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Purpose: Modeling passively collected smartphone sensor data (called digital phenotyping) has the potential to detect distress among family caregivers and patients with advanced cancer and could lead to novel clinical models of cancer care. The purpose of this study was to assess the feasibility and acceptability of collecting passive smartphone data from family caregivers and their care recipients with advanced cancer over 24 weeks., Methods: This was an observational feasibility study. Family caregivers and patients with advanced cancer were recruited through clinic or via social media and downloaded a digital phenotyping application (Beiwe) to their smartphones that passively collected sensor data over 24 weeks. Feasibility was evaluated by quantifying enrollment and retention and the quantity of acquired data. Acceptability was assessed through post-24 week qualitative interviews., Results: Of 178 caregiver and patient dyads approached, 22.5% of caregivers (n = 40) and 10.1% of patients (n = 18) both consented to the study and successfully downloaded the application, with most recruited through social media (93%). Of 24 weeks (168 days), the median number of days that data were received was 141 days. Interviews yielded three themes: (1) experiences with study procedures were generally positive despite some technical challenges; (2) security and privacy concerns were minimal, mitigated by clear explanations, trust in the health care system, and privacy norms; and (3) a clinical model that used passive smartphone monitoring to automatically trigger assistance could be beneficial but with concern about false alarms., Conclusion: This pilot study of collecting passive smartphone data found mixed indicators of feasibility, with suboptimal enrollment rates, particularly via clinic, but positive retention and data collection rates for those who did enroll. Participants had generally positive views of passive monitoring.

Ultrasound elastography provides diagnostic information based on tissue elasticity. There is a lack of specific studies on the application of elastography in canine intestinal assessment. Therefore, we reviewed comparative medicine studies and those referring to the literature listed in the databases. Static and dynamic elastography techniques are widely applied in human intestinal diseases, especially Chron's disease, but few studies have investigated the application of these modalities in canine enteropathies. This case raises questions about the use of new diagnostic imaging techniques in veterinary gastroenterology and highlights the need for further research. Hence, this study aimed to review the literature on the physical principles of elastography and its clinical application in the intestinal evaluation of dogs., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Oliveira, et al.)

Enteropathies are prevalent in dog internal medicine, and their diagnosis involves a lengthy process. One of the tests requested is for biomarkers, which are important as they can provide data on intestinal functionality, intensity of inflammation, and response to treatment, and can help determine the prognosis. This study aimed to conduct a literature review on the main serum and fecal intestinal biomarkers in dogs and proposed to refine the correlations between these indicators and enteropathies. It was observed that the main biomarkers used in the intestinal evaluation of dogs were alpha 1-proteinase inhibitory factor, immunoglobulin A, methylmalonic acid, serum folate, serum cobalamin, C-reactive protein, fecal and serum calprotectin, and dysbiosis index. However, we suggest that more research be carried out to clarify the relationship between enteropathies and intestinal biomarkers. We noticed a lack of studies on specific intestinal markers and indicator variables in healthy dogs and those with various enteropathies; moreover, no data are available on the association of these laboratory parameters., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Iago Martins Oliveira et al.)

Background: In the second half of 2023 the Senate for Science, Health and Nursing of Berlin commissioned an explicit gerontological expert report from the team of authors, which was intended to provide suggestions for the modernization and concretization of § 71 of the German Social Code Act (SGB) XII, i.e., the central social law basis for so-called care of older people. It was completed by the end of 2023. The objective of the report was to provide suggestions for a Berlin Assistance for Old People Structural Law that considers the differentiation and diversity of the life phase of old age by identifying, analyzing and describing the necessary individual services., Aim of the Article: The approach and the central results of the report are presented and discussed., Material and Methods: In a multistep procedure, combined with a multimodal research approach, various methods were combined in order to generate a comprehensive understanding of the current situation of so-called assistance for older people and gerontological justifications for its services. Critical and selective literature reviews, document analysis and qualitative guideline-based expert interviews were used., Results and Discussion: The expert report contains concrete recommendations for an age phase and life situation-orientated development of individual services according to § 71 SGB XII. This relates to approaches, forms and topics of counselling that enable and support successful ageing for all older people. The report also explicitly identifies objects of necessary cash and non-cash benefits, which, even in precarious situations in old age, aim to strengthen the ability for self-help and provide the opportunity to participate independently in community life., (© 2024. The Author(s).)

Background: Iron Deficiency (ID) affects two billion people worldwide, predominantly adolescent girls, and may be associated with increased psychopathology. The associations between ID and symptoms of depression and anxiety in adolescents were examined using data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of non-institutionalized Americans., Methods: The current analysis included survey cycles where both iron-related markers and mental health-related outcomes were collected in adolescents 12 to 17 years old. Acute and serious medical conditions, acute inflammation, and abnormal birth weight led to exclusion. Linear multivariable regression analyses examined the association between ID status (defined based on the total body iron model) and (1) total Patient Health Questionnaire (PHQ-9) score, (2) one item examining anxiety severity, and (3) one item examining overall mental well-being. Covariates included age, sex, race and ethnicity, body mass index, household income, head-of-household marital status, and psychotropic medication use. Sensitivity analyses examined the robustness of the findings when ID was defined based on the ferritin model., Results: In 1990 adolescents (age [mean ± SD]: 14.5 ± 1.7 years; 85.7% females), ID with and without anemia was significantly associated with a higher PHQ-9 score in multiracial adolescents (Cohen's d = 1.09, p = 0.0005 for ID without anemia; d = 0.92, p = 0.0395 for ID with anemia). Moreover, ID with anemia was associated with more severe anxiety (d = 3.00, p = 0.0130) and worse mental well-being (d = 2.75, p = 0.0059) in multiracial adolescents. The findings remained significant after adjusting for psychotropic use and in the sensitivity analyses., Conclusions: Iron deficiency is associated with poorer mental health in adolescents of multiracial background. Future studies should confirm these findings prospectively and examine the underlying mechanism.

Pluripotent mouse embryonic stem cells (ESCs) can differentiate to all germ layers and serve as an in vitro model of embryonic development. To better understand the differentiation paths traversed by ESCs committing to different lineages, we track individual differentiating ESCs by timelapse imaging followed by multiplexed high-dimensional Imaging Mass Cytometry (IMC) protein quantification. This links continuous live single-cell molecular NANOG and cellular dynamics quantification over 5-6 generations to protein expression of 37 different molecular regulators in the same single cells at the observation endpoints. Using this unique data set including kinship history and live lineage marker detection, we show that NANOG downregulation occurs generations prior to, but is not sufficient for neuroectoderm marker Sox1 upregulation. We identify a developmental cell type co-expressing both the canonical Sox1 neuroectoderm and FoxA2 endoderm markers in vitro and confirm the presence of such a population in the post-implantation embryo. RNASeq reveals cells co-expressing SOX1 and FOXA2 to have a unique cell state characterized by expression of both endoderm as well as neuroectoderm genes suggesting lineage potential towards both germ layers., (© 2024. The Author(s).)

