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Abstract Engineered biological neural networks are indispensable models for investigation of neural function and dysfunction from the subcellular to the network level. Notably, advanced neuroengineering approaches are of significant interest for their potential to replicate the topological and functional organization of brain networks. In this study, we reverse engineered feedforward neural networks of primary cortical and hippocampal neurons, using a custom-designed multinodal microfluidic device with Tesla valve inspired microtunnels. By interfacing this device with nanoporous microelectrodes, we show that the reverse engineered multinodal neural networks exhibit capacity for both segregated and integrated functional activity, mimicking brain network dynamics. To advocate the broader applicability of our model system, we induced localized perturbations with amyloid beta to study the impact of pathology on network functionality. Additionally, we demonstrate long-term culturing of subregion- and layer specific neurons extracted from the entorhinal cortex and hippocampus of adult Alzheimer’s-model mice and rats. Our results thus highlight the potential of our approach for reverse engineering of anatomically relevant multinodal neural networks to study dynamic structure-function relationships in both healthy and pathological conditions.

Youth in the US experience high rates of sexual violence. Historically, adults design and deliver preventive initiatives, with youth limited to participants and recipients. The use of community-based participatory research and other participatory approaches can expand the reach and impact of adolescent sexual violence prevention initiatives by positioning youth as leaders and co-researchers. This systematic review explores both adolescent violence prevention programs and research projects that take a participatory, youth-engaged, or youth-led approach. This review aims to understand what activities youth are involved in and how they are equipped for their roles. Following PRISMA guidelines, the review located eight eligible articles that involved high school youth or younger as more than data, focused on adolescent sexual or dating violence prevention, and whose programs or studies were conducted in the United States. I reviewed each article for programmatic and study specifics, with special attention to which stages youth participated in and how capacity-building was incorporated. The results revealed that youth can participate in a variety of activities, though they are involved in certain stages more than others, and that capacity-building ranged in breadth and frequency. I call researchers to detail youth activities and training, and explain clearly their participatory approach and decisions.

Abstract Background Multimorbidity is increasingly acknowledged as a significant health concern, particularly among older individuals. It is associated with a decline in quality of life and psychosocial well-being as well as an increased risk of being referred to multiple healthcare providers, including more frequent admissions to emergency departments. Person-centered care interventions tailored to individuals with multimorbidity have shown promising results in improving patient outcomes. Research is needed to explore how work practices within integrated care models are experienced from Registered Nurse Case Managers’ (RNCMs) perspective to identify areas of improvement. Therefore, the aim of this study was to describe RNCMs’ work experience with a person-centered collaborative healthcare model (PCCHCM). Methods This study used an inductive design. The data were collected through individual interviews with 11 RNCMs and analyzed using qualitative content analysis. Results Data analysis resulted in four generic categories: ‘Being a detective, ‘Being a mediator’, ‘Being a partner’, and ‘Being a facilitator of development’ which formed the basis of the main category ‘Tailoring healthcare, and social services to safeguard the patient’s best.’ The findings showed that RNCMs strive to investigate, identify, and assess older persons’ needs for coordinated care. They worked closely with patients and their relatives to engage them in informed decision-making and to implement those decisions in a personalized agreement that served as the foundation for the care and social services provided. Additionally, the RNCMs acted as facilitators of the development of the PCCHCM, improving collaboration with other healthcare professionals and enhancing the possibility of securing the best care for the patient. Conclusions The results of this study demonstrated that RNCMs tailor healthcare and social services to provide care in various situations, adhering to person-centered care principles and continuity of care. The findings underline the importance of implementing integrated care models that consider the unique characteristics of each care context and adapt different case managers’ roles based on the patient’s individual needs as well as on the specific needs of the local setting. More research is needed from the patients’ and their relatives’ perspectives to deepen the understanding of the PCCHCM concerning its ability to provide involvement, security, and coordination of care.

