Online Plain Language Tool and Health Information Quality: A Randomized Clinical Trial.

Importance: Complex and ineffective health communication is a critical source of health inequity and occurs despite repeated policy directives to provide health information that is easy to understand and applies health literacy principles. Objective: To evaluate the effectiveness of the Sydney Health Literacy Lab Health Literacy Editor, an easy-to-use online plain language tool that supports health information providers to apply health literacy guidelines to written health information. Design, Setting, and Participants: This randomized clinical trial, conducted online in Australia from May 2023 to February 2024, included a convenience sample of health information providers with no previous experience using the Health Literacy Editor. Analysts were blinded to study group. Intervention: Participants were randomized 1:1 to the intervention or control group. Participants in the intervention group were provided access to the Health Literacy Editor and a 30-minute online training program prior to editing 3 prespecified health texts. The Health Literacy Editor gives objective, real-time feedback on words and sentences. Control participants revised the texts using their own standard health information development processes. Main Outcomes and Measures: The preregistered primary outcome was the text school grade reading score (using a validated instrument, the Simple Measure of Gobbledygook). Secondary outcomes were text complexity (percentage of text using complex language), use of passive voice (number of instances), and subjective expert ratings (5-point Likert scale corresponding to items on the Patient Education Materials Assessment Tool). Results: A total of 211 participants were randomized, with 105 in the intervention group and 106 in the control group. Of 181 participants in the intention-to-treat analysis (mean [SD] age, 41.0 [11.6] years; 154 women [85.1%]), 86 were in the intervention group and 95 in the control group. Texts revised in the intervention group had significantly improved grade reading scores (mean difference [MD], 2.48 grades; 95% CI, 1.84-3.12 grades; P < .001; Cohen d, 0.99), lower text complexity scores (MD, 6.86; 95% CI, 4.99-8.74; P < .001; Cohen d, 0.95), and less use of passive voice (MD, 0.95 instances; 95% CI, 0.44-1.47 instances; P < .001; Cohen d, 0.53) compared with texts revised in the control group in intention-to-treat analyses. Experts rated texts in the intervention group more favorably for word choice and style than those in the control group (MD, 0.44; 95% CI, 0.25-0.63; P < .001; Cohen d, 0.63), with no loss of meaning or content. Conclusions and Relevance: In this randomized clinical trial, the Health Literacy Editor helped users simplify health information and apply health literacy guidelines to written text. The findings suggest the tool has high potential to improve development of health information for people who have low health literacy. As an online tool, the Health Literacy Editor is also easy to access and implement at scale. Trial Registration: ANZCTR Identifier: ACTRN12623000386639.

Adolescents' perceptions of food outlets in the school neighbourhood and their unhealthy snacking behaviour on the way to and from school.

OBJECTIVE: To understand the relationship between adolescents' unhealthy snacking behaviour during their school journey and their perceived and objective measures of food outlet availability in the school neighbourhood. DESIGN: A cross-sectional survey enquired about socio-demographic information, school transport modes, perceived presence of food outlets in the school neighbourhood and unhealthy food purchase and consumption on the school journey. A geographical information system analysis of the food outlets within 500 m and 1000 m school buffers was undertaken. Data were analysed using generalised linear mixed modelling. SETTING: All twelve secondary schools in Dunedin, Aotearoa New Zealand, March 2020-June 2022. PARTICIPANTS: Adolescents aged 13-18 years (n 725) who reported being familiar with their school neighbourhood. RESULTS: Perceived availability of food outlets in the school neighbourhood was inversely correlated with distance to the closest food outlet from school and positively correlated with food outlet density within 500 m and 1000 m school buffers. Adolescents' purchase and consumption of unhealthy snacks and drinks during the school journey were associated with perceived availability of food outlets and with shorter distance to the closest food outlet from school. Mixed transport users, girls and those living in high-deprivation neighbourhoods had higher odds of purchasing and consuming unhealthy snacks and drinks during the school journey than active transport users, boys and those living in low-deprivation neighbourhoods, respectively. CONCLUSIONS: Adolescents perceptions of the food environment and close access to food outlets in the school neighbourhood may influence adolescents' food purchase and consumption behaviours during the school journey.