Despite advances in treatment, lung cancer survival rates remain low. A better understanding of the cellular heterogeneity and interplay of cancer-associated fibroblasts (CAFs) within the tumor microenvironment will support the development of personalized therapies. We report a spatially resolved single-cell imaging mass cytometry (IMC) analysis of CAFs in a non-small cell lung cancer cohort of 1,070 patients. We identify four prognostic patient groups based on 11 CAF phenotypes with distinct spatial distributions and show that CAFs are independent prognostic factors for patient survival. The presence of tumor-like CAFs is strongly correlated with poor prognosis. In contrast, inflammatory CAFs and interferon-response CAFs are associated with inflamed tumor microenvironments and higher patient survival. High density of matrix CAFs is correlated with low immune infiltration and is negatively correlated with patient survival. In summary, our data identify phenotypic and spatial features of CAFs that are associated with patient outcome in NSCLC., Competing Interests: Declaration of interests B.B. has co-founded Navignostics, a spin-off company of the University of Zurich, and is one of its shareholders and a board member., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The approach of socio-technical systems (STS) for a successful life in old age focuses on the combination of technical and sociocultural factors in one. Technological systems have long since ceased to be limited to simple functions; instead, they enable customizable applications, interactive use combined with complex communication and action strands. The associated interactions with the technical system suggest a perspective on interactions and relationships., Objective: Research results show that individualizable functions of STSs are rated positively in terms of acceptance and use by older people. From a geragogical perspective, questions arise regarding the appropriation of older people and the design of learning processes (socio-technical learning arrangements)., Material and Methods: A relational view of learning and educational processes relating to the appropriation and acquisition of competences for designing and using STS in real-world situations is developed based on a formative qualitative research design of the "RUBYDemenz" project. In particular, data/results from interviews with voluntary learning facilitators, professional practice facilitators, focus groups and research workshops are utilized., Results and Discussion: Empirical findings can be used to develop starting points for educational and learning processes to expand competences in the context of technology use. Approaches to education, training and further training follow on from this as does the question of whether the research/development process itself must be designed as a learning process in which all participants are involved as learners, with the aim of achieving the best possible fit between the technical solutions and the intended areas of application in real-world situations., (© 2024. The Author(s).)

As noncontact health interventions have become critical during the Covid-19 pandemic, our study aimed to systematically review the published literature for barriers and facilitators influencing the adoption and use of remote health intervention and technology, as perceived by adult patients with diabetes or cardiovascular diseases (CVD) belonging to groups that are socially/economically marginalized and/or medically under-resourced. We searched Medline, Embase, CINAHL, and PsychINFO for peer-reviewed articles published from 2010 to 2018. We employed content analysis to analyze qualitative patient feedback from the included studies. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 42 studies met the inclusion criteria. The design of the remote health technology used was the most frequently mentioned facilitator and barrier to remote health technology adoption and use. Our results should draw the attention of technology developers to the usability and feasibility of remote technology among populations that are socially/economically marginalized and/or medically under-resourced., (©2022 AMIA - All rights reserved.)

This article reviews the role of iron in brain development and function, with a focus on the association between iron deficiency (ID) and neuropsychiatric conditions. First, we describe how ID is defined and diagnosed. Second, the role of iron in brain development and function is summarized. Third, we review current findings implicating ID in a number of neuropsychiatric conditions in children and adolescents, including attention deficit hyperactivity disorder and other disruptive behavior disorders, depressive and anxiety disorders, autism spectrum disorder, movement disorders, and other situations relevant to mental health providers. Last, we discuss the impact of psychotropic medication on iron homeostasis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cultivated meat (CM) technology has the potential to disrupt the food industry-indeed, it is already an inevitable reality. This new technology is an alternative to solve the environmental, health and ethical issues associated with the demand for meat products. The global market longs for biotechnological improvements for the CM production chain. CM, also known as cultured, cell-based, lab-grown, in vitro or clean meat, is obtained through cellular agriculture, which is based on applying tissue engineering principles. In practice, it is first necessary to choose the best cell source and type, and then to furnish the necessary nutrients, growth factors and signalling molecules via cultivation media. This procedure occurs in a controlled environment that provides the surfaces necessary for anchor-dependent cells and offers microcarriers and scaffolds that favour the three-dimensional (3D) organisation of multiple cell types. In this review, we discuss relevant information to CM production, including the cultivation process, cell sources, medium requirements, the main obstacles to CM production (consumer acceptance, scalability, safety and reproducibility), the technological aspects of 3D models (biomaterials, microcarriers and scaffolds) and assembly methods (cell layering, spinning and 3D bioprinting). We also provide an outlook on the global CM market. Our review brings a broad overview of the CM field, providing an update for everyone interested in the topic, which is especially important because CM is a multidisciplinary technology.

Recent advances in multiplexed imaging methods allow simultaneous detection of dozens of proteins and hundreds of RNAs, enabling deep spatial characterization of both healthy and diseased tissues. Parameters for the design of optimal multiplex imaging studies, especially those estimating how much area has to be imaged to capture all cell phenotype clusters, are lacking. Here, using a spatial transcriptomic atlas of healthy and tumor human tissues, we developed a statistical framework that determines the number and area of fields of view necessary to accurately identify all cell phenotypes that are part of a tissue. Using this strategy on imaging mass cytometry data, we identified a measurement of tissue spatial segregation that enables optimal experimental design. This strategy will enable an improved design of multiplexed imaging studies., (© 2022. The Author(s).)

Intermittent fasting (IF) is an increasingly popular diet involving short-term fasting and/or caloric restriction. While published research highlights physiological effects (e.g., weight, body fat) of IF, hardly any research has examined its associations with psychological factors. This study aimed to investigate the relationship between IF and binge eating, impulsivity, intuitive eating, and mindful eating. An undergraduate sample (N = 298) was recruited through a large southwestern university psychology subject pool. The sample was divided into three groups based on IF status: Current IF (n = 70), Past IF (n = 48), and No IF (n = 182). Current IF was negatively associated with lack of perseverance (e.g., "I generally like to see things through to the end"; p < .01) and intuitive eating (p < .05), varying by subscale, compared to the other groups. Notably, Past-IF, but not Current IF, participants were more likely to binge eat than individuals who reported never fasting (p = .03). These findings add credence to the rapidly developing area of research suggesting IF is associated with increased disordered eating behaviors. Notably, the findings from this study are limited due to the lack of diversity sample, such that generalizations can only be made toward White, middle-to-high income, college students. Future longitudinal studies are needed to test the directionality of these relationships., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Palliative care trial recruitment of African Americans (AAs) is a formidable research challenge., Objectives: Examine AA clinical trial recruitment and enrollment in a palliative care randomized controlled trial (RCT) for heart failure (HF) patients and compare patient baseline characteristics to other HF palliative care RCTs., Methods: This is a descriptive analysis the ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends: Comprehensive Heartcare for Patients and Caregivers) RCT using bivariate statistics to compare racial and patient characteristics and differences through recruitment stages. We then compared the baseline sample characteristics among three palliative HF trials., Results: Of 785 patients screened, 566 eligible patients with NYHA classification III-IV were approached; 461 were enrolled and 415 randomized (AA = 226). African Americans were more likely to consent than Caucasians (55%; P FDR = .001), were younger (62.7 + 8; P FDR = .03), had a lower ejection fraction (39.1 + 15.4; P FDR = .03), were more likely to be single ( P FDR = .001), and lack an advanced directive (16.4%; P FDR < .001). AAs reported higher goal setting (3.3 + 1.3; P FDR = .007), care coordination (2.8 + 1.3; P FDR = .001) and used more "denial" coping strategies (0.8 + 1; P FDR = .001). Compared to two recent HF RCTs, the ENABLE CHF-PC sample had a higher proportion of AAs and higher baseline KCCQ clinical summary scores., Conclusion: ENABLE CHF-PC has the highest reported recruitment rate and proportion of AAs in a palliative clinical trial to date. Community-based recruitment partnerships, recruiter training, ongoing communication with recruiters and clinician co-investigators, and recruiter racial concordance likely contributed to successful recruitment of AAs. These important insights provide guidance for design of future HF palliative RCTs., Trial Registration: ClinicalTrials.gov Identifier: NCT02505425.

