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Aims/hypothesis: This study aimed to describe the relationship between breastfeeding episodes and maternal glucose levels, and to assess whether this differs with closed-loop vs open-loop (sensor-augmented pump) insulin therapy., Methods: Infant-feeding diaries were collected at 6 weeks, 12 weeks and 24 weeks postpartum in a trial of postpartum closed-loop use in 18 women with type 1 diabetes. Continuous glucose monitoring (CGM) data were used to identify maternal glucose patterns within the 3 h of breastfeeding episodes. Generalised mixed models adjusted for breastfeeding episodes in the same woman, repeat breastfeeding episodes, carbohydrate intake, infant age at time of feeding and early pregnancy HbA 1c . This was a secondary analysis of data collected during a randomised trial (ClinicalTrials.gov registration no. NCT04420728)., Results: CGM glucose remained above 3.9 mmol/l in the 3 h post-breastfeeding for 93% (397/427) of breastfeeding episodes. There was an overall decrease in glucose at nighttime within 3 h of breastfeeding (1.1 mmol l -1 h -1 decrease on average; p=0.009). A decrease in nighttime glucose was observed with open-loop therapy (1.2 ± 0.5 mmol/l) but was blunted with closed-loop therapy (0.4 ± 0.3 mmol/l; p<0.01, open-loop vs closed-loop)., Conclusions/interpretation: There is a small decrease in glucose after nighttime breastfeeding that usually does not result in maternal hypoglycaemia; this appears to be blunted with the use of closed-loop therapy., (© 2024. The Author(s).)

Objectives: Closed-loop insulin delivery has the potential to offer women with type 1 diabetes a break from intense diabetes self-care efforts postpartum. Our aim in this study was to explore the views and opinions of hybrid closed-loop users and their partners in the first 24 weeks postpartum., Methods: This qualitative study was embedded in a controlled study of women with type 1 diabetes randomized to closed-loop insulin delivery (MiniMed™ 670G or 770G) or sensor-augmented pump use for 1 to 11 weeks 6 days postpartum, with all on closed-loop delivery from 12 to 24 weeks postpartum. Semistructured interviews were conducted with 16 study participants and their partners at 12 and 24 weeks postpartum. Thematic analyses were used to examine participants' and partners' experiences., Results: Participants' positive perceptions of closed-loop use related to reduced hypoglycemia, in contrast to previous experiences with nonautomated insulin delivery. These perceptions were balanced against frustrations with the system, allowing blood glucose levels to be higher than desired. Closed-loop use did not influence infant feeding choice, but infant feeding and care impacted participants' diabetes management. Partners expressed uncertainty about the closed loop taking away control from participants who were highly skilled with diabetes self-management., Conclusions: Participants reported that closed-loop insulin delivery resulted in less time spent in hypoglycemia when compared with the previously used nonautomated delivery. Yet, participants desired a greater understanding of the workings of the closed-loop algorithm. Our study provides potential users with realistic expectations about the experience with the MiniMed 670G or 770G closed-loop system in the postpartum period., (Copyright © 2024 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

For most diseases and disorders occurring in the brain, the full causes behind them are yet unknown, but many show signs of dysfunction of amino acid transporters or abnormalities in amino acid metabolism. The blood-brain barrier (BBB) plays a key role in supporting the function of the central nervous system (CNS). Because of its unique structure, the BBB can maintain the optimal environment for CNS by controlling the passage of hydrophilic molecules from blood to the brain. Nutrients, such as amino acids, can cross the BBB via specific transporters. Many amino acids are essential for CNS function, and dysfunction of these amino acid transporters can lead to abnormalities in amino acid levels. This has been linked to causes behind certain genetic brain diseases, such as schizophrenia, autism spectrum disorder, and Huntington's disease (HD). One example of crucial amino acids is L-Cys, the rate-limiting factor in the biosynthesis of an important antioxidant, glutathione (GSH). Deficiency of L-Cys and GSH has been linked to oxidative stress and has been shown as a plausible cause behind certain CNS diseases, like schizophrenia and HD. This review presents the current status of potential L-Cys therapies and gives future directions that can be taken to improve amino acid transportation related to distinct CNS diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aimed to compare the effects of a mobile health intervention based on social cognitive theory with standard care on maximal mouth opening, exercise compliance, and self-efficacy in patients receiving proton and heavy ion therapy for head and neck cancer., Methods: This open-label, parallel-group, randomized, superiority trial involved a self-developed "Health Enjoy System" intervention. We assessed maximal mouth opening, exercise compliance, and self-efficacy at baseline (T 0 ), post-treatment (T 1 ), and at 1 month (T 2 ) and 3 months (T 3 ) after radiotherapy. Generalized estimating equations were used to analyze differences between the groups over time, with results reported as P values and 95% confidence intervals (CIs)., Results: The study included 44 participants. At T 3 , the intervention group showed a 6 mm greater increase in maximal interincisal opening than the control group (mean difference = 6.0, 95% CI = 2.4 to 9.5, P = 0.001). There was also a significant difference in exercise compliance between the groups (mean difference = 31.7, 95% CI = 4.6 to 58.8, P = 0.022). However, no significant difference in self-efficacy was found between the groups., Conclusion: This study demonstrated that an mHealth intervention incorporating behavior change theory could effectively enhance or maintain maximal mouth opening in patients undergoing proton and heavy ion therapy for head and neck cancer in China. This approach provides valuable support during and after treatment., Trial Registration: ChiCTR: ChiCTR2300067550. Registered 11 Jan 2023., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs) 1 , which influences offspring development and adult phenotypes 1-7 . Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood 8 . Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization., (© 2024. The Author(s).)

Purpose: To identify and synthesise interactive digital tools used to support the empowerment of people with cancer and the outcomes of these tools., Methods: A systematic literature review was conducted using PubMed, CINAHL, Web of Science, Cochrane, Eric, Scopus, and PsycINFO databases in May 2023. Inclusion criteria were patient empowerment as an outcome supported by interactive digital tools expressed in study goal, methods or results, peer-reviewed studies published since 2010 in cancer care. Narrative synthesis was applied, and the quality of the studies was assessed following Joanna Briggs Institute checklists., Results: Out of 1571 records screened, 39 studies published in 2011-2022 with RCT (17), single-arm trial (15), quasi-experimental (1), and qualitative designs (6) were included. A total of 30 interactive digital tools were identified to support empowerment (4) and related aspects, such as self-management (2), coping (4), patient activation (9), and self-efficacy (19). Significant positive effects were found on empowerment (1), self-management (1), coping (1), patient activation (2), and self-efficacy (10). Patient experiences were positive. Interactivity occurred with the tool itself (22), peers (7), or nurses (7), physicians (2), psychologists, (2) or social workers (1)., Conclusion: Interactive digital tools have been developed extensively in recent years, varying in terms of content and methodology, favouring feasibility and pilot designs. In all of the tools, people with cancer are either active or recipients of information. The research evidence indicates positive outcomes for patient empowerment through interactive digital tools. Thus, even though promising, there still is need for further testing of the tools., (© 2024. The Author(s).)