Exploring the longitudinal association between stress and unhealthy eating behaviors: The role of physical activity, BMI, and loneliness.

Previous cross-sectional research indicates a link between stress and unhealthy eating, but the longitudinal association remains unknown. This study examined the longitudinal association between perceived stress over a longer time period and unhealthy eating (i.e., sweet and savory snack intake, uncontrolled eating) in a student population. Moreover, we examined whether physical activity buffers such association, and examined whether this buffering effect is stronger for individuals with higher Body Mass Index (BMI) or greater loneliness. Two timepoints of online survey data (Time 1 Oct-Nov 2021, Time 2 May-July 2022) of Dutch university students (n = 1325, 74.7 % female, mean age 22.45 (SD = 2.31)) were used. Results revealed no longitudinal link between stress and snack intake in the total sample, but this association was found in a subgroup of individuals with a higher BMI. Stress at Time 1 was associated with later uncontrolled eating. Physical activity did not moderate the link between stress and unhealthy eating. However, we found a negative longitudinal link between physical activity and uncontrolled eating among individuals with a higher BMI. Our findings suggest that stress does not play an important role in explaining snack intake in university students, but may be associated with uncontrolled eating. Physical activity seems to be linked with a reduction in uncontrolled eating among individuals with a higher BMI specifically. Replication and extension of current findings in a more diverse (e.g., eating disordered) sample would increase insights into the (combined) effects of stress, BMI and physical activity on uncontrolled eating.

Measurement of absolute abundance of crystallins in human and αA N101D transgenic mouse lenses using 15N-labeled crystallin standards.

Stable isotope labeled standards of all major human lens crystallins were created to measure the abundance of lens endogenous crystallins from birth to adulthood. All major human crystallins (αA, αB, ßA2, ßA3/A1, ßA4, ßB1, ßB2, ßB3, γA, γB, γC, γD, γS) were cloned with N-terminal 6 x His tagged SUMO for ease of purification and the ability to generate natural N-termini by SUMO protease cleavage when producing crystallins for structure/function studies. They were then expressed in 15N-enriched media, quantified by mass spectrometry, and mixed in proportions found in young human lens to act as an artificial lens standard. The absolute quantification method was tested using soluble protein from 5-day, 23-day, 18-month, and 18-year-old human lenses spiked with the 15N artificial lens standard. Proteins were trypsinized, relative ratios of light and heavy labeled peptides determined using high-resolution precursor and data independent MS2 scans, and data analysis performed using Skyline software. Crystallin abundances were measured in both human donor lenses and in transgenic mouse αA N101D cataract lenses. Technical replicates of human crystallin abundance measurements were performed with average coefficients of variation of approximately 2% across all 13 crystallins. αA crystallin comprised 27% of the soluble protein of 5-day-old lens and decreased to 16% by 18-years of age. Over this time period αB increased from 6% to 9% and the αA/αB ratio decreased from 4.5/1 to 2/1. γS-crystallin also increased nearly 2-fold from 7% to 12%, becoming the 3rd most abundant protein in adult lens, while ßB1 increased from 14% to 20%, becoming the most abundant crystallin of adult lens. Minor crystallins ßA2, ßB3, and γA comprised only about 1% each of the newborn lens soluble protein, and their abundance dropped precipitously by adulthood. While 9 of the SUMO tagged crystallins were useful for purification of crystallins for structural studies, γA, γB, γC, and γD were resistant to cleavage by SUMO protease. The abundance of WT and N101D human αA in transgenic mouse lenses was approximately 40-fold lower than endogenous mouse αA, but the deamidation mimic human αA N101D was less soluble than human WT αA. The high content of αA and the transient abundance of ßA2, ßB3, and γA in young lens suggest these crystallins play a role in early lens development and growth. ßB1 becoming the most abundant crystallin may result from its role in promoting higher order ß-crystallin oligomerization in mature lens. The full set of human crystallin expression vectors in the Addgene repository should be a useful resource for future crystallin studies. 15N labeling of these crystallins will be useful to accurately quantify crystallins in lens anatomic regions, as well as measure the composition of insoluble light scattering crystallin aggregates. The standards will also be useful to measure the abundance of crystallins expressed in transgenic animal models.

