Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission.

Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy). We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia.

Palliative Care Research and Clinical Practice Priorities in the United States as Identified by an Interdisciplinary Modified Delphi Approach.

Background: Palliative care demands in the United States are growing amid a comparatively small workforce of palliative care clinicians and researchers. Therefore, determining research and clinical practice priorities is essential for streamlining initiatives to advance palliative care science and practice. Objectives: To identify and rank palliative care research and clinical practice priority areas through expert consensus. Design: Using a modified Delphi method, U.S. palliative care experts identified and ranked priority areas in palliative care research and clinical practice. Priorities were thematically grouped and analyzed for topic content and frequency; univariate analysis used the median of each priority item ranking, with a cutoff median of ≤8 indicating >76% agreement for an item's ranking. Results: In total, 27 interdisciplinary pediatric and adult palliative care experts representing 19 different academic institutions and medical centers participated in the preliminary survey and the first Delphi round, and 22 participated in the second Delphi round. The preliminary survey generated 78 initial topics, which were developed into 22 priority areas during the consensus meeting. The top five priorities were (1) access to palliative care, (2) equity in palliative care, (3) adequate financing of palliative care, (4) provision of palliative care in primary care settings, and (5) palliative care workforce challenges. Conclusions: These expert-identified priority areas provide guidance for researchers and practitioners to develop innovative models, policies, and interventions, thereby enriching the quality of life for those requiring palliative care services.

Yield of diagnostic testing in evaluating etiology and end organ effects of pediatric hypertension.

BACKGROUND: Current recommendations regarding the utility of diagnostic investigations for pediatric hypertension are based on limited evidence, leading to wide practice variation. The objective of this study was to characterize the cohort of children that may benefit from secondary hypertension workup, and determine the diagnostic yield of investigations. METHODS: This was a single-center, retrospective cohort study of 169 children aged 1-18 years referred between 2000 and 2015, to a tertiary pediatric nephrology center in Canada, for evaluation of hypertension. The number of investigations completed, abnormal findings, and diagnostic findings that helped establish hypertension etiology was determined. RESULTS: 56 children were diagnosed with primary and 72 children with secondary hypertension in the outpatient setting. Secondary hypertension was predominant at all ages except for obese adolescents ≥ 12 years. Half of children with traditional risk factors for primary hypertension, including obesity, were diagnosed with secondary hypertension. Kidney ultrasound had the highest yield of diagnostic results (19.8%), with no difference in yield between age groups (P = 0.19). Lipid profile had a high yield of abnormal results (25.4%) as part of cardiovascular risk assessment but was only abnormal in overweight/obese children. Echocardiogram had a high yield for identification of target-organ effects in hypertensive children (33.3%). CONCLUSION: A simplified secondary hypertension workup should be considered for all hypertensive children and adolescents. High yield investigations include a kidney ultrasound, lipid profile for overweight/obese children, and echocardiograms for assessment of target-organ damage. Further testing could be considered based on results of initial investigations for the most cost-effective management. A higher resolution version of the Graphical abstract is available as Supplementary information.

Testing the somatic marker hypothesis in decisions-from-experience with non-stationary outcome probabilities.

Introduction: The Somatic Marker Hypothesis (SMH) posits that in experience-based choice, people develop physiological reactions that mark options as either positive or negative. These somatic markers aid decision making because they differentiate between "good" and "bad" options during pre-choice deliberation. Methods: We examined this proposed role for somatic states in two decision-from-experience tasks (each N = 36) in which participants selected repeatedly with full feedback (i.e., for obtained and forgone outcomes) between two unlabeled options that returned wins or losses, with half receiving an additional summary of past outcomes. The probabilities of good and bad outcomes changed at an unannounced point. Participants completed a 100-trial game with a switch in the optimal option after trial 40 (Study 1) or a 200-trial game with switch points after trial 40 and trial 120 (Study 2). Skin conductance (SC) was measured continuously as an index of emotional intensity, from which we extracted measures of anticipatory SC (pre-choice) and outcome SC (post-choice). Results: Participants reliably selected the optimal option prior to any switches. They also altered their choices appropriately when the payoffs changed, though optimal play following payoff switches was reduced. Losses resulted in a greater outcome SC than wins, but only in Study 1, as did the finding that the outcome SC was greater when the forgone outcome was positive. Anticipatory SC did not reliably predict optimal play in either study. Discussion: These results provide little support for the SMH. Our studies point to the importance of using diverse tasks and measures and very large sample sizes when testing the role of somatic states in decision making.

Using wearable technology to prevent pressure injuries: An integrative review.

BACKGROUND: Hospital-acquired pressure injuries (HAPIs) are a significant problem for hospitals worldwide, negatively affecting patients and organizations by decreasing quality of life and increasing organizational cost of care and workload. A common pressure injury prevention intervention is frequent turning, though compliance can be low. As a newer technology, wearable sensors have emerged as an intervention to increase turn compliance. AIMS: The aim of this integrative review was to determine the clinical outcomes of using wearable sensors as a HAPI prevention intervention. METHODS: This integrative review was appraised by two independent reviewers using the Johns Hopkins Nursing Evidence-Based Practice Research Appraisal Tool. RESULTS: Eleven articles were included. The use of wearable sensors increases compliance with frequent turn protocols while decreasing HAPIs and reducing organizational costs. Despite this, the use of such technology was not found to increase the quality of turns. Although staff who used this technology reported positive feedback, technological training is needed to ensure proper use of the sensors. LINKING ACTION TO PRACTICE: This innovation has the potential to transform how nursing staff prevent pressure injuries, but more research is needed to definitively state whether wearable sensors will be efficacious as a pressure injury prevention intervention.