Background: Family caregivers play a vital, yet stressful role in managing the healthcare needs and optimizing the quality of life of patients with advanced cancer, from the time they are newly diagnosed until end of life. While early telehealth palliative care has been found to effectively support family caregivers, little work has focused on historically under-resourced populations, particularly African American and rural-dwelling individuals. To address this need, we developed and are currently testing Project ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone, a lay navigator-led, early palliative care coaching intervention for family caregivers of African American and rural-dwelling patients with newly diagnosed advanced cancer., Methods: This is a 2-site, single-blind, hybrid type I implementation-effectiveness trial of the Cornerstone intervention versus usual care. Cornerstone is a multicomponent intervention based on Pearlin's Stress-Health Process Model where African American and/or rural-dwelling family caregivers of patients with newly diagnosed advanced cancer (target sample size = 294 dyads) are paired with a lay navigator coach and receive a series of six, brief 20-60-min telehealth sessions focused on stress management and coping, caregiving skills, getting help, self-care, and preparing for the future/advance care planning. Subsequent to core sessions, caregivers receive monthly follow-up indefinitely until the patient's death. Caregiver and patient outcomes are collected at baseline and every 12 weeks until the patient's death (primary outcome: caregiver distress at 24 weeks; secondary outcomes: caregiver: quality of life and burden; patient: distress, quality of life, and healthcare utilization). Implementation costs and the intervention cost effectiveness are also being evaluated., Discussion: Should this intervention demonstrate efficacy, it would yield an implementation-ready model of early palliative care support for under-resourced family caregivers. A key design principle that has centrally informed the Cornerstone intervention is that every caregiving situation is unique and each caregiver faces distinct challenges that cannot be addressed using a one-size-fits all approach. Hence, Cornerstone employs culturally savvy lay navigator coaches who are trained to establish a strong, therapeutic alliance with participants and tailor their coaching to a diverse range of individual circumstances., Trial Registration: ClinicalTrials.gov NCT04318886 . Registered on 20 March, 2020., (© 2022. The Author(s).)

Background: The objective of this study was to assess the feasibility, acceptability, and potential efficacy of ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone-a lay navigator-led, early palliative care telehealth intervention for African American/Black and/or rural-dwelling family caregivers of individuals with advanced cancer (ClinicalTrials.gov identifier NCT03464188)., Methods: This was a pilot randomized trial (November 2019 to March 2021). Family caregivers of patients with newly diagnosed, stage III/IV, solid-tumor cancers were randomized to receive either an intervention or usual care. Intervention caregivers were paired with a specially trained lay navigator who delivered 6 weekly, 20-minute to 60-minute telehealth coaching sessions plus monthly follow-up for 24 weeks, reviewing skills in stress management, self-care, getting help, staying organized, and future planning. Feasibility was assessed according to the completion of sessions and questionnaires (predefined as a completion rate ≥80%). Acceptability was determined through intervention participants' ratings of their likelihood of recommending the intervention. Measures of caregiver distress and quality of life were collected at 8 and 24 weeks., Results: Sixty-three family caregivers were randomized (usual care, n = 32; intervention, n = 31). Caregivers completed 65% of intervention sessions and 87% of questionnaires. Average ratings for recommending the program were 9.4, from 1 (not at all likely) to 10 (extremely likely). Over 24 weeks, the mean ± SE Hospital Anxiety and Depression Scale score improved by 0.30 ± 1.44 points in the intervention group and worsened by 1.99 ± 1.39 points in the usual care group (difference, -2.29; Cohen d, -0.32). The mean between-group difference scores in caregiver quality of life was -1.56 (usual care - intervention; d, -0.07). Similar outcome results were observed for patient participants., Conclusions: The authors piloted ENABLE Cornerstone, an intervention for African American and rural-dwelling advanced cancer family caregivers. The acceptability of the intervention and data collection rates were high, and the preliminary efficacy for caregiver distress was promising., Lay Summary: To date, very few programs have been developed to support under-resourced cancer family caregivers. To address this need, the authors successfully pilot tested an early palliative care program, called Educate, Nurture, Advise, Before Life Ends (ENABLE) Cornerstone, for African American and rural family caregivers of individuals with advanced cancer. Cornerstone is led by specially trained lay people and involves a series of weekly phone sessions focused on coaching caregivers to manage stress and provide effective support to patients with cancer. The authors are now testing Cornerstone in a larger trial. If the program demonstrates benefit, it may yield a model of caregiver support that could be widely implemented., (© 2021 American Cancer Society.)

The suppression of spontaneous otoacoustic emissions (SOAEs) allows the objective evaluation of cochlear frequency selectivity by determining the suppression tuning curve (STC). Interestingly, some STCs have additional sidelobes at the high frequency flank, which are thought to result from interaction between the probe tone and the cochlear standing wave corresponding to the SOAE being suppressed. Sidelobes are often in regions of other neighboring SOAEs but can also occur in the absence of any other SOAE. The aim of this study was to compare STCs and psychoacoustic tuning curves (PTCs). Therefore, STCs and PTCs were measured in: (1) subjects in which the STC had a sidelobe, and (2) subjects without STC sidelobes. Additionally, PTCs were measured in subjects without SOAEs. Across participant groups, the quality factor Q 10dB of the PTCs was similar, independently from whether SOAEs were present or absent. Thus, the presence of an SOAE does not provide enhanced frequency selectivity at the emission frequency. Moreover, both PTC and STC show irregularities, but these are not related in a straightforward way. This suggests that different mechanisms cause these irregularities.

Context: Patients with advanced cancer often involve family caregivers in health-related decision-making from diagnosis to end-of-life; however, few interventions have been developed to enhance caregiver decision support skills., Objectives: Assess the feasibility, acceptability, and potential efficacy of individual intervention components of CASCADE (CAre Supporters Coached to be Adept DEcision Partners), an early telehealth, palliative care coach-led decision support training intervention for caregivers., Methods: Pilot factorial trial using the multiphase optimization strategy (October 2019-October 2020). Family caregivers and their care recipients with newly-diagnosed advanced cancer (n = 46 dyads) were randomized to1 of 8 experimental conditions that included a combination of one of the following three CASCADE components: 1) effective decision support psychoeducation; 2) decision support communication training; and 3) Ottawa Decision Guide training. Feasibility was assessed by completion of sessions and questionnaires (predefined as ≥80%). Acceptability was determined through postintervention interviews and participants' ratings of their likelihood to recommend. Measures of effective decision support and caregiver and patient distress were collected at Twelve and Twenty four weeks., Results: Caregiver participants completed 78% of intervention sessions and 81% of questionnaires; patients completed 80% of questionnaires. Across conditions, average caregiver ratings for recommending the program to others was 9.9 on a scale from 1-Not at all likely to 10-Extremely likely. Individual CASCADE components were observed to have potential benefit for effective decision support and caregiver distress., Conclusion: We successfully piloted a factorial trial design to examine components of a novel intervention to enhance the decision support skills of advanced cancer family caregivers. A fully-powered factorial trial is warranted., Key Message: We pilot tested components of CASCADE, an early palliative care decision support training intervention for family caregivers of patients with advanced cancer. CASCADE components were acceptable and the trial design feasible, providing promising future directions for palliative care intervention development and testing. Pilot results will inform a fully-powered trial., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