A General and Scalable Method toward Enantioenriched C2-Substituted Azetidines Using Chiral tert-Butanesulfinamides.

Diverse ranges of chiral nitrogen-containing heterocycles serve as a molecular toolbox for modulating a wide array of biological processes, but enantioenriched production of smaller chiral heterocycles is a bottleneck. There is a lack of general approaches for the stereoselective preparation of chiral 4-membered monocyclic C2-substituted azetidines, where many routes to different substitution types are possible, but no simple and common approach exists. To bridge this gap, inexpensive and widely available chiral tert-butanesulfinamides are harnessed for chiral induction with 1,3-bis-electrophilic 3-chloropropanal, providing a three-step approach to C2-substituted azetidines with aryl, vinyl, allyl, branched alkyl, and linear alkyl substituents. Eleven azetidine products are produced, and the approach is shown to be effective on a gram-scale with a single purification of the protected azetidine product in 44% yield over three steps in an 85:15 diastereomeric ratio. In most cases, the diastereomers are separable using normal phase chromatography, often resulting in previously elusive enantiopure azetidine products. Protected azetidines were shown to undergo rapid and efficient sulfinamide cleavage, producing an azetidine hydrochloride salt that was subjected to derivatization reactions, highlighting the method's applicability to medicinal chemistry approaches.

Two-month ketogenic diet alters systemic and brain metabolism in middle-aged female mice.

The ketogenic diet (KD) is a very low-carbohydrate, high-fat diet that reduces glucose catabolism and enhances ß-oxidation and ketogenesis. While research in female rodents is limited, research in male rodents suggests that ketogenic interventions initiated at midlife may slow age-related cognitive decline, as well as preserve muscle mass and physical function later in life. This study aimed to investigate the effects of a KD on global metabolic changes in middle-aged females to inform potential mechanisms behind the anti-aging effects of this diet in an understudied sex. Targeted 1H-NMR metabolomics was conducted on serum, the liver, the kidney, and the gastrocnemius muscle, as well as the cortex and the hippocampal brain regions in 16-month-old female mice after a 2-month KD. Analysis of the serum and liver metabolome revealed that the 2-month KD resulted in increased concentrations of fatty acid catabolism metabolites, as well as system-wide elevations in ketones, consistent with the ketogenic phenotype. Metabolites involved in the glucose-alanine cycle were altered in the gastrocnemius muscle, serum and the liver. Other tissue-specific alterations were detected, including distinct effects on hepatic and renal one-carbon metabolism, as well as region specific differences in metabolism across hippocampal and cortical parts of the brain. Alterations to hippocampal metabolites involved in myelinogenesis could relate to the potential beneficial effects of a KD on memory.

Effects of the maternal social environment on the mating signals and mate preferences of adult offspring in Enchenopa treehoppers.

Much is known about how the maternal environment can shape offspring traits via intergenerational effects. It is less clear, however, whether such effects may reach adult offspring sexual traits, with potential consequences for sexual selection and speciation. Here, we report effects of adult female aggregation density on the mating signals and mate preferences of their offspring in an insect that communicates via plant-borne vibrational signals. We experimentally manipulated the density of aggregations experienced by egg-laying mothers, reared the offspring in standard densities, and tested for corresponding differences in their signals and preferences. We detected a strong effect in male signals, with sons of mothers that experienced low aggregation density signalling more. We also detected a weak effect on female mate preferences, with daughters of mothers that experienced low aggregation density being less selective. These adjustments may help males and females find mates and secure matings in low densities, if the conditions they encounter correspond to those their mothers experienced. Our results thus extend theory regarding adjustments to the social environment to the scale of intergenerational effects, with maternal social environments influencing the expression of the sexual traits of adult offspring.

Effect of a peer-led emergency department behavioral intervention on non-fatal opioid overdose: 18-month outcome in the Navigator randomized controlled trial.