Objectives: The aim of this integrative review is to identify, describe, and synthesise evidence regarding students' perceptions of online degree programmes in nurse education, their academic performance, and the factors associated with their academic performance., Design: Integrative review., Data Sources: Four databases, CINAHL, ERIC (Ebsco), PubMed/MEDLINE, and Web of Science were searched. The reference lists of included studies were reviewed to identify other relevant studies., Review Methods: Whittemore and Knafl's method was used as a guideline for the integrative review. Peer-reviewed studies describing students' perceptions of-or academic performance in-online degree programmes in nurse education were included in the review without time limitations. The quality of the selected article was assessed using the Mixed Method Appraisal Tool., Results: Nursing students' perceptions of online degree programmes were categorised into enabling career development, content delivered online, and community belonging. Factors related to student's academic performance were associated with individual students and the characteristics of online learning environments. Factors associated with students' academic performance were individual self-direction, formal communication skills, and working and educational backgrounds. Factors associated with academic performance in an online learning environment were categorised into regular feedback and methods for learning., Conclusions: Online degree programmes in nurse education contribute to developing pedagogy through a satisfactory work-life balance, students' experiences of community and support, pleasant digital content, and various teaching methods by faculties. The study findings of this review have implications for educators to develop and adopt strategies for advancing digital environments with the pedagogy that supports community building to meet the needs of individual students., Competing Interests: Declaration of competing interest The authors state there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Nurse educators need a high level of professional competence to educate future health care professionals. Professional competence supports occupational well-being whilst high mental workload can undermine it. There is little existing research into nurse educators' professional competence, occupational well-being, mental workload, and the relationships between them, particularly in the European context., Objectives: To describe the professional competence, personal occupational well-being, and mental workload of nurse educators in four European countries, and to explore how the professional competence and mental workload of nurse educators relate to their personal occupational well-being., Design: Cross-sectional study design with quantitative survey data., Setting: Nurse educators from Finland, Spain, Slovakia, and Malta., Methods: The data were collected from 302 nurse educators through an online questionnaire which used the Health and Social Care Educator's Competence (HeSoEduCo) instrument. This contains 43 items which measure areas of professional competence. Statistical analysis involved descriptive and multivariate analysis., Results: Nurse educators self-assessed their overall professional competence as high. Competence in evidence-based practice was assessed as the highest whilst cultural competence was perceived to be the lowest of the six competence areas. Nurse educators perceived their levels of personal occupational well-being and the balance of mental workload as moderate. However, these levels varied between the four countries. Professional competence, more specifically administrative and curriculum competence, and a balanced mental workload were positively related to personal occupational well-being., Conclusions: The educators who perceive themselves to have very good professional competence and a balanced mental workload are more likely to report high occupational well-being. The findings suggest that nurse educators' cultural competence needs to be strengthened and intervention research is needed to determine ways of reducing mental workload and increasing the occupational well-being of nurse educators., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To analyze methodological approaches (theoretical frameworks, study designs, methods) and competence areas of nursing students in research on virtual reality simulations (VRS) with a high level of immersion., Methods: A scoping review was performed. A systematic search of the literature was conducted on MEDLINE, CINAHL and ERIC databases on 30/11/22. In addition, a manual search was utilized. The extracted data relating to the research questions was descriptively analyzed and results were narratively summarized., Results: In total 23 studies were included in the review. Selected studies employed a wide range of theoretical frameworks and research designs. The studies aimed to develop competences both through complex interventions where team-based skills are required in acute situations, and they described basic nursing interventions where individual skills are required in non-acute nursing care., Conclusions: A significant amount of the selected studies did not utilize a learning theory or an instructional design framework as a basis for their research. More knowledge was found on training specific skills compared to facilitating the attitudes and values of the participants. Therefore, there is a need for further research on whether nursing students' attitudes and values can be supported through VRS with a high level of immersion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: High body weight is a protective factor against osteoporosis, but obesity also suppresses bone metabolism and whole-body insulin sensitivity. However, the impact of body weight and regular training on bone marrow (BM) glucose metabolism is unclear. We studied the effects of regular exercise training on bone and BM metabolism in monozygotic twin pairs discordant for body weight., Methods: We recruited 12 monozygotic twin pairs (mean ± SD age 40.4 ± 4.5 years; body mass index 32.9 ± 7.6, mean difference between co-twins 7.6 kg/m 2 ; eight female pairs). Ten pairs completed the 6-month long training intervention. We measured lumbar vertebral and femoral BM insulin-stimulated glucose uptake (GU) using 18 F-FDG positron emission tomography, lumbar spine bone mineral density and bone turnover markers., Results: At baseline, heavier co-twins had higher lumbar vertebral BM GU (p < .001) and lower bone turnover markers (all p < .01) compared with leaner co-twins but there was no significant difference in femoral BM GU, or bone mineral density. Training improved whole-body insulin sensitivity, aerobic capacity (both p < .05) and femoral BM GU (p = .008). The training response in lumbar vertebral BM GU was different between the groups (time × group, p = .02), as GU tended to decrease in heavier co-twins (p = .06) while there was no change in leaner co-twins., Conclusions: In this study, regular exercise training increases femoral BM GU regardless of weight and genetics. Interestingly, lumbar vertebral BM GU is higher in participants with higher body weight, and training counteracts this effect in heavier co-twins even without reduction in weight. These data suggest that BM metabolism is altered by physical activity., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Patient stress is often overlooked in the care of patients with neurological problems. Nursing theorists have previously heralded stress assessment through conceptual clarification, while clinical nurses in the health care system hold an ideal position for implementation of assessment and coordination of support. Integrated with a hospital assessment and support scheme, recognition of stress as a target of systematic assessment can lead to improved clinical outcomes., Objective: The aim of the study was to describe and compare patient-reported outcome measures suitable for assessment of the stress response as symptoms in neurological patients., Design: This study is an integrative review and concept development of patient stress based on qualitative and quantitative analysis of available self-reporting instruments., Methods: Instruments were retreived with a systematic search from PubMed, CINAHL, PsychINFO and Web of Science reference databases on August 2, 2021. Search terms associated with the concept of stress symptoms were used. Instrument inclusion was done with the guidance of authoritative symptom inventories, with partial confirmation by a second author to mitigate bias. In the analysis, the instruments included in the review were quantitatively described and compared. Insights from the instrument composition led to clarification of our concept of stress response to further refine the list of instruments suitable for self-assessment of the stress status. This study was not registered., Results: Based on the inclusion criteria, 23 patient-reported outcome measures extending over a variety of stress concepts were included. The similarity of items among the instruments implied a symptom cluster delineated by 59 common symptom subclasses that were grouped together in a re-classification of instrument items. A comparative quantitative analysis prompted us to distinguish the concept of stress response from antecedent, consequent, and related concepts as a manifestation of mental, somatic, and behavioral domains. Ten instruments with items covering the three domains, each with unique qualities regarding number of items, measured spread, and letter count were described., Conclusions: Within an organizational framework, effective allotment among types of support can be founded on the patient's stress status and the stressors. The stress status manifests itself as a set of measurable symptoms. Optimal instruments for use in systematic clinical assessment of neurological patients' stress status should satisfy the suggested specification of the stress response with a minimal number of items and concise wording. Finding and including the relevant instruments for analysis were the main limitation of the study., Tweetable Abstract: Stress of neurological patients needs to be assessed and addressed. We ranked 10 suitable instruments that can be useful in the assessment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Purpose: Feedback from service users is a valuable source for improving the quality of care and services, potentially reflecting the successes and failures in providing empowering healthcare. In supporting empowerment, the multidimensionality of knowledge of service users is assumed to be a crucial factor, yet feedback has not been explored from the perspective of empowering knowledge. In this study, the aim was to analyze the knowledge areas expressed in the service users' feedback from the point of view of empowering knowledge., Patients and Methods: This was a retrospective study utilizing systematically collected service-user feedback from a feedback register of one university hospital district in Finland. Free-form feedback (n = 26,374) along with structured evaluative feedback was given by the patients themselves or their significant others, either by text message or using a feedback form, in 2019. The content of the feedback was analyzed according to the empowering knowledge areas (biophysiological, cognitive, functional, experiential, ethical, social, and financial), quantified, and analyzed statistically in relation to the background characteristics of service users., Results: Service users gave multidimensional free-form feedback about the knowledge and educational practices in care and services. In the free-form feedback, the most common empowering knowledge areas were biophysiological and cognitive ones, whilst experiential, ethical, social, and financial areas were the least common. The highest ratings of structured evaluative feedback were associated with the cognitive and ethical areas., Conclusion: Register-based feedback is systematic data for quality evaluation. In this study, service users seem to actively evaluate the knowledge procession in care and services, and therefore, they can be actors involved in developing the quality of educational practices. It does, however, indicate a need to add multidimensionality and improve the quality of the knowledge, and by that, advance the potential of empowerment among diverse service users., Competing Interests: Dr Helena Leino-Kilpi reports grants from Turku University Hospital, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2023 Richards et al.)

Objective: This study aimed to evaluate the efficacy of closed-loop insulin delivery postpartum., Research Design and Methods: In this open-label, randomized controlled trial, postpartum individuals with type 1 diabetes were randomized to hybrid closed-loop insulin delivery with the MiniMed 670G/770G system in automode or sensor-augmented pump therapy in the first 12-weeks postpartum followed by a continuation phase with closed-loop insulin delivery for all until 24 weeks postpartum., Results: Eighteen participants (mean ± SD age 32 ± 3.5 years, diabetes duration 22 ± 7.3 years, and early pregnancy HbA1c 52 ± 6.8 mmol/mol [6.9 ± 0.9%]) completed 24 weeks of postpartum follow-up. In the randomized phase, percent time in range 70-180 mg/dL (3.9-10 mmol/L) did not differ between groups (79.2 ± 8.7% vs. 78.2 ± 6.0%; P = 0.41). Participants randomized to closed-loop insulin delivery spent less time <70 mg/dL (3.9 mmol/L) and <54 mg/dL (3.0 mmol/L) (1.7 ± 0.8% vs. 5.5 ± 3.3% [P < 0.001] and 0.3 ± 0.2% vs. 1.1 ± 0.9% [P = 0.008]). Time >180 mg/dL (10 mmol/L) was not different between groups (18.7 ± 8.8% vs. 15.9 ± 7.7%; P = 0.21). In the continuation phase, those initially randomized to sensor-augmented pump therapy had less time <70 mg/dL after initiation of closed-loop insulin delivery (5.5 ± 3.3% vs. 3.3 ± 2.2%; P = 0.039). The closed-loop group maintained similar glycemic metrics in both study phases. There were no episodes of diabetic ketoacidosis or severe hypoglycemia in the randomized or continuation phase in either group., Conclusions: Women randomized to closed-loop insulin delivery postpartum had less hypoglycemia than those randomized to sensor-augmented pump therapy. There were no safety concerns. These findings are reassuring for use of closed-loop insulin delivery postpartum because of its potential to reduce hypoglycemia., (© 2023 by the American Diabetes Association.)