Quantitative research on the impact of COVID-19 on frontline nursing staff at a military hospital in Saudi Arabia.

AIM: The aim of the study was to examine the relationship between stress, psychological symptoms and job satisfaction among frontline nursing staff at a military hospital in Saudi Arabia during the COVID-19 pandemic. DESIGN: Descriptive cross-sectional study. METHODS: Data were collected using an online survey. All Registered Nurses (N = 1,225) working at a military hospital between February to April 2021 were contacted, 625 responded (51%). Data were analysed using descriptive and multivariate analysis, Student's t-test for independent samples and one-way analysis of variance followed by Tukey's multiple comparison tests. RESULTS: Stress was experienced more significantly than depression or anxiety. Approximately 29% of the change in scores for psychological symptoms was explained by age group, being a Saudi national and working in emergency departments (F[3,620]  = 19.063, p < 0.0001). A 37% change in nursing stress scores was explained by nationality and work department. (F[5,618]  = 19.754, p < 0.0001). A 29% change in job satisfaction scores was explained by nationality and work department (F[3,620]  = 19.063, p < 0.0001).

Social Norms About Handling Financial Challenges in Relation to Health-Protective Capacity Among Low-Income Older Adults.

BACKGROUND AND OBJECTIVES: Despite evidence linking financial challenges to poor health among older adults, effective interventions are lacking. This study examined the experience of living with financial challenges, useful strategies to handle them, and social norms that may constrain options and decision-making. RESEARCH DESIGN AND METHODS: This two-staged qualitative study recruited low-income older adults from the United States Baltimore City area. First, semistructured individual interviews examined older adults' experiences and strategies used to handle financial challenges. Then, vignette-based focus groups examined relevant social norms. Transcripts were coded, and hierarchical themes were described using thematic analysis. RESULTS: Two themes were generated. First, the social norms relevant to financial challenges share a common underlying assumption of personal responsibility. Second, social norms about personal responsibility are inconsistent with the experiences of older adults facing financial challenges, who typically lack control over their situation and face structural barriers to preventing and handling financial challenges. Differences between statements related to norms and personal responsibility were found across six subthemes, including how finances should be handled to prevent financial challenges, the causes of financial challenges, asking for help from community resources, navigating community resources, getting help from family, and cutting back to handle financial challenges. DISCUSSION AND IMPLICATIONS: The disconnect between social norms and the reality of financial challenges among older adults may explain why so many older adults cut back to the point of foregoing necessities. There is an urgent need to strengthen the social safety net and remove normative barriers to services.

A qualitative descriptive study of effective leadership and leadership development strategies used by nurse leaders in European island countries.

AIM: Nurse leaders influence workplace culture; however, little is known about ethnic cultural influences on nurse leader development. This research aims to identify personal strategies promoting effective leadership by nurse leaders from European small island countries. DESIGN: Descriptive qualitative study. METHODS: In 2017, nineteen semi-structured interviews with nurse leaders from England, Greece, Republic of Ireland and Malta explored leadership journeys, strategies employed to support their growth and development, and how cultural identity played a role. Transcripts were analysed using reflexive thematic analysis. RESULTS: Four main themes and 12 subthemes captured the strategies and approaches of the nurse leaders: (1) Influences, (2) Communication, (3) Process and (4) Relationships. These findings reflect and validate the five transformational leadership practices of the Exemplary Leadership Model. While cultural island identity was discussed, there was a shared cultural identity within the role of "nurse leader" that spanned all islands. PATIENT OR PUBLIC CONTRIBUTIONS: Nineteen nurse leaders contributed to this study.

Considerations of Intersectionality for Older Adults with Palliative Care Needs in the Emergency Department: An Integrative Review.

Purpose of Review: We sought to identify current interventions, research, or non-research evidence that has direct or indirect consideration of intersectionality in the care of older adults in the emergency department (ED). An integrative review informed by Crenshaw's Theory of Intersectionality was conducted in accordance with Whittemore and Knafl's five-stage methodology. A rigorous review process determined appropriateness for inclusion, and articles were analyzed for areas related to direct or indirect relationship to intersectionality. Recent Findings: Older adults aged 60 and above in the United States (US) account for more than 20% of ED visits annually, and half of older adults will visit the ED in their last year of life. There has been a growing focus on adapting the ED to meet the palliative care needs of older adults, but relatively little consideration has been given to older adults' intersectional identities. Summary: Six articles were identified that provided indirect insights into the status of intersectionality in ED-based palliative care for older adults. Two areas of interest were identified: (1) intersectional elements or reference to such elements embedded within the studies; and (2) the challenges of adapting quantitative methodologies to incorporate variables and approaches that would allow for intersectional analysis. This review highlights areas for future research along with recommendations for adopting an intersectional framing into commonly used methodologies.

Antibody specificity against highly conserved membrane protein Claudin 6 driven by single atomic contact point.

The tight junction protein claudin 6 (CLDN6) is differentially expressed on cancer cells with almost no expression in healthy tissue. However, achieving therapeutic MAb specificity for this 4 transmembrane protein is challenging because it is nearly identical to the widely expressed CLDN9, with only 3 extracellular amino acids different. Most other CLDN6 MAbs, including those in clinical development are cross-reactive with CLDN9, and several trials have now been stopped. Here we isolated rare MAbs that bind CLDN6 with up to picomolar affinity and display minimal cross-reactivity with CLDN9, 22 other CLDN family members, or across the human membrane proteome. Amino acid-level epitope mapping distinguished the binding sites of our MAbs from existing clinical-stage MAbs. Atomic-level epitope mapping identified the structural mechanism by which our MAbs differentiate CLDN6 and CLDN9 through steric hindrance at a single molecular contact point, the γ carbon on CLDN6 residue Q156.