BACKGROUND AND AIMS: Emergency departments (EDs) provide an opportunity to identify people at risk of overdose and reduce the risk. We evaluated the effect of an ED behavioral intervention delivered by peer recovery support specialists (PRSSs) on non-fatal opioid overdose. DESIGN: Two-arm, randomized trial. SETTING: Two EDs in Rhode Island, USA. PARTICIPANTS: ED patients presenting with an opioid overdose, complications of opioid use disorder or a recent history of opioid overdose (November 2018-May 2021). Among 648 participants, the mean age was 36.9 years, 68.2% were male and 68.5% were White. INTERVENTION AND COMPARATOR: Participants were randomized to receive a behavioral intervention from a PRSS (n = 323) or a licensed clinical social worker (LICSW) (n = 325). PRSS and LICSW used evidence-based interviewing and intervention techniques, informed by their lived experience (PRSS) or clinical theory and practice (LICSW). MEASUREMENTS: We identified non-fatal opioid overdoses in the 18 months following the ED visit through linkage to statewide emergency medical services data using a validated case definition. The primary outcome was any non-fatal opioid overdose during the 18-month follow-up period. FINDINGS: Among 323 participants randomized to the PRSS arm, 81 (25.1%) had a non-fatal opioid overdose during follow-up, compared with 95 (29.2%) of 325 participants randomized to the LICSW arm (P = 0.24). There was no statistically significant difference in the effectiveness of randomization to the PRSS arm versus the LICSW arm on the risk of non-fatal opioid overdose, adjusting for the history of previous overdose (relative risk = 0.86, 95% confidence interval = 0.67-1.11). CONCLUSIONS: In Rhode Island, USA, over one-in-four emergency department patients at high risk of overdose experience a non-fatal opioid overdose in the 18 months post-discharge. We found no evidence that the risk of non-fatal opioid overdose differs for emergency department patients receiving a behavioral intervention from a peer recovery support specialist versus a licensed clinical social worker.

Clinical outcomes of nurse-coordinated interventions for frail older adults discharged from hospital: A systematic review and meta-analysis.

AIM: To determine the effects of nurse-coordinated interventions in improving readmissions, cumulative hospital stay, mortality, functional ability and quality of life for frail older adults discharged from hospital. DESIGN: Systematic review with meta-analysis. METHODS: A systematic search using key search terms of 'frailty', 'geriatric', 'hospital' and 'nurse'. Covidence was used to screen individual studies. Studies were included that addressed frail older adults, incorporated a significant nursing role in the intervention and were implemented during hospital admission with a focus on transition from hospital to home. DATA SOURCES: This review searched MEDLINE (Ovid), CINAHL (EBSCO), PubMed (EBSCO), Scopus, Embase (Ovid) and Cochrane library for studies published between 2000 and September 2023. RESULTS: Of 7945 abstracts screened, a total 16 randomised controlled trials were identified. The 16 randomised controlled trials had a total of 8795 participants, included in analysis. Due to the heterogeneity of the outcome measures used meta-analysis could only be completed on readmission (n = 13) and mortality (n = 9). All other remaining outcome measures were reported through narrative synthesis. A total of 59 different outcome measure assessments and tools were used between studies. Meta-analysis found statistically significant intervention effect at 1-month readmission only. No other statistically significant effects were found on any other time point or outcome. CONCLUSION: Nurse-coordinated interventions have a significant effect on 1-month readmissions for frail older adults discharged from hospital. The positive effect of interventions on other health outcomes within studies were mixed and indistinct, this is attributed to the large heterogeneity between studies and outcome measures. RELEVANCE TO CLINICAL PRACTICE: This review should inform policy around transitional care recommendations at local, national and international levels. Nurses, who constitute half of the global health workforce, are ideally situated to provide transitional care interventions. Nurse-coordinated models of care, which identify patient needs and facilitate the continuation of care into the community improve patient outcomes. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Review findings will be useful for key stakeholders, clinicians and researchers to learn more about the essential elements of nurse-coordinated transitional care interventions that are best targeted to meet the needs of frail older adults. IMPACT: When frail older adults experience transitions in care, for example discharging from hospital to home, there is an increased risk of adverse events, such as institutionalisation, hospitalisation, disability and death. Nurse-coordinated transitional care models have shown to be a potential solution to support adults with specific chronic diseases, but there is more to be known about the effectiveness of interventions in frail older adults. This review demonstrated the positive impact of nurse-coordinated interventions in improving readmissions for up to 1 month post-discharge, helping to inform future transitional care interventions to better support the needs of frail older adults. REPORTING METHOD: This systematic review was reported in accordance with the Referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Characterization of different-sized human αA-crystallin homomers and implications to Asp151 isomerization.