While the efficacy of Internet- and mobile-based interventions (IMIs) for treating anxiety disorders is well established, there is no comprehensive overview about the underlying therapeutic processes so far. Thus, this systematic review and meta-analysis evaluated research on mediators and mechanisms of change in IMIs for adult anxiety disorders (PROSPERO: CRD42020185545). A systematic literature search was performed in five databases (i.e., CENTRAL, Embase, MEDLINE, PsycINFO and ClinicalTrials.gov). Two reviewers independently screened studies for inclusion, assessed the risk of bias and adherence to quality criteria for process research. Overall, 26 studies (N = 6042) investigating 64 mediators were included. Samples consisted predominantly of participants with clinically relevant symptoms of generalized anxiety disorder and severe health anxiety, as well as of participants with non-clinically relevant anxiety symptoms. The largest group of examined mediators (45%) were cognitive variables, evincing also the second highest proportion of significance (19/29); followed in numbers by skills (examined: 22%; significant: 10/14) and a wide range of other (19%; 7/12), emotional/affective (11%; 2/7) and behavioral mediators (3%; 1/2). Meta-analytical synthesis of mediators, limited by a small number of eligible studies, was conducted by deploying a two-stage structural equation modeling approach, resulting in a significant indirect effect for negative thinking (k = 3 studies) and non-significant indirect effects for combined cognitive variables, both in clinical (k = 5) and non-clinical samples (k = 3). The findings of this review might further the understanding on presumed change mechanisms in IMIs for anxiety, informing intervention development and the concurrent optimization of outcomes. Furthermore, by reviewing eligible mediation studies, we discuss methodological implications and recommendations for future process research, striving for causally robust findings. Future studies should investigate a broader range of variables as potential mediators, as well as to develop and apply original (digital) process and engagement measures to gather qualitative and high-resolution data on therapeutic processes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Digital health interventions (DHIs) are efficacious for several mental disorders in youth; however, integrated, evidence-based knowledge about the mechanisms of change in these interventions is lacking., Objective: This systematic review aims to comprehensively evaluate studies on mediators and mechanisms of change in different DHIs for common mental disorders in children and adolescents., Methods: A systematic literature search of the electronic databases Cochrane Central Register of Controlled Trials, Embase, MEDLINE, and PsycINFO was conducted, complemented by backward and forward searches. Two independent reviewers selected studies for inclusion, extracted the data, and rated the methodological quality of eligible studies (ie, risk of bias and 8 quality criteria for process research)., Results: A total of 25 studies that have evaluated 39 potential mediators were included in this review. Cognitive mediators were the largest group of examined intervening variables, followed by a broad range of emotional and affective, interpersonal, parenting behavior, and other mediators. The mediator categories with the highest percentages of significant intervening variables were the groups of affective mediators (4/4, 100%) and combined cognitive mediators (13/19, 68%). Although more than three-quarters of the eligible studies met 5 or more quality criteria, causal conclusions have been widely precluded., Conclusions: The findings of this review might guide the empirically informed advancement of DHIs, contributing to improved intervention outcomes, and the discussion of methodological recommendations for process research might facilitate mediation studies with more pertinent designs, allowing for conclusions with higher causal certainty in the future., (©Matthias Domhardt, Sophie Engler, Hannah Nowak, Arne Lutsch, Amit Baumel, Harald Baumeister. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.11.2021.)

Objective: Resilience has been proposed as a primary factor in how many family caregivers of patients with advanced cancer are able to resist psychological strain and perform effectively in the role while bearing a high load of caregiving tasks. To evaluate this hypothesis, we examined whether self-perceived resilience is associated with distress (anxiety and depressive symptoms), caregiver preparedness, and readiness for surrogate decision-making among a racially diverse sample of family caregivers of patients with newly diagnosed advanced cancer., Methods: Secondary analysis of baseline data from two small-scale, pilot clinical trials that both recruited family caregivers of patients with newly diagnosed advanced cancer. Using multivariable linear regression, we analyzed relationships of resilience as a predictor of mood, caregiving preparedness, and readiness for surrogate decision-making, controlling for sociodemographics., Results: Caregiver participants (N = 112) were mean 56 years of age and mostly female (76%), the patient's spouse/partner (52%), and White (56%) or African-American/Black (43%). After controlling for demographics, standardized results indicated that higher resilience was relevantly associated with higher caregiver preparedness (beta = .46, p < .001), higher readiness for surrogate decision-making (beta = .20, p < .05) and lower anxiety (beta =  - .19, p < .05), and depressive symptoms (beta =  - .20, p < .05)., Conclusions: These results suggest that resilience may be critical to caregivers' abilities to manage stress, be effective sources of support to patients, and feel ready to make future medical decisions on behalf of patients. Future work should explore and clinicians should consider whether resilience can be enhanced in cancer caregivers to optimize their well-being and ability to perform in the caregiving and surrogate decision-making roles., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The access to empirically-supported treatments for common mental disorders in children and adolescents is often limited. Mental health apps might extend service supplies, as they are deemed to be cost-efficient, scalable and appealing for youth. However, little is known about the quality of available apps. Therefore, we aimed to systematically evaluate current mobile-based interventions for pediatric anxiety, depression and posttraumatic stress disorder (PTSD)., Methods: Systematic searches were conducted in Google Play Store and Apple App Store to identify relevant apps. To be eligible for inclusion, apps needed to be: (1) designed to target either anxiety, depression or PTSD in youth (0-18 years); (2) developed for children, adolescents or caregivers; (3) provided in English or German; (4) operative after download. The quality of eligible apps was assessed with two standardized rating systems (i.e., Mobile App Rating Scale (MARS) and ENLIGHT) independently by two reviewers., Results: Overall, the searches revealed 3806 apps, with 15 mental health apps (0.39%) fulfilling our inclusion criteria. The mean overall scores suggested a moderate app quality (MARS: M = 3.59, SD = 0.50; ENLIGHT: M = 3.22, SD = 0.73). Moreover, only one app was evaluated in an RCT. The correlation of both rating scales was high (r = .936; p < .001), whereas no significant correlations were found between rating scales and user ratings (p > .05)., Conclusions: Our results point to a rather poor overall app quality, and indicate an absence of scientific-driven development and lack of methodologically sound evaluation of apps. Thus, future high-quality research is required, both in terms of theoretically informed intervention development and assessment of mental health apps in RCTs. Furthermore, institutionalized best-practices that provide central information on different aspects of apps (e.g., effectiveness, safety, and data security) for patients, caregivers, stakeholders and mental health professionals are urgently needed., (© 2021. The Author(s).)

Context: Research priority guidelines highlight the need for examining the "dose" components of palliative care (PC) interventions, such as intervention adherence and completion rates, that contribute to optimal outcomes., Objectives: Examine the "dose" effect of PC intervention completion vs. noncompletion on quality of life (QoL) and healthcare use in patients with advanced heart failure (HF) over 32 weeks., Methods: Secondary analysis of the ENABLE CHF-PC intervention trial for patients with New York Heart Association (NYHA) Class III/IV HF. "Completers" defined as completing a single, in-person outpatient palliative care consultation (OPCC) plus 6 weekly, PC nurse coach-led telehealth sessions. "Non-completers" were defined as either not attending the OPCC or completing <6 telehealth sessions. Outcome variables were QoL and healthcare resource use (hospital days; emergency department visits). Mixed models were used to model dose effects for "completers" vs "noncompleters" over 32 weeks., Results: Of 208 intervention group participants, 81 (38.9%) were classified as "completers" with a mean age of 64.6 years; 72.8% were urban-dwelling; 92.5% had NYHA Class III HF. 'Completers' vs. "non-completers"" groups were well-balanced at baseline; however "noncompleters" did report higher anxiety (6.0 vs 7.0, P < 0.05, d = 0.28). Moderate, clinically significant, improved QoL differences were found at 16 weeks in "completers" vs. "non-completers" (between-group difference: -9.71 (3.18), d = 0.47, P = 0.002) but not healthcare use., Conclusion: Higher intervention completion rates of an early PC intervention was associated with QoL improvements in patients with advanced HF. Future work should focus on identifying the most efficacious "dose" of intervention components and increasing adherence to them., Trial Registration: ClinicalTrials.gov Identifier: NCT02505425., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Type 1 diabetes (T1D) has a multifactorial autoimmune etiology, involving environmental prompts and polygenic predisposition. We hypothesized that pancreata from individuals with and at risk for T1D would exhibit dysregulated expression of genes associated with monogenic forms of diabetes caused by nonredundant single-gene mutations. Using a "monogenetic transcriptomic strategy," we measured the expression of these genes in human T1D, autoantibody-positive (autoantibody+), and control pancreas tissues with real-time quantitative PCR in accordance with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. Gene and protein expression was visualized in situ with use of immunofluorescence, RNAscope, and confocal microscopy. Two dozen monogenic diabetes genes showed altered expression in human pancreata from individuals with T1D versus unaffected control subjects. Six of these genes also saw dysregulation in pancreata from autoantibody+ individuals at increased risk for T1D. As a subset of these genes are related to cellular stress responses, we measured integrated stress response (ISR) genes and identified 20 with altered expression in T1D pancreata, including three of the four eIF2α-dependent kinases. Equally intriguing, we observed significant repression of the three arms of the ISR in autoantibody+ pancreata. Collectively, these efforts suggest monogenic diabetes and ISR genes are dysregulated early in the T1D disease process and likely contribute to the disorder's pathogenesis., (© 2021 by the American Diabetes Association.)