Objectives: Little is known about the epidemiology and healthcare burden of pediatric intestinal failure (IF). We aimed to assess the incidence, prevalence, healthcare resource utilization (HCRU), and related costs of pediatric short bowel syndrome (SBS) using follow-up data from the largest hospital district in Finland., Methods: This retrospective registry study utilized electronic healthcare data covering all pediatric patients with SBS-IF born between 2010 and 2019 at the Hospital District of Helsinki and Uusimaa in Finland. Patients were followed from birth until the end of 2020 and compared to control patients, all from the same hospital system., Results: In total, 38 patients with SBS-IF and 1:5 matched controls were included, with median follow-up time of almost 6 years from birth. Over half of the patients were born early preterm (gestational age ≤30 weeks). The incidence of pediatric SBS-IF was 24 per 100,000 live births. The HCRU was higher compared to controls and most of the inpatient days incurred during the first year of the SBS-IF patients' life. The average hospital-based HCRU costs were €221,000 for the first year and €57,000 for whole follow-up annually. The costs were higher for the early preterm patients and accumulated mainly from inpatient days., Conclusions: SBS-IF is a rare disease with a relatively low number of patients treated at each hospital district. The burden on the hospital system, as well as the patient's family, is especially high at the onset as the newborns with SBS-IF spend a significant part of their first year of life in the hospital., (Copyright © 2023 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims and Objectives: To analyse research-based evidence about patients' right to know from their own perspective to promote ethically high-quality nursing and to identify future research areas., Background: Patients' right to know is a fundamental right. Although of topical research interest, the current state of scientific evidence on patients' right to know has not been reviewed., Design: A scoping review according to the methodological framework by Arksey & O'Malley and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews., Methods: In June 2022, a literature search was conducted in the Ovid Medline, CINAHL and Cochrane Library databases. The inclusion criteria were peer-reviewed, empirical studies on the right to know with samples comprising adult patients. Data were analysed with inductive content analysis, and methodological quality was assessed with Mixed Methods Appraisal Tool., Results: Out of 2658 identified reports, 12 were selected for analysis. Based on the results, the research on patients' right to know can be classified into two main content categories: (1) expectations of the right and (2) realisation of the right. In the quality assessment, most of the reports did not meet all the quality criteria, the most common deficits being related to instrumentation and risk of bias., Conclusions: Research-based evidence on patients' right to know provided a general insight into expectations and realisation of the right to know and not to know. The results indicate a need for continued efforts for novel approaches with high-quality methodological choices in future studies., Relevance to Clinical Practice: Nurses make constantly ethical decisions: The findings of this study can be useful for their decision-making and understanding of the patient's perspective on knowledge issues, and therefore, support ethically high-quality patient education., Patient or Public Contribution: No direct patient or public contribution to the review., (© 2022 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Purpose: Electronic (e) patient-reported outcomes (PROs) have been shown to improve the quality of life and survival in chemotherapy treated advanced cancer patients. We hypothesized that multidimensional ePRO centered approach could improve symptom management, streamline patient flow, and optimize the use of healthcare resources., Methods: In this multicenter trial (NCT04081558), colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy as adjuvant or in the first- or second-line setting in advanced disease were included in the prospective ePRO cohort, while a comparative retrospective cohort was collected from the same institutes. The investigated tool consisted of a weekly e-symptom questionnaire integrated to an urgency algorithm and laboratory value interface, which generated semi-automated decision support for chemotherapy cycle prescription and individualized symptom management., Results: Recruitment to the ePRO cohort occurred 1/2019-1/2021 (n = 43). The comparator group (n = 194) consisted of patients treated in the same institutes 1-7/2017. The analysis was limited to adjuvant treated (n = 36 and n = 35). The feasibility of the ePRO follow-up was good with 98% reporting easy usage and 86% improved care, while health care personnel valued the easy use and logical workflow. In the ePRO cohort, 42% needed a phone call before planned chemotherapy cycles, while this was 100% in the retrospective cohort (p = 1.4e-8). Peripheral sensory neuropathy was detected significantly earlier with ePRO followed (p = 1e-5) but did not translate to earlier dose reduction, delays, or unplanned therapy termination compared to the retrospective cohort., Conclusion: The results suggest that the investigated approach is feasible and streamlines workflow. Earlier symptom detection may improve the quality in cancer care., (© 2023. The Author(s).)

Aim: This review aimed to identify validated self-reported instruments used to measure nurses' competence or attribute(s) of competence in empowering patient education, to describe their development and main content and critically appraise and summarize the quality of the instruments., Design: Systematic review., Data Sources: Electronic databases of PubMed, CINAHL and ERIC were searched from January 2000 to May 2022., Review Methods: Data was extracted following predetermined inclusion criteria. With the support of the research group, two researchers performed data selection and appraised the methodological quality using the COnsensus-based Standards for the selection of health status Measurement INstruments checklist (COSMIN)., Results: A total of 19 studies reporting 11 instruments were included. The instruments measured varied attributes of competence and the contents were heterogenous reflecting the complex nature of both empowerment and competence as concepts. Overall, the reported psychometric properties of the instruments and methodological quality of the studies were at least adequate. However, there was variation in the testing of the instruments' psychometric properties and lack of evidence limited the evaluation of both the methodological quality of the studies and quality of instruments., Conclusion: The psychometric properties of the existing instruments assessing nurses' competence in empowering patient education need to be tested further, and future instrument development should be built on a clearer definition of empowerment as well as on more rigorous testing and reporting. In addition, continued efforts to clarify and define both empowerment and competence on the conceptual level are needed., Impact: Evidence on nurses' competence in empowering patient education and its valid and reliable assessment instruments is scarce. Existing instruments are heterogenous and are often missing proper testing of validity and reliability. These findings contribute to further research on developing and testing the instruments of competence in empowering patient education and strengthening nurses' empowering patient education competence in the clinical practice., (© 2023 John Wiley & Sons Ltd.)

Aim: This study aimed to describe the psychosocial support healthcare professionals in specialist palliative inpatient units provide to family members of palliative care patients., Design: A qualitative descriptive design., Method: The data were collected with focus group interviews and analysed with inductive content analysis., Results: Altogether, 48 healthcare professionals, including physicians, registered nurses and practical nurses, participated in the study. Information sharing was recognised as an essential element of support. Methods to improve support of family members included an opportunity to allocate recourses to the families, systematic support and strengthening healthcare professionals' competence in family care. The healthcare professionals describe their perceptions of psychosocial support for family members primarily through patient care and the patient's situation rather than family needs. Direct support for the family members is realised principally by information sharing and conversations. Healthcare professionals express their opportunities to implement support focusing on family members' needs restricted by reason of organisational resources. The information can be used when developing and improving family care in palliative care context to recognise the most relevant needs from healthcare professionals' perspective and also when implementing healthcare professionals' education and training., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Aim: The aim of this review was to synthesize the instruments that assess nurse educators' competence., Design: A scoping review was conducted with the five-stage process informed by Arksey and O'Malley., Review Methods: The predetermined search strategy was used including an additional hand search. The studies were selected according to inclusion and exclusion criteria to answer the research questions followed: (1) "What instruments are used to assess nurse educators' competence?", (2) "How are the psychometric properties of nurse educators' competence instruments reported in the literature?". The thematic synthesis was used., Data Sources: The literature search was conducted in January 2021 using the CINAHL, MEDLINE and ERIC databases from January 2000 to December 2020., Results: Of the 1,567 articles searched through, 25 met the inclusion criteria. A total of 19 instruments with 10 areas of competence were identified. Typical competence areas were pedagogical and nursing competence. In addition, leadership in managerial competence was included in several instruments. However, the theoretical backgrounds of the instruments varied and the psychometric properties were reported in varied ways in reviewed studies., Implications for the Profession: This study provides evidence about the valid and comprehensive assessment of nurse educators' competence, as competent nurse educators promote excellence in nursing education. To assess a nurse educators' competence comprehensively, a variety of theoretical backgrounds of this competence and more than one instrument for the measurement need to be considered. The selection of the instruments to assess nurse educators' competence should be based on the selected theoretical background and use of valid measurements., Reporting Method: This study was reported by following the reporting recommendations of the PRISMA extension for Scoping Reviews (PRISMA-ScR)., Patient or Public Contribution: No Patient or Public Contribution was applied, since research design was a scoping review., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Purpose: Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally. Therefore, it is important to know whether MOR expression in BAT shows seasonal variation., Methods: We determined the effect of photoperiod on BAT MOR availability using [ 11 C]carfentanil positron emission tomography (PET). Adult rats (n = 9) were repeatedly imaged under various photoperiods in order to simulate seasonal changes., Results: Long photoperiod was associated with low MOR expression in BAT (β =  - 0.04, 95% confidence interval: - 0.07, - 0.01), but not in muscles. We confirmed the expression of MOR in BAT and muscle using immunofluorescence staining., Conclusion: Photoperiod affects MOR availability in BAT. Sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. The present study supports the utility of [ 11 C]carfentanil PET to study the peripheral MOR system., (© 2022. The Author(s).)