Site-specific modifications of aspartate residues spontaneously occur in crystallin, the major protein in the lens. One of the primary modification sites is Asp151 in αA-crystallin. Isomerization and racemization alter the crystallin backbone structure, reducing its stability by inducing abnormal crystallin-crystallin interactions and ultimately leading to the insolubilization of crystallin complexes. These changes are considered significant factors in the formation of senile cataracts. However, the mechanisms driving spontaneous isomerization and racemization have not been experimentally demonstrated. In this study, we generated αA-crystallins with different homo-oligomeric sizes and/or containing an asparagine residue at position 151, which is more prone to isomerization and racemization. We characterized their structure, hydrophobicity, chaperone-like function, and heat stability, and examined their propensity for isomerization and racemization. The results show that the two differently sized αA-crystallin variants possessed similar secondary structures but exhibited different chaperone-like functions depending on their oligomeric sizes. The rate of isomerization and racemization of Asp151, as assessed by the deamidation of Asn151, was also found to depend on the oligomeric sizes of αA-crystallin. The predominant isomerization product via deamidation of Asn151 in the different-sized αA-crystallin variants was L-ß-Asp in vitro, while various modifications occurred around Asp151 in vivo. The disparity between the findings of this in vitro study and in vivo studies suggests that the isomerization of Asp151 in vivo may be more complex than what occurs in vitro.

Consumption of alcohol-free and alcoholic beverages among Dutch university students: Substitution or addition?

INTRODUCTION: Alcohol-free drinks are suggested as healthy alternatives for alcohol consumption. To achieve benefits, alcohol-free beverages must be consumed as a substitute for alcoholic beverages, not in addition. This study examined in a student sample (i) the frequency/quantity of alcohol(-free) consumption; (ii) the relationship between alcohol-free and alcohol consumption; (iii) alcohol-free drinks as substitution or in addition to alcoholic drinks; and (iv) possible gender differences. METHODS: Survey data regarding alcohol(-free) consumption (May-June 2022) of Dutch university students (N = 4.318, females 70.2%; males 28.5%, average age 22.6 years [SD = 2.4]). RESULTS: (i) A total of 42.8% of the students indicated they had never consumed alcohol-free versus 10.1% who never consumed alcoholic beverages; (ii) the group who recently consumed alcohol-free also most often recently consumed alcoholic beverages (42.7%). The group that had never consumed alcohol-free drank on average more alcoholic beverages (M = 3.98 on a drinking day) compared to past and recent alcohol-free drinkers (respectively, M = 3.44 and M = 3.59). (iii) Most students (54.9%) reported drinking alcohol-free beverages in addition to alcohol, 17.4% indicated using it as a substitution. Students who consumed alcohol-free as 'substitution' were older, more often living alone or with a partner, less often living with parents and more often involved in a steady relationship compared to students who consumed in 'addition'. (iv) No prominent gender differences were found. DISCUSSION AND CONCLUSIONS: The majority of students remained consuming the same number of alcoholic beverages since they started consuming alcohol-free beverages, pointing to an addition effect. A small group did use alcohol-free beverages as a substitute for their alcohol consumption.

A Decision Aid for Patients Considering Surgery for Sciatica: Codesign and User-Testing With Patients and Clinicians.

