cellular binding, and internalization. In vivo biodistribution studies revealed comparable tumor uptake across all three compounds with P18 displaying higher spleen accumulation, likely due to phenyl ring lipophilicity. These SAR findings provide a strategic framework for the rational design of PSMA ligands, paving the way for the development of next-generation theranostic agents for PCa.

• Publication type
• Journal Article MeSH

MicroRNAs (miRNAs) are small non-coding RNAs (18-22 nucleotides) that regulate gene expression and are associated with various diseases, including Laryngeal Cancer (LCa), which has a high mortality rate due to late diagnosis. Traditional methods for miRNA detection present several drawbacks (time-consuming steps, high cost and high false positive rate). Early-stage diagnosis and selective detection of miRNAs remain challenging. This study proposes a 3D flexible biosensor that combines nanofibers (NFs), gold nanoparticles (AuNPs), and an inverse molecular sentinel (iMS) for enzyme-free, SERS-based detection of miRNA-223-3p, evaluated as a potential LCa biomarker. The electrospun flexible nanofibers decorated with AuNPs enhance Raman signal. Selective detection of miRNA-223-3p is achieved by immobilizing an iMS-DNA probe labeled with a Raman reporter (Cyanine 3) on the AuNPs. The iMS distinctive stem-and-loop structure undergoes a conformational change upon interaction with the miRNA-223-3p, producing an "on to off" SERS signal. The proposed sensor demonstrated a linear detection range from 10 to 250 fM, with a limit of detection (LOD) of 19.50 ± 0.05 fM. The sensor selectivity was confirmed by analyzing the SERS signal behaviour in the presence of both Non-complementary miRNA and miRNA with three mismatched base pairs. This easily fabricable sensor requires no amplification and offers key advantages, including sensitivity, flexibility, and cost-effectiveness.

• MeSH
• Biosensing Techniques * methods   MeSH
• Early Detection of Cancer methods   MeSH
• Metal Nanoparticles * chemistry   MeSH
• Humans MeSH
• Limit of Detection MeSH
• MicroRNAs * analysis   genetics   MeSH
• Laryngeal Neoplasms * diagnosis   genetics   MeSH
• Nanofibers * chemistry   MeSH
• Spectrum Analysis, Raman * methods   MeSH
• Gold * chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

An active and constructive process whereby individuals possess the ability to develop, implement, and flexibly maintain planned behavior in order to achieve a desired achievement goal is referred to as self-regulation. The aim of the present study is to examine the factorial structure and psychometric properties of the Self-Regulation Questionnaire, validated in the Czech educational context (SRQ-CZ). The other target is to identify any usage of self-regulation strategies which may differ as nationality, gender, age, education, and internal motivation to learn come into play. A total of 1,711 adult learners from Poland, Serbia, Slovakia, and the Czech Republic who were enrolled in a formal secondary or higher education system pursuing professions in the field of humanities, social and health care sciences participated in this study. A measurement-invariant four-factor model was obtained across all countries (min. CFI, TLI = 0.918, and 0.902, max. RMSEA = 0.059; ω between 0.625 and 0.838, and Cronbach's α between 0.622 and 0.837), including the Impulse Control, Goal Orientation, Self-Direction, and Decision Making subscales. Generally, the study confirmed a gradual increase in scores that measure positive self-regulatory qualities (Goal Orientation and Decision Making) and a decrease in unfavorable self-regulatory qualities (Impulse Control and Self-Direction) with higher age, education, and motivation, with no gender differences reported within countries. Moreover, scores on Goal Orientation and Decision Making dominated between countries. In conclusion, the SRQ-CZ demonstrated its suitability for cross-national comparisons, and personal characteristics appear to be important factors that distinguish those with high and low self-regulation.

• Publication type
• Journal Article MeSH