Objective: In vivo corneal confocal microscopy (CCM) is a novel, rapid, and non-invasive technique that identifies early small fiber damage and can predict the progression and development of clinical neuropathy in adults with type 1 diabetes. However, its usefulness in children is not well established. This study compared corneal confocal microscopy with neuropathic symptoms, signs, and objective measures of neuropathy for the diagnosis of diabetic neuropathy in children with type 1 diabetes., Research Design and Methods: A total of 83 children with type 1 diabetes and 83 healthy participants of similar age underwent assessment of neuropathy symptoms, signs, nerve conduction studies, quantitative sensory and autonomic function testing, and in vivo CCM., Results: Only of 3/83 (4%) children with type 1 diabetes had subclinical neuropathy. However, corneal nerve fiber density (p = 0.001), branch density (p = 0.006), fiber length (p = 0.002), tibial motor nerve amplitude and conduction velocity, and sural sensory nerve amplitude and conduction velocity (all p < 0.004) were lower in participants with type 1 diabetes than in the controls. Vibration, cooling, and warm perception thresholds and deep breathing heart rate variability were not found to be different (all p > 0.05) between children with type 1 diabetes and healthy controls. Multivariate regression analysis identified a possible association between body mass index and decreased corneal nerves., Conclusions: Decreased corneal nerves and abnormal nerve conduction were found in children with type 1 diabetes. CCM may allow rapid objective detection of subclinical diabetic neuropathy in children and adolescents with type 1 diabetes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Radiolabeled peptides have emerged as highly specific agents for targeting receptors expressed in tumors for therapeutic and diagnostic purposes. Peptides developed for positron emission tomography (PET) are typically radiolabeled using prosthetic groups or bifunctional chelators for fast "kit-like" incorporation of the radionuclide into the structure. A novel [ 18 F]alkylammoniomethyltrifluoroborate ([ 18 F]AmBF 3 ) tetrazine (Tz), [ 18 F]AmBF 3 -Tz, was developed for the [ 18 F]fluorination of trans -cyclooctene (TCO)-modified biomolecules using Tyr 3 -octreotides (TOCs) as model peptides. [ 18 F]AmBF 3 -Tz (A m = 15.4 ± 9.2 GBq/μmol, n = 14) was evaluated in healthy mice by ex vivo biodistribution and PET/computed tomography (CT), where the radiolabel in the prosthetic group was found stable in vivo , indicated by the low bone uptake in tibia (0.4 ± 0.1% ID/g, t = 270 min). TCO-TOCs tailored with polyethylene glycol (PEG) linkers were radiolabeled with [ 18 F]AmBF 3 -Tz, forming two new tracers, [ 18 F]AmBF 3 -PEG 4 -TOC (A m = 2.8 ± 1.8 GBq/μmol, n = 3) and [ 18 F]AmBF 3 -PEG 7 -TOC (A m of 6.0 ± 3.4 GBq/μmol, n = 13), which were evaluated by cell uptake studies and ex vivo biodistribution in subcutaneous AR42J rat pancreatic carcinoma tumor-bearing nude mice. The tracer demonstrating superior behavior ex vivo , the [ 18 F]AmBF 3 -PEG 7 -TOC, was further evaluated with PET/CT, where the tracer provided clear tumor visualization (SUV baseline = 1.01 ± 0.07, vs SUV blocked = 0.76 ± 0.04) at 25 min post injection. The novel AmBF 3 -Tz demonstrated that it offers potential as a prosthetic group for rapid radiolabeling of biomolecules in mild conditions using bioorthogonal chemistry.

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule, which supports contact between leukocytes and inflamed endothelium. There is evidence that VAP-1 is involved in the recruitment of leukocytes to melanoma tumors. Interleukin-2 (IL-2)-based immunotherapy is an efficient therapy that promotes immune system activity against cancers but is associated with toxicity. In the present study, we evaluated the feasibility of PET/CT imaging using the radiotracer [ 68 Ga]Ga-DOTA-Siglec-9, which is targeted to VAP-1, to monitor pharmacodynamic effects of a novel FAP-IL2v immunocytokine (a genetically engineered variant of IL-2 fused with fibroblast activation protein) in the B16-FAP melanoma model. At 9 days after the inoculation of B16-FAP melanoma cells, mice were studied with [ 68 Ga]Ga-DOTA-Siglec-9 PET/CT as a baseline measurement. Immediately after baseline imaging, mice were treated with FAP-IL2v or vehicle, and treatment was repeated 3 days later. Subsequent PET/CT imaging was performed 3, 5, and 7 days after baseline imaging. In addition to in vivo PET imaging, ex vivo autoradiography, histology, and immunofluorescence staining were performed on excised tumors. B16-FAP tumors were clearly detected with [ 68 Ga]Ga-DOTA-Siglec-9 PET/CT during the follow-up period, without differences in tumor volume between FAP-IL2v-treated and vehicle-treated groups. Tumor-to-muscle uptake of [ 68 Ga]Ga-DOTA-Siglec-9 was significantly higher in the FAP-IL2v-treated group than in the vehicle-treated group 7 days after baseline imaging, and this was confirmed by tumor autoradiography analysis. FAP-IL2v treatment did not affect VAP-1 expression on the tumor vasculature. However, FAP-IL2v treatment increased the number of CD8 + T cells and natural killer cells in tumors. The present study showed that [ 68 Ga]Ga-DOTA-Siglec-9 can detect B16-FAP tumors and allows monitoring of FAP-IL2v treatment., Competing Interests: SJ owns stock in Faron Pharmaceuticals. CK, VN, and MR declare employment, patents and ownership interest with Roche, and TN was employed by Roche at the time of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Viitanen, Virtanen, Liljenbäck, Moisio, Li, Nicolini, Richard, Klein, Nayak, Jalkanen and Roivainen.)

Sexual and reproductive health is a challenge worldwide, and much progress is needed to reach the relevant UN Sustainable Development Goals. This paper presents cross-sectional data collected in Sierra Leone on sexual and gender-based violence (SGBV), family planning (FP), child, early and forced marriage (CEFM), and female genital mutilation (FGM) using an innovative method of measurement: situational judgment tests (SJTs), as a subset of questions within a larger survey tool. For the SJTs, respondents saw hypothetical scenarios on these themes and had to indicate how they would react. The objective is to give an impression of beliefs and norms on specific behaviors, which provide insights for social and behavior change interventions. Data was collected by enumerators traveling to villages randomly selected in six districts of the country. The sample is composed of 566 respondents. Results show that FGM in particular seem to be a priority topic, in comparison to the other topics for which the norms seem to be stronger against those practices. Age differences emerged and suggest priority groups to be targeted (e.g., on the topic of female genital mutilation, younger female respondents, and older male respondents gave the lowest coded responses which reflected to less appropriate behavior in our coding). In terms of validity of the measurement methods, situational judgment test answers correlated positively with other items in the survey, but the magnitude of the association is often small, and sometimes not significant. Thus, more studies are needed to further explore the validity of this measure by comparing against a reference value. Using SJTs could complement other data collection tools to perform community assessment, and orient the direction of the program in its planning phase., Competing Interests: NC was employed by company Nadulpan. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moussaoui, Law, Claxton, Itämäki, Siogope, Virtanen, Desrichard and Consortium Sierra Leone Red Cross Society.)