BACKGROUND: Surgery can help patients with leg pain caused by sciatica recover faster, but by 12 months outcomes are similar to nonsurgical management. For many the decision to have surgery may require reflection, and patient decision aids are an evidence-based clinical tool that can help guide patients through this decision. OBJECTIVE: The aim of this study was to develop and refine a decision aid for patients with sciatica who are deciding whether to have surgery or 'wait and see' (i.e., try nonsurgical management first). DESIGN: Semistructured interviews with think-aloud user-testing protocol. PARTICIPANTS: Twenty clinicians and 20 patients with lived experience of low back pain or sciatica. OUTCOME MEASURES: Items from Technology Acceptance Model, Preparation for Decision Making Scale and Decision Quality Instrument for Herniated Disc 2.0 (knowledge instrument). METHODS: The prototype integrated relevant research with working group perspectives, decision aid standards and health literacy guidelines. The research team refined the prototype through seven rounds of user-testing, which involved discussing user-testing feedback and implementing changes before progressing to the next round. RESULTS: As a result of working group feedback, the decision aid was divided into sections: before, during and after a visit to the surgeon. Across all rounds of user-testing, clinicians rated the resource 5.9/7 (SD = 1.0) for perceived usefulness, and 6.0/7 for perceived ease of use (SD = 0.8). Patients reported the decision aid was easy to understand, on average correctly answering 3.4/5 knowledge questions (SD = 1.2) about surgery for sciatica. The grade reading score for the website was 9.0. Patients scored highly on preparation for decision-making (4.4/5, SD = 0.7), suggesting strong potential to empower patients. Interview feedback showed that patients and clinicians felt the decision aid would encourage question-asking and help patients reflect on personal values. CONCLUSIONS: Clinicians found the decision aid acceptable, patients found it was easy to understand and both groups felt it would empower patients to actively engage in their care and come to an informed decision that aligned with personal values. Input from the working group and user-testing was crucial for ensuring that the decision aid met patient and clinician needs. PATIENT OR PUBLIC CONTRIBUTION: Patients and clinicians contributed to prototype development via the working group.

GATA2 heterozygosity causes an epigenetic feedback mechanism resulting in myeloid and erythroid dysplasia.

The transcription factor GATA2 has a pivotal role in haematopoiesis. Heterozygous germline GATA2 mutations result in a syndrome characterized by immunodeficiency, bone marrow failure and predispositions to myelodysplastic syndrome (MDS) and acute myeloid leukaemia. Clinical symptoms in these patients are diverse and mechanisms driving GATA2-related phenotypes are largely unknown. To explore the impact of GATA2 haploinsufficiency on haematopoiesis, we generated a zebrafish model carrying a heterozygous mutation of gata2b (gata2b+/-), an orthologue of GATA2. Morphological analysis revealed myeloid and erythroid dysplasia in gata2b+/- kidney marrow. Because Gata2b could affect both transcription and chromatin accessibility during lineage differentiation, this was assessed by single-cell (sc) RNA-seq and single-nucleus (sn) ATAC-seq. Sn-ATAC-seq showed that the co-accessibility between the transcription start site (TSS) and a -3.5-4.1 kb putative enhancer was more robust in gata2b+/- zebrafish HSPCs compared to wild type, increasing gata2b expression and resulting in higher genome-wide Gata2b motif use in HSPCs. As a result of increased accessibility of the gata2b locus, gata2b+/- chromatin was also more accessible during lineage differentiation. scRNA-seq data revealed myeloid differentiation defects, that is, impaired cell cycle progression, reduced expression of cebpa and cebpb and increased signatures of ribosome biogenesis. These data also revealed a differentiation delay in erythroid progenitors, aberrant proliferative signatures and down-regulation of Gata1a, a master regulator of erythropoiesis, which worsened with age. These findings suggest that cell-intrinsic compensatory mechanisms, needed to obtain normal levels of Gata2b in heterozygous HSPCs to maintain their integrity, result in aberrant lineage differentiation, thereby representing a critical step in the predisposition to MDS.

The prototype of a frailty learning health system: The HARMONY Model.