Abstract Common half-cell measurements deliver oxygen reduction activities linked to the chosen scan rate, limiting their value for fundamental and comparative studies on platinum. Here we show a deconvolution of the intrinsic kinetics from the effect of surface oxygen on platinum. We find an electronic effect of the surface oxygen, substantiate a Tafel slope of ~120 mV/decade, obtain an exchange current density of 13 ± 4 µA/cm2, and an activity of 7 mA/cm2 at 900 mV. Eventually, we broaden the scope of this analysis to the effects of surface rearrangement, alloying, and supported Pt nanoparticles, the latter providing insight into discrepancies between half-cell and fuel cell measurements. We find through computational methods that binding energies of intermediates would be weakened by the presence of highly coordinated oxygen atoms. Finally, we obtain a phenomenological rate equation for the oxygen reduction and evolution reaction, suggesting that both reactions follow a shared mechanism.

Abstract Background Maternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the autoimmunity per se. Methods We conducted a retrospective study of two pregnancy cohorts in the Danish population. The nationwide cohort (n = 1,014,775) was register-based and included all singleton pregnancies in Denmark from 1999–2015. The regional cohort (n = 14,573) included the biochemical measurement of thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region from 2011–2015 who had a blood sample drawn in early pregnancy as part of routine prenatal screening for chromosomal anomalies. The associations between diagnosed and biochemically assessed hypothyroidism and a diagnosis of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders, such as maternal age, diabetes, and parity. Results In the nationwide cohort, 2.2% of pregnant women with no history of hypothyroidism (reference group (ref.)) were diagnosed with preeclampsia, whereas the prevalence was 3.0% among pregnant women with hypothyroidism (aOR 1.3 (95% CI: 1.2–1.4)) and 4.2% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.6 (95% CI: 1.3–2.0)). In the regional cohort, 2.3% of women with early pregnancy TSH 60 U/mL) or Tg-Ab (> 33 U/mL) in early pregnancy (aOR 0.86 (95% CI: 0.6–1.2)). Conclusions In two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia.

Abstract Background Social support provided by a family member has been found to have a buffering effect on distress and is associated with better diabetes self-care. This study explores the meaning of social support, as described by close family members of foreign-born people living with type 2 diabetes (PWDM) in Sweden. It also explores the support provided by family members, and the support they need to be able to support the PWDM. Methods Qualitative explorative study, semi-structured interviews for data collection. Qualitative content analysis based on a theoretical framework on social support. Purposive sample of 13 family members, 18–52-years-old, born in countries in the Middle East, Africa, and Russia. Results The meaning of support was described as social and emotional. Most participants described a stressful situation; feelings of sadness/worry about the risk of the PWDM developing complications added to a strained life situation from which one could not opt out. Frequent daily contacts in a family network were evident, particularly by children trained as healthcare professionals. Caring for a family member was considered a filial piety, but it was also a chance to reciprocate. The support provided was mainly informational (e.g., reminders about nutritional intake), but it was also instrumental/practical (administering medicines, helping with economy/logistics, planning/cooking meals, basic care) and emotional (sharing meals, thoughts, and activities). The support the family members needed was getting first-hand information by attending the physician visits, being able to book appointments themselves at suitable times, and preventing the withholding of important information about the PWDM. They also desired an open telephone-line, oral and written information, particularly on diet. Conclusions To family-members, supporting the PWDM was normal and a filial piety. Support provided and needed was not only informational but also instrumental/practical and emotional. In diabetes care, addressing foreign-born individuals, diabetes education needs to be developed, also including family members. Informational material, particularly on diet, and improved access to healthcare and information about the healthcare system have the potential to increase family members’ control over the situation and prevent a negative trajectory in caregiving with perceived demands causing high levels of stress.

The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease-associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.