We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032 distinct features. Multiomics factor analysis revealed distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet, and hormonal effects. For example, ethinyl estradiol, a common oral contraceptive, produced characteristic molecular and physiological effects, including increased levels of inflammation and impact on thyroid, cortisol levels, and pulse, that were distinct from other sources of variability observed in our study. In total, this work illustrates the value of combining deep molecular and digital monitoring of human health. A record of this paper's transparent peer review process is included in the supplemental information., Competing Interests: Declaration of interests O.K. received research funding from Vinnova for collaboration between Astra Zeneca, Takeda, Pelago, and Labcyte. O.K. is also a board member and a co-founder of Medisapiens and Sartar Therapeutics and has received a royalty on patents licensed by Vysis-Abbot. R.S. is currently employed at Crown CRO., (Copyright © 2021. Published by Elsevier Inc.)

Background & Aims: The enteric nervous system (ENS) is the largest part of the peripheral nervous system; moreover, abnormal ENS development and function are associated with multiple human pathologies. Data from several groups suggest that under normal physiological conditions in adult animals, enteric nerve cells do not replicate. A study by Kulkarni et al in 2017 challenged this view and proposed that nearly 70% of enteric neurons in the myenteric ganglia are born in 1 week. The authors of this study suggested that differences in DNA labelling times and DNA denaturation conditions might explain discrepancies with previous reports. Previous studies were carried out using different conditions and labelling techniques in various regions of the gastrointestinal tract; thus, conclusions have remained elusive., Methods: Here, we have eliminated those variables by analyzing the whole small intestine using the reagents and conditions that Kulkarni et al used. To exclude variables related to immunohistochemistry, we carried out parallel experiments with "click chemistry"-based detection of DNA replication., Results: Although proliferation was readily detected in the epithelium, we found no evidence of neuronal replication in the myenteric ganglia., Conclusions: We conclude that within 1 week under normal physiological conditions, myenteric neurons in the small intestine do not replicate., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims and Objectives: To systematically review existing literature exploring supportive interventions for family members of very seriously ill patients in inpatient care., Background: Being around a patient with a very serious illness in inpatient care setting is stressful and burdensome for family members. There is little information available on interventions that support family members of very seriously ill patients in inpatient care., Design: A systematic review., Methods: The literature review was conducted in May 2020 using four databases: PubMed (Medline), CINAHL, PsycINFO and Cochrane. A quality assessment was performed using the Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group by the National Heart, Lung, and Blood Institute. The PRISMA checklist was used to support specific reporting and the TIDieR checklist to form detailed descriptions of the interventions., Results: Of the 7165 identified studies, 11 studies were included in the review based on predetermined criteria. Interventions were based on meetings with family members, education or therapy. Mindfulness- and therapy-based interventions and multiple-session tailored interventions showed beneficial outcomes for psychological symptoms and educational interventions on preparedness and self-efficacy. Several different measuring instruments to evaluate similar outcomes, such as psychological symptoms and coping, were used., Conclusions: Only a few supportive interventions for family members of very seriously ill patients in inpatient care were found, which made comparing the differences in the varying study methods and outcomes difficult. More studies on supportive interventions and their feasibility and effectiveness are essential. Further evaluation of instruments is necessary to identify the most valid and reliable ways of measuring symptoms and coping., Relevance to Clinical Practice: The results of this study can be used in clinical practice when selecting effective interventions or assessing family members' need for support. Additionally, the results can be used for guidance when developing new, effective interventions., (© 2021 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Background: Immune-checkpoint inhibitors (ICIs) have introduced novel immune-related adverse events (irAEs), arising from various organ systems without strong timely dependency on therapy dosing. Early detection of irAEs could result in improved toxicity profile and quality of life. Symptom data collected by electronic (e) patient-reported outcomes (PRO) could be used as an input for machine learning (ML) based prediction models for the early detection of irAEs., Methods: The utilized dataset consisted of two data sources. The first dataset consisted of 820 completed symptom questionnaires from 34 ICI treated advanced cancer patients, including 18 monitored symptoms collected using the Kaiku Health digital platform. The second dataset included prospectively collected irAE data, Common Terminology Criteria for Adverse Events (CTCAE) class, and the severity of 26 irAEs. The ML models were built using extreme gradient boosting algorithms. The first model was trained to detect the presence and the second the onset of irAEs., Results: The model trained to predict the presence of irAEs had an excellent performance based on four metrics: accuracy score 0.97, Area Under the Curve (AUC) value 0.99, F1-score 0.94 and Matthew's correlation coefficient (MCC) 0.92. The prediction of the irAE onset was more difficult with accuracy score 0.96, AUC value 0.93, F1-score 0.66 and MCC 0.64 but the model performance was still at a good level., Conclusion: The current study suggests that ML based prediction models, using ePRO data as an input, can predict the presence and onset of irAEs with a high accuracy, indicating that ePRO follow-up with ML algorithms could facilitate the detection of irAEs in ICI-treated cancer patients. The results should be validated with a larger dataset. Trial registration Clinical Trials Register (NCT3928938), registration date the 26th of April, 2019.

Background: Clinical practice, clinical nursing teaching, curricula, working experience and previous healthcare degrees are factors related to the competence of graduating nursing students from the points of view of nursing students and clinical mentors. However, nurse educators' perceptions of these factors are lacking in previous studies, despite assessing student performance and competence is a core competence and one of the main duties of nurse educators., Objectives: The aim of this study was to describe nurse educators' perceptions of factors related to graduating nursing students' competence., Design: The study was conducted using a descriptive qualitative approach utilising focus group interviews in data collection., Participants: A purposive sample consisting of 23 volunteer nurse educators from five Finnish universities of applied sciences took part in seven group interviews., Methods: Data was collected in guided, semi-structured interviews, based on a literature review of previous studies. The data was analysed using a deductive-inductive content analysis., Results: According to nurse educators, six main categories describing factors related to graduating nursing students' competence were found: (1) commitment to the nursing profession, (2) experiences in healthcare, (3) learning abilities, (4) learning environments, (5) student characteristics and (6) the nurse educator's role., Conclusions: To ensure the adequate competence of the graduating nursing students, students' commitment to the nursing profession and their learning abilities and should be supported, and the quality of the learning environments, especially those of study groups and successful clinical practices, should be ensured during the education., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Patient education improves health and treatment adherence of patients with chronic kidney disease. However, evidence about the sufficiency of patients' knowledge processed in patient education is limited. The purpose of this study was to evaluate subjective and objective sufficiency of knowledge processed in patient education in dialysis care and treatment., Patients and Methods: A cross-sectional study design was used. The sample (n=162) comprised patients in predialysis or home dialysis. All eligible patients during the data collection timeframe (2016-2017) in two university hospital districts in Finland were invited to participate. Subjective sufficiency was evaluated with a structured questionnaire having 34 items divided into six dimensions of empowering knowledge (bio-physiological, functional, social, experiential, ethical, and financial) on a Likert scale (1=not sufficient at all, 4=very sufficient). Objective sufficiency was evaluated with a structured knowledge test with 10 items (score range 0-10, correct=1, wrong/no knowledge=0) based on the multidimensional content of patient education emphasizing bio-physiological dimension., Results: In subjective sufficiency of knowledge, the mean was 3.27 (SD 0.54). The bio-physiological dimension of empowering knowledge was the most sufficient (mean 3.52, SD 0.49) and the experiential the least (mean 2.8, SD 0.88). In objective sufficiency, the means ranged 5.15-5.97 (SD 2.37-2.68) among patients in different modalities of dialysis care and treatment. The least sufficient objective scores were bio-physiological and functional knowledge. The subjective and objective sufficiency did not correlate with each other., Conclusion: Patients' knowledge, either subjective or objective, does not seem to be sufficient. Hence, attention should be paid to supporting patients with more personalized knowledge. Furthermore, the relationship between subjective and objective sufficiency needs future consideration, as their non-correspondence was a new discovery., Competing Interests: Miss Saija Inkeroinen reports grants from Turku University Hospital, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2021 Inkeroinen et al.)

Purpose: To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer., Methods: Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0-500 and 0-2000 s/mm 2 , respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential)., Results: Significant changes were observed in DWI data during the tumor growth, indicated by ADC m , ADC s , and ADC k . Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1-4. The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model., Conclusion: Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Merisaari, Laakso, Liljenbäck, Virtanen, Aronen, Minn, Poutanen, Roivainen, Liimatainen and Jambor.)