Introduction: Rapid translation of research findings into clinical practice through innovation is critical to improve health systems and patient outcomes. Access to efficient systems of learning underpinned with real-time data are the future of healthcare. This type of health system will decrease unwarranted clinical variation, accelerate rapid evidence translation, and improve overall healthcare quality. Methods: This paper aims to describe The HARMONY model (acHieving dAta-dRiven quality iMprovement to enhance frailty Outcomes using a learNing health sYstem), a new frailty learning health system model of implementation science and practice improvement. The HARMONY model provides a prototype for clinical quality registry infrastructure and partnership within health care. Results: The HARMONY model was applied to the Western Sydney Clinical Frailty Registry as the prototype exemplar. The model networks longitudinal frailty data into an accessible and useable format for learning. Creating local capability that networks current data infrastructures to translate and improve quality of care in real-time. Conclusion: This prototype provides a model of registry data feedback and quality improvement processes in an inpatient aged care and rehabilitation hospital setting to help reduce clinical variation, enhance research translation capacity, and improve care quality.

A palliative care goals model for people with dementia and their family: Consensus achieved in an international Delphi study.

BACKGROUND: Advance care planning in dementia includes supporting the person and their family to consider important goals of care. International research reports the importance of psycho-social-spiritual aspects towards end of life. AIM: To develop a multidimensional international palliative care goals model in dementia for use in practice. DESIGN: International Delphi study integrating consensus and evidence from a meta-qualitative study. The Delphi panel rated statements about the model on a 5-point agreement scale. The criteria for consensus were pre-specified. SETTING/PARTICIPANTS: Seventeen researchers from eight countries developed an initial model, and 169 candidate panellists were invited to the international online Delphi study. RESULTS: Panellists (107; response 63.3%) resided in 33 countries. The model comprised four main care goals: (1) Comfort ensured; (2) Control over function maintained; (3) Identity protected and personhood respected and (4) Coping with grief and loss-person and caregiver supported. The model reflects how needs and care goals change over time with the progression of dementia, concluding with bereavement support. The first version of the model achieved a consensus after which it was slightly refined based on feedback. We did not achieve a consensus on adding a goal of life prolongation, and on use of the model by people with dementia and family themselves. CONCLUSION: A new palliative care goals model for people with dementia and their families includes relationship aspects for use by professionals and achieved a consensus among a panel with diverse cultural background. The position of life prolongation in relation to palliative care goals needs further research.

Is the Association Between Alcohol Consumption and Mental Well-Being in University Students Linear, Curvilinear or Absent?

Background: Both alcohol consumption and mental well-being problems have been found to be prevalent in higher educated students and often have severe consequences. However, previous findings of the association between these constructs are mixed, possibly because often linear models are fitted, while some theories suggest a curvilinear association between the two concepts. Objectives: To clarify previously mixed findings, the current study compared curvilinear and linear models for the relationship between alcohol consumption and mental well-being in university students. Because of potential gender differences in this relationship, these models were explored for females and males separately. Data from the first cross-sectional online survey wave of the Healthy Student Life project including 2,631 female and 998 male students was used. The Alcohol Use Disorders Identification Test-consumption was used to measure alcohol consumption. Mental well-being was assessed by six sub-concepts (i.e., depressive symptoms, anxiety, stress, life satisfaction, happiness, and self-rated mental health). Results: For females both linear (for anxiety, life satisfaction, and self-rated mental health) and curvilinear (for depression, stress, and happiness) associations were found, while for males no support for either curvilinear or linear models was found. Conclusions: Results should be interpreted with caution due to the small effect sizes in the relationships for females but may suggest that testing the curvilinear association between alcohol consumption and mental well-being is an important future endeavor.

A Large Postmortem Database of COVID-19 Patients Can Inform Disease Research and Public Policy Decision Making.