Recent systematic reviews and meta-analyses have reported positive benefit of multicomponent "bundled" palliative care interventions for patients and family caregivers while highlighting limitations in determining key elements and mechanisms of improvement. Traditional research approaches, such as the randomized controlled trial (RCT), typically treat interventions as "bundled" treatment packages, making it difficult to assess definitively which aspects of an intervention can be reduced or replaced or whether there are synergistic or antagonistic interactions between intervention components. Progressing toward palliative care interventions that are effective, efficient, and scalable will require new strategies and novel approaches. One such approach is the Multiphase Optimization Strategy (MOST), a framework informed by engineering principles, that uses a systematic process to empirically identify an intervention comprised of components that positively contribute to desired outcomes under real-life constraints. This article provides a brief overview and application of MOST and factorial trial design in palliative care research, including our insights from conducting a pilot factorial trial of an early palliative care intervention to enhance the decision support skills of advanced cancer family caregivers (Project CASCADE)., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The application and integration of molecular profiling technologies create novel opportunities for personalized medicine. Here, we introduce the Tumor Profiler Study, an observational trial combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making with an exploratory approach to improve the biological understanding of the disease., Competing Interests: Declaration of Interests B.S. is scientific co-founder and shareholder of Allcyte GmbH. L.P. and G.G. are listed as inventor on patents related to the 4i technology (WO 2019/207004; WO 2020/008071). G.R., K.-V.L., and S.G.S. are listed on a patent application related to single-cell analyses (European Patent Application No. 20170724.7). H.M. is on advisory boards for Bayer, Astra Zeneca, Janssen, Roche, and Merck. R.D. reports intermittent, project-focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, and Alligator outside the submitted work. G.R. is cofounder and on the Scientific Advisory Board of Computomics GmbH. M.P.L. is a co-founder and shareholder of Oncobit AG and receives research funding from Novartis, Roche, and Molecular Partners. The Tumor Profiler study is jointly funded by a public-private partnership involving F. Hoffmann-La Roche Ltd., ETH Zurich, University of Zurich, University Hospital Zurich, and University Hospital Basel., (Copyright © 2021. Published by Elsevier Inc.)

Background: Nearly 3 million U.S. family caregivers support someone with cancer. However, oncology clinic-based service lines that proactively screen, assess, and support cancer caregivers are nearly nonexistent. Objective: To examine first-year experiences of a nurse-led clinic-based telehealth support service (FamilyStrong) for family caregivers of patients with recently diagnosed grade IV brain tumors. Methods: This is a retrospective evaluation of operational outcomes from initial implementation of the FamilyStrong Service, developed in partnership with Caregiver and Bereavement Support Services at the University of Alabama at Birmingham (UAB) and the UAB Center for Palliative and Supportive Care. From August 2018 to December 2019, 53 family caregivers were proactively identified and enrolled by a palliative care nurse, working approximately one day/week, who performed monthly caregiver distress thermometer screenings by phone and provided emotional, educational, problem-solving, and referral support. Results: Enrolled family caregivers were a mean age of 53.5 years and mostly female (62.3%), full- or part-time employed (67.9%), and the patient's spouse/partner (79.3%). Caregivers provided support 6.7 days/week for 11.2 hours/day. The palliative care nurse performed 235 distress screenings and provided support that included 68 documented instances of emotional, problem-solving, and educational support, 41 nurse-facilitated communications with the neuro-oncology team about patient issues, and 24 referrals to UAB and community services (e.g., counseling). The most common problems caregivers wanted assistance with included: managing their relative's health condition and symptoms (51%), coordinating care/services (21%), and planning for the future/advance care planning (17%). Discussion: The FamilyStrong Program is among the first "real world" oncology clinic-based formal support services for advance cancer family caregivers.

Three-dimensional skin models, also named 3D skin models, human skin equivalents (HSEs), or Human Epidermal Equivalents (HEEs), have been increasingly used for chemical assessments in terms of efficacy and safety. Considering this, we developed an HEE model using immortalized HaCaT cells, aiming to overcome the limitation of primary tissue source. Our 3D model (HaCaT-HEE) exhibited important markers of cell differentiation (CK10, CK14, involucrin, and filaggrin), although the stratum corneum was shown to be modest. Besides, the model showed a good prediction potential considering membrane permeability, sensitivity, specificity, and accuracy in distinguishing irritant and corrosive effects after exposure to selected chemicals recommended by the OECD protocols. We also validated the formazan determination for the MTT method using High-Performance Liquid Chromatography (HPLC). For that, we considered carry over, linearity, reproducibility/robustness, accuracy, precision, selectivity, and matrix effect, according to the Food and Drug Administration (FDA) guideline. Based on our results, we can conclude that our model has an acceptable predictive value for the safety evaluation of compounds after skin exposure, with the great advantage of being constructed using immortalized cells., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Native acquisition of a tonal language (TL) is related to enhanced abilities of pitch perception and production, compared to non-tonal language (NTL) native speakers. Moreover, differences in brain responses to both linguistically relevant and non-relevant pitch changes have been described in TL native speakers. It is so far unclear to which extent differences are present at the peripheral processing level of the cochlea. To determine possible differences in cochlear frequency selectivity between Asian TL speakers and Caucasian NTL speakers, suppression tuning curves (STCs) of spontaneous otoacoustic emissions (SOAEs) were examined in both groups. By presenting pure tones, SOAE levels were suppressed and STCs were derived. SOAEs with center frequencies higher than 4.5 kHz were recorded only in female TL native speakers, which correlated with better high-frequency tone detection thresholds. The suppression thresholds at the tip of the STC and filter quality coefficient Q 10dB did not differ significantly between both language groups. Thus, the characteristics of the STCs of SOAEs do not support the presence of differences in peripheral auditory processing between TL and NTL native speakers., (Copyright © 2020. Published by Elsevier B.V.)