MRI is a common method of prostate cancer diagnosis. Several MRI-derived markers, including the apparent diffusion coefficient (ADC) based on diffusion-weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlier with rotating frame relaxation times T RAFF2 and T RAFF4 than with the continuous wave T 1ρ , adiabatic T 1ρ , adiabatic T 2ρ , T 1 , T 2 or water ADC. Human PC3 prostate cancer cells expressing a red fluorescent protein were implanted in 21 male mice. Docetaxel chemotherapy was given once a week starting 1 week after cell implantation for 10 randomly selected mice, while the rest served as a control group (n = 11). The MRI consisted of relaxation along a fictitious field (RAFF) in the second (RAFF2) and fourth (RAFF4) rotating frames, T 1 and T 2 , continuous wave T 1ρ , adiabatic T 1ρ and adiabatic T 2ρ relaxation time measurements and water ADC. MRI was conducted at 7 T, once a week up to 4 weeks from cell implantation. The tumor volume was monitored using T 2 -weighted MRI and optical imaging. The histology was evaluated after the last imaging time point. Significantly reduced RAFFn, T 1ρ, T 2ρ and conventional relaxation times 4 weeks after tumor implantation were observed in the treated tumors compared with the controls. The clearest short- and long-term responses were obtained with T 1 , while no clear improvement in response to treatment was detected with novel methods compared with conventional methods or with RAFFn compared with all others. The tumor volume decreased after a two-week time point for the treated group and increased significantly in the control group, which was supported by increasing red fluorescent light emission in the control tumors. Decreased relaxation times were associated with successful chemotherapy outcomes. The results indicate altered relaxation mechanisms compared with higher dose chemotherapies previously published., (© 2021 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Sialic acid-binding immunoglubulinlike lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1. A 68 Ga-labeled peptide of Siglec-9, 68 Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-humans study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical. Methods: Six healthy men underwent dynamic whole-body PET/CT. Serial venous blood samples were drawn from 1 to 240 min after intravenous injection of 162 ± 4 MBq of 68 Ga-DOTA-Siglec-9. In addition to γ-counting, the plasma samples were analyzed by high-performance liquid chromatography to detect intact tracer and radioactive metabolites. Radiation doses were calculated using the OLINDA/EXM software, version 2.2. In addition, a patient with early rheumatoid arthritis was studied with both 68 Ga-DOTA-Siglec-9 and 18 F-FDG PET/CT to determine the ability of the new tracer to detect arthritis. Results: 68 Ga-DOTA-Siglec-9 was well tolerated by all subjects. 68 Ga-DOTA-Siglec-9 was rapidly cleared from the blood circulation, and several radioactive metabolites were detected. The organs with the highest absorbed doses were the urinary bladder wall (0.38 mSv/MBq) and kidneys (0.054 mSv/MBq). The mean effective dose was 0.022 mSv/MBq (range, 0.020-0.024 mSv/MBq). Most importantly, however, 68 Ga-DOTA-Siglec-9 was comparable to 18 F-FDG in detecting arthritis. Conclusion: Intravenous injection of 68 Ga-DOTA-Siglec-9 was safe and biodistribution was favorable for testing of the tracer in larger group of patients with rheumatoid arthritis, as is planned for the next phase of clinical trials. The effective radiation dose of 68 Ga-DOTA-Siglec-9 was within the same range as the effective radiation doses of other 68 Ga-labeled tracers. Injection of 150 MBq of 68 Ga-DOTA-Siglec-9 would expose a subject to 3.3 mSv. These findings support the possible repeated clinical use of 68 Ga-DOTA-Siglec-9, such as in trials to elucidate the treatment efficacy of novel drug candidates., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

The aim of this descriptive study was to analyze the relationship between the sufficiency and usefulness of patient education from the perspective of people with chronic kidney disease. The goal was to discover whether both sufficiency and usefulness need to be analyzed in the quality evaluation of patient education. Patients undergoing predialysis or home dialysis care in Finland (N = 162) evaluated both the sufficiency and usefulness of patient education provided by nephrology nurses by using parallel structured questionnaires. A strong relationship was found between the sufficiency and usefulness of patient education. The relationship was significant across all dimensions of empowering knowledge, but no systematic association was found between the sufficiency-usefulness relationship and background variables. Depending on the purpose of evaluating patient education, either aspect, that is, sufficiency or usefulness, can be used, but it is not necessary to use both due to their strong inter-correlation. In terms of implications for practice, consideration of both sufficiency and usefulness is important when providing empowering patient education for people undergoing pre- or home dialysis, but only one aspect needs to be evaluated., (© 2020 John Wiley & Sons Australia, Ltd.)

Background: Immune checkpoint inhibitors (ICIs) have become a standard of care for various tumor types. Their unique spectrum of side effects demands continuous and long-lasting assessment of symptoms. Electronic patient-reported outcome (ePRO) follow-up has been shown to improve survival and quality of life of cancer patients treated with chemotherapy., Objective: This study aimed to investigate whether ePRO follow-up of cancer patients treated with ICIs is feasible. The study analyzed (1) the variety of patient reported symptoms, (2) etiology of alerts, (3) symptom correlations, and (4) patient compliance., Methods: In this prospective, one-arm, multi-institutional study, we recruited adult cancer patients whose advanced cancer was treated with anti-programmed cell death protein 1 (PD)- ligand (L)1 agents in outpatient settings. The ePRO tool consisted of a weekly questionnaire evaluating the presence of typical side effects, with an algorithm assessing the severity of the symptom according to National Cancer Institute Common Terminology Criteria for Adverse Events and an urgency algorithm sending alerts to the care team. A patient experience survey was conducted monthly. The patients were followed up to 6 months or until disease progression., Results: A total of 889 symptom questionnaires was completed by 37 patients (lung cancer, n=15; melanoma, n=9; genitourinary cancer, n=9; head and neck cancer, n=4). Patients showed good adherence to ePRO follow-up. The most common grade 1 symptoms were fatigue (28%) and itching (13%), grade 2 symptoms were loss of appetite (12%) and nausea (12%), and grade 3-4 symptoms were cough (6%) and loss of appetite (4%). The most common reasons for alerts were loss of appetite and shortness of breath. In the treatment benefit analysis, positive correlations were seen between clinical benefit and itching as well as progressive disease and chest pain., Conclusions: According to the results, ePRO follow-up of cancer patients receiving ICIs is feasible. ePROs capture a wide range of symptoms. Some symptoms correlate to treatment benefit, suggesting that individual prediction models could be generated., Trial Registration: Clinical Trials Register, NCT3928938; https://clinicaltrials.gov/ct2/show/NCT03928938., (©Sanna Iivanainen, Tuomo Alanko, Pia Vihinen, Teemu Konkola, Jussi Ekstrom, Henri Virtanen, Jussi Koivunen. Originally published in JMIR Formative Research (http://formative.jmir.org), 28.10.2020.)

Objectives: The aim of this work was to survey how well adolescents with type 1 diabetes mellitus (T1D) of legal driving age understand the risks associated with driving with diabetes and report adherence to recommendations., Methods: This study was a cross-sectional survey of 191 adolescents, 14 to 18 years of age, with T1D., Results: The average (standard deviation [SD]) glycated hemoglobin of respondents with a learner's or a driver's license was 9.0% (SD, 1.9%) and 8.9% (SD, 1.9%), respectively (p=0.91). The proportions of adolescents with a learner's or a driver's license who almost always or always checked their blood glucose prior to driving was 69% and 41%, respectively (p=0.01). Eighteen percent of adolescents with a learner's license and 41% with a driver's license experienced hypoglycemia while driving. The average number of weekly hypoglycemic events in each group was 2.0 (SD, 1.4) and 2.3 (SD, 2.0), respectively. There was a higher reported frequency of weekly mild hypoglycemic events between drivers who reported pulling over at least once while driving due to symptoms of hypoglycemia (3.25±2.38) and those who reported never having pulled over for hypoglycemia (1.87±1.31) (p=0.012). Respondents with a learner's license reported higher adherence to guidelines than those with a full license., Conclusions: Clinical education needs to reinforce adherence to recommendations, particularly checking blood glucose or wearing a continuous glucose monitor prior to driving, for all adolescents of driving age. The frequency of mild hypoglycemic events per week is associated with self-reported hypoglycemic events while driving., (Copyright © 2019 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Dialysis patients' experience of safety can be seen positively connected with their wellbeing and successful outcomes of their treatment and care. Therefore, it is necessary to identify the factors promoting and weakening the safety experiences and create a basis for empowering interventions., Objectives: Analyse patients' experiences of safety with dialysis and the factors promoting and weakening their safety., Methods: A descriptive study design was used. This study analysed Finnish patients' (n = 70) experiences of safety with dialysis and the factors promoting and weakening patients' safety. Data were collected using a questionnaire including one structured question and two open questions., Findings: The patients experienced their care as safe. Thematic analysis provided three factors promoting patients' safety: certainty of patient's own competence in dialysis self-management, competence of personnel in dialysis treatment and care, continuity of ensuring patients' state of health, as well as three factors weakening safety: patients' uncertainty of living with chronic kidney disease, insufficient patient education and uncertain realisation of dialysis treatment and care., Conclusion: This study provided new insight into understanding patients' experiences of safety with dialysis. We show that the factors connected with patients' safety were related to the successful realisation of self-management, support for the self-management, and delivery of dialysis treatment and care anticipating high-level outcomes. In light of this study, there are development needs in dialysis treatment and care as a whole in order to ensure patients' safety., (© 2019 European Dialysis and Transplant Nurses Association/European Renal Care Association.)