CONTEXT.­: Autopsies performed on COVID-19 patients have provided critical information about SARS-CoV-2's tropism, mechanisms of tissue injury, and the spectrum of disease. OBJECTIVE.­: To provide an updated database of postmortem disease in COVID-19 patients, assess relationships among clinical and pathologic variables, evaluate the accuracy of death certification, and correlate disease variables to causes of death. DESIGN.­: The 272 postmortem examinations reported in this paper were submitted by 14 pathologists from 9 medical or forensic institutions across the United States. The study spans the eras of the 3 principal COVID-19 strains and incorporates surveyed demographic, clinical, and postmortem data from decedents infected with SARS-CoV-2, including primary and contributing causes of death. It is the largest database of its kind to date. RESULTS.­: Demographics of the decedents reported here correspond well to national statistics. Primary causes of death as determined by autopsy and official death certificates were significantly correlated. When specifically cited disease conditions found at autopsy were correlated with COVID-19 versus non-COVID-19 death, only lung findings characteristic of SARS-CoV-2 infection or the absence of lung findings were significantly associated. CONCLUSIONS.­: Changes in hospitalization and disease likely stem from longer lifespans after COVID-19 diagnosis and alteration in treatment approaches. Although Omicron variants preferentially replicate in the upper airways, autopsied patients who died of COVID-19 in that time period showed the same lung damage as earlier decedents. Most importantly, findings suggest that there are still unelucidated risk factors for death from COVID-19 including possibly genetic susceptibility.

Complications after CyPass® Micro-Stent explantation: a case series.

PURPOSE: To describe the in toto explantation of the CyPass® Micro-Stent and its conceivable complications. METHODS: This is a case series of eighteen eyes from fourteen patients who underwent CyPass® Micro-Stent implantation due to mild to moderate glaucoma and who subsequently suffered from loss of endothelial cell density. Consequently, the CyPass® Micro-Stent was in toto explanted. The surgical procedure and its complications are described and compared with trimming of the CyPass® Micro-Stent. RESULTS: A postoperative hyphema was developed in 8 of the 18 eyes. In four of them the hyphema was self-limiting, while in two patients an anterior chamber irrigation was necessary. One patient suffered from a severe intracameral bleeding and iridodialysis during explantation, so that the base of the iris had to be scleral fixated. The remaining explantations were without complications. CONCLUSION: Dealing with implanted CyPass® Micro-Stents poses a challenge for ophthalmic surgeons. An in toto removal can be traumatic, since the CyPass stent often is fibrotic encapsulated and fused with the surrounding tissue. Alternatively, trimming of the CyPass is also a viable option to avoid further endothelial damage. Reported complications of CyPass trimming are consistent with those that can occur after explantation. Further data on the development of the endothelial cells after trimming or explantation are not yet available. Therefore, it remains open whether trimming of the CyPass, in contrast to complete removal, carries the risk of further endothelial cell loss.

The α-crystallin Chaperones Undergo a Quasi-ordered Co-aggregation Process in Response to Saturating Client Interaction.

Small heat shock proteins (sHSPs) are ATP-independent chaperones vital to cellular proteostasis, preventing protein aggregation events linked to various human diseases including cataract. The α-crystallins, αA-crystallin (αAc) and αB-crystallin (αBc), represent archetypal sHSPs that exhibit complex polydispersed oligomeric assemblies and rapid subunit exchange dynamics. Yet, our understanding of how this plasticity contributes to chaperone function remains poorly understood. Using biochemical and biophysical analyses combined with single-particle electron microscopy (EM), we examined structural changes in αAc, αBc and native heteromeric lens α-crystallins (αLc) in their apo-states and at varying degree of chaperone saturation leading to co-aggregation, using lysozyme and insulin as model clients. Quantitative single-particle analysis unveiled a continuous spectrum of oligomeric states formed during the co-aggregation process, marked by significant client-triggered expansion and quasi-ordered elongation of the sHSP oligomeric scaffold, whereby the native cage-like sHSP assembly displays a directional growth to accommodate saturating conditions of client sequestration. These structural modifications culminated in an apparent amorphous collapse of chaperone-client complexes, resulting in the creation of co-aggregates capable of scattering visible light. Intriguingly, these co-aggregates maintain internal morphological features of highly elongated sHSP oligomers with striking resemblance to polymeric α-crystallin species isolated from aged lens tissue. This mechanism appears consistent across αAc, αBc and αLc, albeit with varying degrees of susceptibility to client-induced co-aggregation. Importantly, our findings suggest that client-induced co-aggregation follows a distinctive mechanistic and quasi-ordered trajectory, distinct from a purely amorphous process. These insights reshape our understanding of the physiological and pathophysiological co-aggregation processes of α-crystallins, carrying potential implications for a pathway toward cataract formation.