Skin model cultivation under static conditions limits the observation of the toxicity to this single organ. Biology-inspired microphysiological systems associating skin with a liver in the same circulating medium provide a more comprehensive insight into systemic substance toxicity; however, its advantages or limitations for topical substance toxicity remain unknown. Herein, we performed topical (OECD test guideline no. 439) and systemic administration of terbinafine in reconstructed human skin (RHS) vs. a RHS plus liver model cultured in TissUse' HUMIMIC Chip2 (Chip2). Aiming for a more detailed insight into the cutaneous substance irritancy/toxicity, we assessed more than the MTT cell viability: lactate dehydrogenase (LDH), lactate and glucose levels, as well as inherent gene expressions. Sodium dodecyl sulfate (SDS) was the topical irritant positive control. We confirmed SDS irritancy in both static RHS and Chip2 culture by the damage in the morphology, reduction in the lactate production and lower glucose consumption. In the static RHS, the SDS-treated tissues also released significantly high LDH (82%; p < 0.05) and significantly lower IL-6 release (p < 0.05), corroborating with the other metabolic levels. In both static RHS and Chip2 conditions, we confirmed absence of irritancy or systemic toxicity by LDH, glucose or lactate levels for topical 1% and 5% terbinafine and systemic 0.1% terbinafine treatment. However, topical 5% terbinafine treatment in the Chip2 upregulated IL-1α in the RHS, unbalanced apoptotic and proliferative cell ratios in the liver and significantly increased its expression of CYP1A2 and 3A4 enzymes (p < 0.05), proving that it has passed the RHS barrier promoting a liver impact. Systemic 0.1% terbinafine treatment in the Chip2 increased RHS expression of EGFR, increased apoptotic cells in the liver, downregulated liver albumin expression and upregulated CYP2C9 significantly (p < 0.05), acting as an effective hepatotoxic terbinafine control. The combination of the RHS and liver model in the Chip2 allowed a more sensitive assessment of skin and hepatic effects caused by chemicals able to pass the skin (5% terbinafine and SDS) and after systemic 0.1% terbinafine application. The present study opens up a more complex approach based on the microphysiological system to assess more than a skin irritation process., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The use of 3D models in various scientific applications is becoming more popular to replace traditional monolayers models. In this work, we used a three-dimensional in-house model of epidermis using HaCaT immortalized cells to evaluate the dermal toxicity induced by Basic Blue 99 and Basic Red 51, both present in commercial hair dye formulations. Our data show that cells cultured in the 3D model respond differently to those cultured in monolayer. Basic Red 51 dye induces apoptosis an DNA breaks in both models, however, these effects is more pronounced in cells cultured in monolayer. The toxic mode of action of Basic Blue 99 seems to be the induction of cell death, without genotoxic effects, but while the necrotic pathway is observed in HaCaT monolayer cell culture, was apoptosis seen in the Equivalent Human Epidermis (EHE) model. We could also confirm that cells in EHE model, an environment that could better mimic human effects, react differently to chemical stressors than the cells cultivated in 2D., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: There is growing concern regarding problematic smartphone overuse. Practiced mindfulness, the state of being aware of the present moment, may protect against problematic smartphone use by reducing the strength of risk factors., Purpose: We hypothesized that trait mindfulness can reduce the impact of risk factors on a) objective smartphone use and b) subjective problematic smartphone use., Methods: Our sample (n = 135, M age  = 19.15, 68% female) consisted of college students from a large university. Participants completed self-report measures of boredom proneness, impulsivity, technology-related anxiety (nomophobia), trait mindfulness, smartphone use frequency, and problematic use., Results: Higher mindfulness was significantly associated with lower boredom proneness, impulsivity, and problematic use (F = 12.12, p < .01). Hierarchical regression revealed that the positive relationships between nomophobia, and problematic use decreased as mindfulness levels increased. A similar protective effect was observed for boredom proneness, although the effect dissipated as impulsivity rose. A second regression revealed no significant predictors of weekly smartphone use., Conclusions: Effects of nomophobia and boredom proneness on problematic smartphone use diminish with increased mindfulness, but impulsivity may interfere with this. Risk and protective factors for 'addiction' appear unrelated to smartphone use frequency. Future research should examine benefits of mindfulness-based interventions in promoting emotional and cognitive self-regulation, focusing on those who use smartphones in dysfunctional ways., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: National guidelines recommend early palliative care for patients with advanced heart failure, which disproportionately affects rural and minority populations., Objective: To determine the effect of an early palliative care telehealth intervention over 16 weeks on the quality of life, mood, global health, pain, and resource use of patients with advanced heart failure., Design, Setting, and Participants: A single-blind, intervention vs usual care randomized clinical trial was conducted from October 1, 2015, to May 31, 2019, among 415 patients 50 years or older with New York Heart Association class III or IV heart failure or American College of Cardiology stage C or D heart failure at a large Southeastern US academic tertiary medical center and a Veterans Affairs medical center serving high proportions of rural dwellers and African American individuals., Interventions: The ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends Comprehensive Heartcare for Patients and Caregivers) intervention comprises an in-person palliative care consultation and 6 weekly nurse-coach telephonic sessions (20-40 minutes) and monthly follow-up for 48 weeks., Main Outcomes and Measures: Primary outcomes were quality of life (as measured by the Kansas City Cardiomyopathy Questionnaire [KCCQ]: score range, 0-100; higher scores indicate better perceived health status and clinical summary scores ≥50 are considered "fairly good" quality of life; and the Functional Assessment of Chronic Illness Therapy-Palliative-14 [FACIT-Pal-14]: score range, 0-56; higher scores indicate better quality of life) and mood (as measured by the Hospital Anxiety and Depression Scale [HADS]) over 16 weeks. Secondary outcomes were global health (Patient Reported Outcome Measurement System Global Health), pain (Patient Reported Outcome Measurement System Pain Intensity and Interference), and resource use (hospital days and emergency department visits)., Results: Of 415 participants (221 men; baseline mean [SD] age, 63.8 [8.5] years) randomized to ENABLE CHF-PC (n = 208) or usual care (n = 207), 226 (54.5%) were African American, 108 (26.0%) lived in a rural area, and 190 (45.8%) had a high-school education or less, and a mean (SD) baseline KCCQ score of 52.6 (21.0). At week 16, the mean (SE) KCCQ score improved 3.9 (1.3) points in the intervention group vs 2.3 (1.2) in the usual care group (difference, 1.6; SE, 1.7; d = 0.07 [95% CI, -0.09 to 0.24]) and the mean (SE) FACIT-Pal-14 score improved 1.4 (0.6) points in the intervention group vs 0.2 (0.5) points in the usual care group (difference, 1.2; SE, 0.8; d = 0.12 [95% CI, -0.03 to 0.28]). There were no relevant between-group differences in mood (HADS-anxiety, d = -0.02 [95% CI, -0.20 to 0.16]; HADS-depression, d = -0.09 [95% CI, -0.24 to 0.06])., Conclusions and Relevance: This randomized clinical trial with a majority African American sample and baseline good quality of life did not demonstrate improved quality of life or mood with a 16-week early palliative care telehealth intervention. However, pain intensity and interference (secondary outcomes) demonstrated a clinically important improvement., Trial Registration: ClinicalTrials.gov Identifier: NCT02505425.