Abstract Background The ongoing global migration has led to multicultural societies, with many migrants who do not speak the official language in the host country. This could contribute to communication problems with staff in healthcare and a risk to patient safety. Research on patient safety in medication use in migrants is an under-researched area. The aim was to explore diverse foreign-born people’s experiences and perceptions of self-management of medication and determine if home-based practice patterns have implications on medication safety, and what factors may support safe medication use. Methods A qualitative explorative study, with individual semi-structured interviews and participant observations in the patients’ home. Qualitative content analysis was applied. Results A purposeful sample of 15 foreign-born persons identified by healthcare staff as having language difficulties in Swedish that may pose a safety risk in connection with medication use at home, was selected. Three categories were identified. The first category showed respondents being dependent on another person, having experiences of not receiving information about their medications due to language barriers, having difficulties getting access to the healthcare centre and feeling distrusted/misunderstood. The second category showed respondents being independent and self-motivated Although they struggled, they managed to get access/contact with the healthcare centre themselves and felt understood/listened to by the staff. The last category concerned factors that facilitating medication use; such as having a medication list in the respondents’ own language and offering a choice of language on the answering machine at the healthcare centre. Although they knew it was impossible to get an interpreter at the pharmacy, they felt safe knowing there was always a solution for receiving understandable information. Conclusion The findings highlighted that language barriers can complicate the communication between migrants and the healthcare, which can affect the medication safety. Understanding of this group is essential to improve the cooperation between patients and staff, leading to culturally congruent care. This knowledge should be used in healthcare to understand the gap in communication to increase patient safety. Further research from other angles, e.g. pharmacy/healthcare staff and relatives is needed to identify and evaluate facilitation to improve the outcome of the intended medication treatment.

Background The advent of biosimilars may increase the frequency of dose escalation with biologics in psoriasis.Objective To explore the frequency and outcomes of dose escalation with adalimumab etanercept, and ustekinumab.Methods Data were extracted from DermaReg-Pso, a psoriasis register in Stockholm, Sweden. The main exposure was treatment, and the main outcome was dose escalation. We describe outcomes with dose escalation by estimating drug survival and changes in the Psoriasis Area and Severity Index (PASI).Results 554 patients had 946 treatment episodes with adalimumab, etanercept, or ustekinumab. The cumulative incidence of dose escalation was 4.1 per 100 treatment years. The Hazard Ratios (HRs) for dose escalation with ustekinumab vs adalimumab and ustekinumab vs etanercept were 1.93 (95% CI: 1.25-2.98), and 2.20 (95% CI: 1.42-3.41), respectively. After dose escalation, the HRs for treatment discontinuation with adalimumab and etanercept compared with ustekinumab were 3.10 (95% CI: 1.56-6.18) and 7.15 (95% CI: 3.96-12.94), respectively. PASI was higher after compared to before dose escalation for etanercept (p = 0.036), but not for adalimumab (p = 0.832) or ustekinumab (p = 0.300).Conclusions Dose escalation was comparatively more frequent with ustekinumab than with adalimumab or etanercept; however, treatment discontinuation after dose escalation was more common with adalimumab and etanercept than ustekinumab.

Summary: Aim: To determine the level of knowledge and explore the difference of hand hygiene between nursing students and nurses. Background: Annually, 3.8 million people in Europe acquire healthcare-associated infections, highlighting the importance of hand hygiene. Despite WHO's emphasis on the fact that greater hand hygiene knowledge correlates with improved hand hygiene compliance, several studies have shown knowledge gaps among nurses and nursing students regarding hand hygiene. Design: Descriptive cross-sectional comparative survey. Methods: A version of the WHO “Hand Hygiene Knowledge Questionnaire”, translated into Swedish, was used for data collection among nursing students in the first and last semester, and registered nurses from a university and associated hospital. Data were analyzed by descriptive statistics, and comparison between groups with Fisher's exact test, one-way ANOVA, and post-hoc tests (Pairwise Z-Tests, Tukey HSD). Results: The survey, conducted between December 2020 and January 2021, received responses from 201 participants, including 71 first semester students, 46 last semester students and 84 registered nurses, showing moderate (55.7% [50–74% correct answers]) to good (43.8% [75–100% correct answers]) knowledge levels. First-semester students scored lower (17.0 ± 2.1) than last-semester students (18.8 ± 1.8) and registered nurses (18.3 ± 2.1) out of 25 questions. Discussion: It is necessary for all groups to receive proper education on hand hygiene knowledge and to have an educational program that does not separate the groups but combines them with continuing education, since the students will someday be influencing future hand hygiene knowledge as a peer, together with the nurse.