Context: Patients with type 1 diabetes (T1D) have lower microbiota diversity and distinct gut microbial profiles that have been linked to changes in intestinal permeability. Prebiotics are nondigestible carbohydrates that alter gut microbiota and could potentially improve glycemic control and reduce intestinal permeability and thereby insulin sensitivity., Objective: To determine the effect of prebiotics on glycemic control, gut microbiota, and intestinal permeability in children with T1D., Design: A randomized, placebo-controlled trial in children 8 to 17 years of age with T1D using placebo or prebiotic oligofructose-enriched inulin for 12 weeks. Baseline, 3-month, and 6-month assessments included HbA1c, C-peptide, gut microbiota, intestinal permeability, frequency of diabetic ketoacidosis (DKA), and severe hypoglycemia., Results: Forty-three subjects were randomized and 38 completed the study. The groups were similar at baseline: prebiotic (N = 17), age 12.5 years (SD of 2.8), HbA1c 8.02% (SD of 0.82); placebo (N = 21), age 12.0 years (SD of 2.6), HbA1c 8.08% (SD of 0.91). No significant differences were found in the frequency of DKA or severe hypoglycemia. At 3-months, C-peptide was significantly higher (P = 0.029) in the group who received prebiotics, which was accompanied by a modest improvement in intestinal permeability (P = 0.076). There was a significant increase in the relative abundance of Bifidobacterium within the prebiotic group at 3 months that was no longer present after the 3-month washout. The placebo group had significantly higher relative abundance of Streptococcus, Roseburia inulinivorans, Terrisporobacter, and Faecalitalea compared with the prebiotic group at 3 months., Conclusion: Prebiotics are a potentially novel, inexpensive, low-risk treatment addition for T1D that may improve glycemic control. Further larger-scale trials are needed., (Copyright © 2019 Endocrine Society.)

Aim: The aim of this review was to identify and summarize the required competences of nursing PhD students and postdoctoral researchers to pursue a successful researcher career and to compare these competences with the existing competence frameworks., Design: Scoping review., Methods: PubMed, CINAHL, SocIndex, PsycInfo, Eric, EMBASE, Academic Search Premier and Scopus databases were searched from January 1990-December 2018. The guidelines of PRISMA Extension for Scoping Reviews and the scoping review framework by Arksey and O'Malley (2005, International Journal of Social Research Methodology, 8, 19) were applied., Results: Forty-four studies were reviewed comprising 15 competence domains. Competences corroborated the competences defined in the competence frameworks. However, the qualitative and descriptive research designs rendered a modest level of evidence and generalizability., Competing Interests: No conflict of interest has been declared by the authors., (© 2019 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Corneal confocal microscopy (CCM) has been used to identify corneal nerve damage and increased Langerhans cell (LC) density in adults with Type 1 diabetes mellitus (T1DM). The purpose of this study was to evaluate whether corneal confocal microscopy can identify early corneal nerve damage and change in LC density in children and adolescents with T1DM. 64 participants with T1DM (age-14.6 ± 2.5 years, duration of diabetes-9.1 ± 2.7 years, HbA1c-75.66 ± 2.53 mmol/mol [9.1 ± 1.8%]) and 48 age-matched healthy control subjects underwent CCM. Sub-basal corneal nerve morphology and the density of mature and immature LCs was quantified. Corneal nerve fibre length and branch density were lower, whilst fibre density and tortuosity did not differ and both immature and mature LC density was significantly higher in T1DM compared to control subjects. There was no association between HbA1c and duration of diabetes with nerve fibre parameters or LC's density. Children and adolescents with T1DM demonstrate early immune activation and nerve degeneration.

Purpose: Patient-reported outcome (PRO) follow-up has been shown to improve quality of life (QoL) and survival of cancer patients receiving chemotherapy. Kaiku Health application is a web-based electronic PRO (ePRO) tool which is designed for follow-up of cancer patients receiving immune checkpoint inhibitors (ICI). Purpose of the current study is to investigate whether symptoms collected by Kaiku Health ePRO tool on cancer patients receiving immune checkpoint inhibitors (ICI) follows to symptoms reported in clinical trials and whether coupling of specific symptoms does occur., Methods: We retrospectively collected data on symptom timing and severity, and QoL of patients followed with Kaiku Health IO module in two Finnish cancer centers between 2017 and 2018. Kaiku Health IO module consists of 18 adaptive questions, which assess the presence and severity of symptoms. Patients were requested (via e-mail) to fill online symptom questionnaires with 3-7 day interval and QoL questionnaires (QLQ-C30) with 1-2 month interval., Results: The IO module was used to follow 37 patients who had filled in total 559 symptom questionnaires. There was good adherence to ePRO follow-up with a median of 11 questionnaires filled per patient. The reported symptoms and their severity follow closely what has been seen in clinical trials investigating ICIs. Correlation analysis of the symptoms showed the strongest positive correlations between itching and rash; nausea and vomiting, decreased appetite, or stomach pain; cough and shortness of breath., Conclusions: The results of the current study suggest that real-world symptom data collected through the ePRO application on cancer patients receiving ICI therapy aligns with the data from clinical trials. Correlations between different symptoms occur, which might reflect therapeutic efficiency, side effects, or tumor progression. These correlations should be further investigated with data coupled to clinical outcomes.

Background: Population-, assay-, and trimester-specific reference intervals for thyroid function tests are necessary to assess thyroid status accurately and manage thyroid disease throughout pregnancy. This study's objective was to verify if the manufacturer's recommended trimester-specific reference intervals for thyroid tests and the American Thyroid Association's recommended total thyroxine (TT4) pregnancy reference intervals were verifiable and appropriate for use in the authors' multicultural population., Methods: Blood samples were obtained from the following sources: stored frozen surplus blood from women undergoing routine aneuploidy screening (first- and second-trimester samples, n = 274), women participating in an observational cohort study (second- and third-trimester samples, n = 135), and blood collected from women presenting for assessment to the labor and delivery ward (third-trimester samples, n = 35). Exclusions included thyroid medication or disease and positive thyroid peroxidase antibodies (anti-TPO). Samples were analyzed for thyrotropin (TSH), free T4 (fT4), free triiodothyronine (fT3), TT4, and anti-TPO using the Roche Cobas 8000 Modular e602 electrochemiluminescence immunoassay., Results: Nine percent of the aneuploidy screening samples were excluded prior to thyroid testing due to maternal use of thyroid medication. Six percent of analyzed samples were excluded: 5.9% with positive anti-TPO and one with a TSH >10 mIU/L. The manufacturer's recommended trimester-specific reference intervals for TSH were not verified by described standardized methods. Therefore, 95th percentile reference intervals were determined using a minimum number of samples. Reference intervals for TSH and fT4 were as follows: 9-12 weeks, 0.18-2.99 mIU/L and 11-19.2 pmol/L; second trimester, 0.11-3.98 mIU/L and 10.5-18.2 pmol/L; and third trimester, 0.48-4.71 mIU/L and 9.0-16.1 pmol/L, respectively. The TT4 reference interval after 19 weeks' gestation was 77-186 nmol/L., Conclusions: This study provides a simple approach to verify or establish trimester-specific thyroid function reference intervals in local populations. The TT4 reference interval was lower than the interval proposed by the American Thyroid Association, suggesting the need for further study of TT4 in pregnancy and reliance on locally established fT4 reference intervals after 19 weeks, especially when there are no equivalent reference intervals for TT4.