Importance: Family caregivers of persons with advanced heart failure perform numerous daily tasks to assist their relatives and are at high risk for distress and poor quality of life., Objective: To determine the effect of a nurse-led palliative care telehealth intervention (Educate, Nurture, Advise, Before Life Ends Comprehensive Heart Failure for Patients and Caregivers [ENABLE CHF-PC]) on quality of life and mood of family caregivers of persons with New York Heart Association Class III/IV heart failure over 16 weeks., Design, Setting, and Participants: This single-blind randomized clinical trial enrolled caregivers aged 18 years and older who self-identified as an unpaid close friend or family member who knew the patient well and who was involved with their day-to-day medical care. Participants were recruited from outpatient heart failure clinics at a large academic tertiary care medical center and a Veterans Affairs medical center from August 2016 to October 2018., Intervention: Four weekly psychosocial and problem-solving support telephonic sessions lasting between 20 and 60 minutes facilitated by a trained nurse coach plus monthly follow-up for 48 weeks. The usual care group received no additional intervention., Main Outcomes and Measures: The primary outcomes were quality of life (measured using the Bakas Caregiver Outcomes Scale), mood (anxiety and/or depressive symptoms measured using the Hospital Anxiety and Depression Scale), and burden (measured using the Montgomery-Borgatta Caregiver Burden scales) over 16 weeks. Secondary outcomes were global health (measured using the PROMIS Global Health instrument) and positive aspects of caregiving., Results: A total of 158 family caregivers were randomized, 82 to the intervention and 76 to usual care. The mean (SD) age was 57.9 (11.6) years, 135 (85.4%) were female, 82 (51.9%) were African American, and 103 (65.2%) were the patient's spouse or partner. At week 16, the mean (SE) Bakas Caregiver Outcomes Scale score was 66.9 (2.1) in the intervention group and 63.9 (1.7) in the usual care group; over 16 weeks, the mean (SE) Bakas Caregiver Outcomes Scale score improved 0.7 (1.7) points in the intervention group and 1.1 (1.6) points in the usual care group (difference, -0.4; 95% CI, -5.1 to 4.3; Cohen d = -0.03). At week 16, no relevant between-group differences were observed between the intervention and usual care groups for the Hospital Anxiety and Depression Scale anxiety measure (mean [SE] improvement from baseline, 0.3 [0.3] vs 0.4 [0.3]; difference, -0.1 [0.5]; d = -0.02) or depression measure (mean [SE] improvement from baseline, -0.2 [0.4] vs -0.3 [0.3]; difference, 0.1 [0.5]; d = 0.03). No between-group differences were observed in the Montgomery-Borgatta Caregiver Burden scales (d range, -0.18 to 0.0). Differences in secondary outcomes were also not significant (d range, -0.22 to 0.0)., Conclusions and Relevance: This 2-site randomized clinical trial of a telehealth intervention for family caregivers of patients with advanced heart failure, more than half of whom were African American and most of whom were not distressed at baseline, did not demonstrate clinically better quality of life, mood, or burden compared with usual care over 16 weeks. Future interventions should target distressed caregivers and assess caregiver effects on patient outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT02505425.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Riparian vegetation plays an important role in providing energy to small watercourses and maintaining ecological processes through organic matter input and together with hydrological and geomorphological watercourse characteristics influence on fish assemblages. The goal of this paper was partitioning and quantifying the influence of riparian zone (type of riverbank substrate, bank slope, type of riparian vegetation cover and percentage of riparian vegetation cover on the main channel), physical habitat (stream channel width and depth, type of substrate and aquatic habitat in channel, water velocity and organic matter), water quality (turbidity, temperature, conductivity, pH, dissolved oxygen and chlorophyll concentration) and spatial variables (linear distances between sampled points) on fish assemblages (richness and abundance per species) in headwater streams of the Upper Paraná River basin, Central Brazil. For this purpose, it was performed a variation partitioning analysis between riparian, physical habitat, water and spatial variables sets and a Redundancy Analysis to quantify the influence of variables on the fish assemblages. Only the physical habitat and water quality variables influenced the fish assemblages (richness and abundance per species).

Increased use of drugs is associated with a number of factors including high sensation seeking and sexual minority status (through group-specific minority stress). We sought to examine how personality traits like sensation seeking may influence drug abuse among sexual minority individuals. Participants were 217 emerging adults (Mage = 20.23, SD = 0.85) recruited from Amazon Mechanical Turk (MTurk). Of these participants, 67.7% identified as heterosexual, 9.7% as gay or lesbian, 21.2% as bisexual, and 1.4% indicated other sexual orientations. Sensation seeking and drug abuse were self-reported using the Brief Sensation Seeking Scale and the Drug Abuse Screening Test, respectively. A preliminary multiple analysis of variance indicated no significant mean differences for these variables as a function of sex or sexual orientation. Next, sexual minority status, Brief Sensation Seeking Scale scores, sex and their interactions were entered into a linear regression predicting Drug Abuse Screening Test scores. Results revealed a significant moderation, such that the positive relationship between Brief Sensation Seeking Scale total scores and Drug Abuse Screening Test total scores was stronger for sexual minorities (β = 0.14, P = 0.00) compared to heterosexuals (β = 0.04, P = 0.04), controlling for sex. These results demonstrate, while sensation seeking and sexual minority status may selectively indicate risk for drug use, sexual minorities high in sensation seeking may be at especially high risk for problems related to drug abuse. More research examining the addiction etiology of sexual minority individuals would inform targeted interventions for this population.

The use of functional information in the form of species traits plays an important role in explaining biodiversity patterns and responses to environmental changes. Although relationships between species composition, their traits, and the environment have been extensively studied on a case-by-case basis, results are variable, and it remains unclear how generalizable these relationships are across ecosystems, taxa and spatial scales. To address this gap, we collated 80 datasets from trait-based studies into a global database for metaCommunity Ecology: Species, Traits, Environment and Space; "CESTES". Each dataset includes four matrices: species community abundances or presences/absences across multiple sites, species trait information, environmental variables and spatial coordinates of the sampling sites. The CESTES database is a live database: it will be maintained and expanded in the future as new datasets become available. By its harmonized structure, and the diversity of ecosystem types, taxonomic groups, and spatial scales it covers, the CESTES database provides an important opportunity for synthetic trait-based research in community ecology.

Spontaneous otoacoustic emissions (SOAEs) have been observed in a variety of different vertebrates, including humans and barn owls (Tyto alba). The underlying mechanisms producing the SOAEs and the meaning of their characteristics regarding the frequency selectivity of an individual and species are, however, still under debate. In the present study, we measured SOAE spectra in lightly anesthetized barn owls and suppressed their amplitudes by presenting pure tones at different frequencies and sound levels. Suppression effects were quantified by deriving suppression tuning curves (STCs) with a criterion of 2 dB suppression. SOAEs were found in 100% of ears (n = 14), with an average of 12.7 SOAEs per ear. Across the whole SOAE frequency range of 3.4-10.2 kHz, the distances between neighboring SOAEs were relatively uniform, with a median distance of 430 Hz. The majority (87.6%) of SOAEs were recorded at frequencies that fall within the barn owl's auditory fovea (5-10 kHz). The STCs were V-shaped and sharply tuned, similar to STCs from humans and other species. Between 5 and 10 kHz, the median Q 10dB value of STC was 4.87 and was thus lower than that of owl single-unit neural data. There was no evidence for secondary STC side lobes, as seen in humans. The best thresholds of the STCs varied from 7.0 to 57.5 dB SPL and correlated with SOAE level, such that smaller SOAEs tended to require a higher sound level to be suppressed. While similar, the frequency-threshold curves of auditory-nerve fibers and STCs of SOAEs differ in some respects in their tuning characteristics indicating that SOAE suppression tuning in the barn owl may not directly reflect neural tuning in primary auditory nerve fibers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Objective: Labor market mobility and demographic change contribute to higher numbers of people providing care for their family members from a distance. Concerning the reconciliation of work and care the geographic distance between family members becomes more and more important. For progressive employers, this raises the question to what extent their portfolio is sufficient to support distance caregivers., Methods: Using an interview guideline, 4-6 expert interviews were conducted in 5 partner companies (human resources department, management, executive, works council or employee representative, directors in nursing services; N = 24). The interviews were recorded, transcribed applying standardized procedures, and evaluated using content analysis by means of deductive and inductive categorization., Results: The participating companies had already established numerous reconciliation measures but did not yet focus on distance caregiving. As caregiving issues generally touch on taboo subjects, there is an enhanced need for sensitization and information for all parties involved (management, executives, employees). For distance caregivers, a culture of trust, transparent information and good communication are particularly important., Conclusion: To achieve good reconciliation of work and care, working caregivers and executives need a corporate culture which is sensitive to care issues and able to address previously tabooed aspects. In addition, company portfolios for distance caregiving are needed to provide data-driven, thoughtful and timely support for employees and managers.

Background: Osteoarthritis (OA) is a progressive and multifactorial disease that is associated with aging. A number of changes occur in aged cartilage, such as increased oxidative stress, decreased markers of healthy cartilage, and alterations in the autophagy pathway. Propolis extracts contain a mixture of polyphenols and it has been proved that they have high antioxidant capacity and could regulate the autophagic pathway. Our objective was to evaluate the effect of ethanolic extract of propolis (EEP) on chondrocytes that were stimulated with IL-1β., Methods: Rabbit chondrocytes were isolated and stimulated with IL-1β and treated with EEP. We evaluated cell viability, nitric oxide production, healthy cartilage, and OA markers, and the expression of three proteins associated with the autophagy pathway LC3, ATG5, and AKT1., Results: The EEP treatment reduces the expression of LC3, ATG5, and AKT1, reduces the production of nitric oxide, increases the expression of healthy markers, and reduces OA markers., Conclusions: These results suggest that treatment with EEP in chondrocytes that were stimulated with IL-1β has beneficial effects, such as a decrease in the expression of proteins associated with autophagy, MMP13, and production of nitric oxide, and also increased collagen II.