Clinical and preclinical studies suggest that some of the behavioral alterations observed in schizophrenia (SZ) may be mechanistically linked to synaptic dysfunction of glutamatergic signaling. Recent genetic and proteomic studies suggest alterations of cortical glutamate receptors of the AMPA-type (AMPARs), which are the predominant ligand-gated ionic channels of fast transmission at excitatory synapses. The impact of gene and protein alterations on the electrophysiological activity of AMPARs is not known in SZ. In this proof of principle work, using human postmortem brain synaptic membranes isolated from the dorsolateral prefrontal cortex (DLPFC), we combined electrophysiological analysis from microtransplanted synaptic membranes (MSM) with transcriptomic (RNA-Seq) and label-free proteomics data in 10 control and 10 subjects diagnosed with SZ. We observed in SZ a reduction in the amplitude of AMPARs currents elicited by kainate, an agonist of AMPARs that blocks the desensitization of the receptor. This reduction was not associated with protein abundance but with a reduction in kainates potency to activate AMPARs. Electrophysiologically-anchored dataset analysis (EDA) was used to identify synaptosomal proteins that linearly correlate with the amplitude of the AMPARs responses, gene ontology functional annotations were then used to determine protein-protein interactions. Protein modules associated with positive AMPARs current increases were downregulated in SZ, while protein modules that were upregulated in SZ were associated with decreased AMPARs currents. Our results indicate that transcriptomic and proteomic alterations, frequently observed in the DLPFC in SZ, converge at the synaptic level producing a functional electrophysiological impairment of AMPARs.

Abstract Objective/Background The Consensus Sleep Diary (CSD) is widely used to assess subjective sleep. Psychometric evaluations and focus-groups support its validity and clinical usefulness, but further research into its validity is needed. The aim of the study was to evaluate a Swedish translation of the CSD regarding test content and response processes in patients with insomnia. Patients/Methods In connection with translating the CSD into Swedish, we used cognitive interviewing to evaluate test content and the response process, that is, how people make decisions when responding to survey items. Cognitive interviews were conducted with 13 primary health care patients with insomnia disorder (mean age, 49 years; SD 15.5). Iterative, reparative analysis was used to investigate test content. Descriptive deductive analysis was used to investigate interview transcripts for the themes of the cognitive model: comprehension, retrieval, decision process, and judgement. Together, the themes explain the response process when responding to a patient-reported outcome measure. Results The overall comprehension of the CSD could be affected by poor adherence to the instructions (comprehension). Patients had difficulty with recall if they did not complete the diary immediately in the morning and just before bedtime (retrieval). They could have problems deciding how to respond to certain items because they imbued sleep-related concepts with extra meaning (decision process), and had trouble finding response alternatives nuanced enough to describe their experience of sleep and tiredness (judgement). Conclusions This study contributes knowledge on how the instrument is perceived and used by care-seeking patients with insomnia. In this context, the CSD exhibits known flaws such as memory lapses if the diary is not filled in directly in the morning. To increase the accuracy of patients’ responses, therapists should support patients in reading the instructions.

Abstract Common mitochondrial DNA (mtDNA) deletions are large structural variants in the mitochondrial genome that accumulate in metabolically active tissues with age and have been investigated in various diseases. We applied the Splice-Break2 pipeline (designed for high-throughput quantification of mtDNA deletions) to human RNA-Seq datasets and describe the methodological considerations for evaluating common deletions in bulk, single-cell, and spatial transcriptomics datasets. A robust evaluation of 1570 samples from 14 RNA-Seq studies showed: (i) the abundance of some common deletions detected in PCR-amplified mtDNA correlates with levels observed in RNA-Seq data; (ii) RNA-Seq library preparation method has a strong effect on deletion detection; (iii) deletions had a significant, positive correlation with age in brain and muscle; (iv) deletions were enriched in cortical grey matter, specifically in layers 3 and 5; and (v) brain regions with dopaminergic neurons (i.e., substantia nigra, ventral tegmental area, and caudate nucleus) had remarkable enrichment of common mtDNA deletions.