Objective: To survey adolescents with type 1 diabetes mellitus (T1DM) about their knowledge and application of harm-reduction recommendations when they engage in alcohol and other illicit substance use., Methods: Cross-sectional survey and chart review of adolescents with T1DM aged 13 to 18 years., Results: One hundred and ninety patients were approached and 164 were included in the analysis. Mean age was 15.6 years (standard deviation [SD]=1.5). Fifty-one per cent were male. Of those who reported consuming alcohol, 95% knew that they should have a friend or parent check their blood glucose in the middle of the night after drinking but only 62% reported actually doing this in practice. Similarly, 98% reported knowing that they should wear a medic alert identification but only 79% reported actually doing this. Of those who reported consuming cannabis, 14% reported forgetting to check blood glucose and 14% reported forgetting insulin when using cannabis. From the chart review, a significantly lower proportion of adolescents reported substance use during their clinic visits (alcohol 26%, tobacco 19%, illicit substance 25%) compared to the self report in the survey (alcohol 55%, tobacco 30%, illicit substance 32%)., Conclusions: Adolescents' knowledge of harm-reduction practices for the use of alcohol and other illicit substances is not always put to practice. Motivating adolescents to use their knowledge in practice is an important area to improve in diabetes self-management. Those who reported engaging in substance use in the survey had not always reported use during interactions with health care providers. This emphasizes the need for unbiased, universal education of all adolescents in the clinic.

Over the past decade, there has been a substantial increase in the number of beverage products containing added vitamins and minerals. Often viewed as a healthier choice by consumers, the metabolic impacts of excessive vitamin consumption are relatively unknown, especially in children. The aim of this study was to examine the effects of a widely available, vitamin fortified beverage (5h Energy Decaffeinated) on insulin sensitivity, metabolic hormones and serum metabolomic responses in adolescents. Twenty adolescents (13-19y, 10M/10F) completed two randomized trials, consuming either coloured water as placebo (PL) or a vitamin fortified, sugar free beverage (FB, 1.5ml/kg) 40min prior to a modified oral glucose tolerance test (OGTT, 1.75g/kg glucose). Samples were collected at baseline and at 30, 45, 60, 90 and 120min during the OGTT. No differences in blood glucose response were observed between the treatments. However, compared to PL, postprandial plasma C-peptide and insulin excursion was significantly greater with FB, resulting in a 28% decline in the insulin sensitivity index. This was accompanied by elevated GLP-1, glucagon and PYY responses with FB compared to PL. Serum metabolomics (1H-NMR) analysis also revealed perturbations to vitamin B-linked one carbon metabolism flux with FB consumption that became more pronounced over time. These included a transient reduction in homocysteine flux accompanied by increases in betaine, vitamin B6, vitamin B12, choline, folate and taurine. Although these impacts are likely short-lived, results show that beverages fortified with excessive amounts of vitamins are not metabolically inert, but likely result in greater insulin secretion, differential gut hormone secretion and elevated one-carbon flux to process the excessive vitamin loads., Competing Interests: The authors have declared that no competing interests exist.

Background: Finnish men used to have higher semen quality than Danish men. However, recent studies showed that semen quality in Finland has declined, but it has been relatively stable in Denmark., Objective: This study aimed to compare new data on semen quality of the young Finnish men to that of Danish men., Materials and Methods: In this cross-sectional study, 18- to 19-year-old men residing in Turku, Finland and Copenhagen, Denmark, were invited to participate in 2008-2011. Each man filled in a questionnaire, provided one semen sample and underwent andrological examination. Semen samples were analyzed according to WHO. Multiway ANOVA was used to adjust semen variables for duration of sexual abstinence and age (and time from ejaculation to the start of semen analysis for sperm motility)., Results: Altogether 287 Finnish men and 873 Danish men participated in the study. The adjusted median sperm concentrations were 49 and 47 million/mL for Finnish and Danish men, respectively (p = 0.48). The adjusted median total sperm counts were 148 million in Finland and 146 million in Denmark (p = 0.87). The adjusted median percentages of morphologically normal spermatozoa were 6.9% in Finland and 6.5% in Denmark, p = 0.27. Finnish men had higher adjusted median percentages of motile spermatozoa (A+B+C) than Danish men (80% vs. 69%, p < 0.001). The proportion of men who had low semen quality (sperm concentration, percentage of morphologically normal spermatozoa or percentage of progressively motile spermatozoa below WHO reference limits) was lower in Finland (25.4%) than in Denmark (34.6%), p = 0.004., Discussion: Considerable percentage of men in both countries had low semen quality. The deteriorating semen quality in Finland may result in decreasing fecundity, which is a cause of concern., Conclusion: The formerly high semen quality in Finland has converged to the lower Danish levels. Our findings demonstrate the importance of continuing surveillance of semen quality., (© 2018 American Society of Andrology and European Academy of Andrology.)

Background: Microbial biosynthesis of alkanes is considered a promising method for the sustainable production of drop-in fuels and chemicals. Carbon dioxide would be an ideal carbon source for these production systems, but efficient production of long carbon chains from CO 2 is difficult to achieve in a single organism. A potential solution is to employ acetogenic bacteria for the reduction of CO 2 to acetate, and engineer a second organism to convert the acetate into long-chain hydrocarbons., Results: In this study, we demonstrate alkane production from CO 2 by a system combining the acetogen Acetobacterium woodii and a non-native alkane producer Acinetobacter baylyi ADP1 engineered for alkane production. Nine synthetic two-step alkane biosynthesis pathways consisting of different aldehyde- and alkane-producing enzymes were combinatorically constructed and expressed in A. baylyi . The aldehyde-producing enzymes studied were AAR from Synechococcus elongatus , Acr1 from A. baylyi , and a putative dehydrogenase from Nevskia ramosa . The alkane-producing enzymes were ADOs from S. elongatus and Nostoc punctiforme , and CER1 from Arabidopsis thaliana . The performance of the pathways was evaluated with a twin-layer biosensor, which allowed the monitoring of both the intermediate (fatty aldehyde), and end product (alkane) formation. The highest alkane production, as indicated by the biosensor, was achieved with a pathway consisting of AAR and ADO from S. elongatus . The performance of this pathway was further improved by balancing the relative expression levels of the enzymes to limit the accumulation of the intermediate fatty aldehyde. Finally, the acetogen A. woodii was used to produce acetate from CO 2 and H 2 , and the acetate was used for alkane production by the engineered A. baylyi , thereby leading to the net production of long-chain alkanes from CO 2 ., Conclusions: A modular system for the production of drop-in liquid fuels from CO 2 was demonstrated. Among the studied synthetic pathways, the combination of ADO and AAR from S. elongatus was found to be the most efficient in heterologous alkane production in A. baylyi . Furthermore, limiting the accumulation of the fatty aldehyde intermediate was found to be beneficial for the alkane production. Nevertheless, the alkane productivity of the system remained low, representing a major challenge for future research.

Dual longitudinal mode distributed feedback lasers have been fabricated using surface gratings with and without apodization. Analytic formulas and simulations that have been used to derive design guidelines are presented. The fabricated device characteristics are in good agreement with the simulations. The grating apodization enables a lower threshold current density, a higher output power and a broader range of difference frequency tunability by bias, which can be extended beyond the measured 15-55 GHz by changing the device structure. The apodization and the complex coupling of the surface gratings reduce the effects of the uncontrollable phase of facet reflections, enabling the use of higher facet reflectivities, which leads to narrower intrinsic short time-scale linewidths.

Background: Youth with chronic conditions may engage in risky behaviour to the same, if not higher, degree as their healthy peers., Objectives: To determine the prevalence of alcohol, tobacco, cannabis and illicit substance use in adolescents with type 1 diabetes (T1DM) compared to a general adolescent population., Methods: Cross-sectional survey of adolescents with T1DM (13 to 18 years). A published contemporary Canadian youth survey on use of alcohol, tobacco and illicit drugs was used as data representative of the general adolescent population. Outcome measures between the T1DM and general group were compared using Chi-square and Fisher's exact test where appropriate., Results: One hundred and sixty-four adolescents with T1DM (mean 15.6 years [SD 1.5]; 51.3% male) were participated. The proportions of adolescents with T1DM who have tried substances were: alcohol 51.8%, tobacco 27.4%, cannabis 22.6% and other illicit substances 7.3%. Compared to the general population (n=3469), there were no significant differences in the proportion of adolescents that reported ever consuming alcohol, tobacco or cannabis. Reported illicit substance use was significantly lower in adolescents with T1DM compared to general population (7.3% versus 36.0%, P<0.0001)., Conclusions: Proportions reporting having ever consumed alcohol, tobacco or cannabis were not significantly different between the two groups. However, the proportion of adolescents with T1DM who reported ever consuming an illicit substance was different from the comparison group. It is important to explore risky behaviours with adolescents with T1DM and focus on prevention and education during routine clinic visits.