Recent studies suggest that clear cell renal cell carcinoma (ccRCC) possesses a rare population of cancer stem cells (CSCs) that might contribute to tumor heterogeneity, metastasis and therapeutic resistance. Nevertheless, their relevance for renal cancer is still unclear. In this study, we successfully isolated CSCs from established human ccRCC cell lines. CSCs displayed high expression of the chemokine IL-8 and its receptor CXCR1. While recombinant IL-8 significantly increased CSC number and properties in vitro, CXCR1 inhibition using an anti-CXCR1 antibody or repertaxin significantly reduced these features. After injection into immune-deficient mice, CSCs formed primary tumors that metastasized to the lung and liver. All xenografted tumors in mice expressed high levels of IL-8 and CXCR1. Furthermore, IL-8/CXCR1 expression significantly correlated with decreased overall survival in ccRCC patients. These results suggest that the IL-8/CXCR1 phenotype is associated with CSC-like properties in renal cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland., (© 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β cells. A comprehensive picture of the changes during T1D development is lacking due to limited sample availability, inability to sample longitudinally, and the paucity of technologies enabling comprehensive tissue profiling. Here, we analyzed 1,581 islets from 12 human donors, including eight with T1D, using imaging mass cytometry (IMC). IMC enabled simultaneous measurement of 35 biomarkers with single-cell and spatial resolution. We performed pseudotime analysis of islets through T1D progression from snapshot data to reconstruct the evolution of β cell loss and insulitis. Our analyses revealed that β cell destruction is preceded by a β cell marker loss and by recruitment of cytotoxic and helper T cells. The approaches described herein demonstrate the value of IMC for improving our understanding of T1D pathogenesis, and our data lay the foundation for hypothesis generation and follow-on experiments., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Will I fit into the overcrowded subway? Advanced aging can change our abilities associated with accurately judging the fit between perceived environmental properties and our own actual physical capabilities (affordance judgments). Two experimental studies examined the effects of aging and trainability in affordance judgments. Participants were asked to decide whether their hand fits into a given opening (Aperture Task). We used a detection theory approach to evaluate different judgment characteristics. Study 1 demonstrated that older (N = 39) compared to younger adults (N = 39) produced rather conservative judgments, but did not differ in perceptual sensitivity. Distributions of Hit and False-Alarm rates, as well as risk-perception statements (DOSPERT questionnaire), indicated a heightened concern about potential consequences of misjudgments in older adults. In Study 2, 20 younger and 22 older adults were trained by actually trying to fit their hand into each presented opening. Training included acoustic, haptic and visual feedback. Compared to pre-training, both groups demonstrated significant increases in accuracy when assessed post-training and after a one-week follow-up. While younger adults improved in perceptual sensitivity in post-training as well as in follow-up, the older group adjusted their tendency towards less conservative judgments in both following sessions. Our results are consistent with affordance models that propose a complex and dynamic interplay of different neural processes involved in this skill. Future studies are needed to further elucidate that interplay and the trainability of affordance judgments., Competing Interests: The authors have declared that no competing interests exist.

Background: Palliative care is specialized medical care for people with serious illness that is focused on providing relief from symptoms and stress and improving the quality of life (QOL) for patients and their families. To help the 6.5 million U.S. adults and families affected by heart failure manage the high symptom burden, complex decision-making, and risk of exacerbation and death, the early integration of palliative care is critical and has been recommended by numerous professional organizations. However, few trials have tested early outpatient community-based models of palliative care for patients diagnosed with advanced heart failure and their caregivers. To address this gap, through a series of formative evaluation trials, we translated an oncology early palliative care telehealth intervention for heart failure to create ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends, Comprehensive Heartcare for Patients and Caregivers)., Methods/design: The primary objective of this multisite pragmatic randomized controlled trial is to test the efficacy of ENABLE CHF-PC plus usual heart failure care compared to usual care alone. Community-dwelling persons who are ≥50 years of age with New York Heart Association class III/IV or American Heart Association/American College of Cardiology stage C/D heart failure and their primary caregiver (if present) are being randomized to one of two study arms. The ENABLE CHF-PC intervention group receives usual heart failure care plus an in-person palliative care assessment by a board-certified palliative care provider (caregivers are invited to attend), a series of nurse coach-led, weekly psychoeducational 20 to 60 min phone sessions using a guidebook called Charting Your Course (patients: 6 sessions and caregivers: 4 sessions), and monthly check-in calls. Charting Your Course topical content includes problem-solving, coping, self-care and symptom management, communication, decision-making, advance care planning, and life review (patients only). Primary outcomes include patient QOL and mood (depressive symptoms/anxiety) and caregiver QOL, mood, and burden at 8 and 16 weeks after baseline. Outcomes will be examined using an intention-to-treat approach and mixed effects modeling for repeated measures., Discussion: This trial will determine whether the ENABLE CHF-PC model of concurrent heart failure palliative care is superior to usual heart failure care alone in achieving higher patient and caregiver QOL, improving mood, and lowering burden., Trial Registration: ClinicalTrials.gov, NCT02505425 . Registered on 22 July 2015.

The Mongolian gerbil is a classic animal model for age-related hearing loss. As a prerequisite for studying age-related changes, we characterized cochlear afferent synaptic morphology in young adult gerbils, using immunolabeling and quantitative analysis of confocal microscopic images. Cochlear wholemounts were triple-labeled with a hair-cell marker, a marker of presynaptic ribbons, and a marker of postsynaptic AMPA-type glutamate receptors. Seven cochlear positions covering an equivalent frequency range from 0.5 - 32 kHz were evaluated. The spatial positions of synapses were determined in a coordinate system with reference to their individual inner hair cell. Synapse numbers confirmed previous reports for gerbils (on average, 20-22 afferents per inner hair cell). The volumes of presynaptic ribbons and postsynaptic glutamate receptor patches were positively correlated: larger ribbons associated with larger receptor patches and smaller ribbons with smaller patches. Furthermore, the volumes of both presynaptic ribbons and postsynaptic receptor patches co-varied along the modiolar-pillar and the longitudinal axes of their hair cell. The gradients in ribbon volume are consistent with previous findings in cat, guinea pig, mouse and rat and further support a role in differentiating the physiological properties of type I afferents. However, the positive correlation between the volumes of pre- and postsynaptic elements in the gerbil is different to the opposing gradients found in the mouse, suggesting species-specific differences in the postsynaptic AMPA receptors that are unrelated to the fundamental classes of type I afferents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The advent of mass cytometry increased the number of parameters measured at the single-cell level while decreasing the extent of crosstalk between channels relative to dye-based flow cytometry. Although reduced, spillover still exists in mass cytometry data, and minimizing its effect requires considerable expert knowledge and substantial experimental effort. Here, we describe a novel bead-based compensation workflow and R-based software that estimates and corrects for interference between channels. We performed an in-depth characterization of the spillover properties in mass cytometry, including limitations defined by the linear range of the mass cytometer and the reproducibility of the spillover over time and across machines. We demonstrated the utility of our method in suspension and imaging mass cytometry. To conclude, our approach greatly simplifies the development of new antibody panels, increases flexibility for antibody-metal pairing, opens the way to using less pure isotopes, and improves overall data quality, thereby reducing the risk of reporting cell phenotype artifacts., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)