Novel functional insights into the microbiome inhabiting marine plastic debris: critical considerations to counteract the challenges of thin biofilms using multi-omics and comparative metaproteomics.

BACKGROUND: Microbial functioning on marine plastic surfaces has been poorly documented, especially within cold climates where temperature likely impacts microbial activity and the presence of hydrocarbonoclastic microorganisms. To date, only two studies have used metaproteomics to unravel microbial genotype-phenotype linkages in the marine 'plastisphere', and these have revealed the dominance of photosynthetic microorganisms within warm climates. Advancing the functional representation of the marine plastisphere is vital for the development of specific databases cataloging the functional diversity of the associated microorganisms and their peptide and protein sequences, to fuel biotechnological discoveries. Here, we provide a comprehensive assessment for plastisphere metaproteomics, using multi-omics and data mining on thin plastic biofilms to provide unique insights into plastisphere metabolism. Our robust experimental design assessed DNA/protein co-extraction and cell lysis strategies, proteomics workflows, and diverse protein search databases, to resolve the active plastisphere taxa and their expressed functions from an understudied cold environment. RESULTS: For the first time, we demonstrate the predominance and activity of hydrocarbonoclastic genera (Psychrobacter, Flavobacterium, Pseudomonas) within a primarily heterotrophic plastisphere. Correspondingly, oxidative phosphorylation, the citrate cycle, and carbohydrate metabolism were the dominant pathways expressed. Quorum sensing and toxin-associated proteins of Streptomyces were indicative of inter-community interactions. Stress response proteins expressed by Psychrobacter, Planococcus, and Pseudoalteromonas and proteins mediating xenobiotics degradation in Psychrobacter and Pseudoalteromonas suggested phenotypic adaptations to the toxic chemical microenvironment of the plastisphere. Interestingly, a targeted search strategy identified plastic biodegradation enzymes, including polyamidase, hydrolase, and depolymerase, expressed by rare taxa. The expression of virulence factors and mechanisms of antimicrobial resistance suggested pathogenic genera were active, despite representing a minor component of the plastisphere community. CONCLUSION: Our study addresses a critical gap in understanding the functioning of the marine plastisphere, contributing new insights into the function and ecology of an emerging and important microbial niche. Our comprehensive multi-omics and comparative metaproteomics experimental design enhances biological interpretations to provide new perspectives on microorganisms of potential biotechnological significance beyond biodegradation and to improve the assessment of the risks associated with microorganisms colonizing marine plastic pollution. Video Abstract.

Individual differences and the transposed letter effect during reading.

When a preview contains substituted letters (SL; markey) word identification is more disrupted for a target word (monkey), compared to when the preview contains transposed letters (TL; mnokey). The transposed letter effect demonstrates that letter positions are encoded more flexibly than letter identities, and is a robust finding in adults. However, letter position encoding has been shown to gradually become more flexible as reading skills develop. It is unclear whether letter position encoding flexibility reaches maturation in skilled adult readers, or whether some differences in the magnitude of the TL effect remain in relation to individual differences in cognitive skills. We examined 100 skilled adult readers who read sentences containing a correct, TL or SL preview. Previews were replaced by the correct target word when the reader's gaze triggered an invisible boundary. Cognitive skills were assessed and grouped based on overlapping variance via Principal Components Analysis (PCA) and subsequently used to predict eye movement measures for each condition. Consistent with previous literature, adult readers were found to generally encode letter position more flexibly than letter identity. Very few differences were found in the magnitude of TL effects between adults based on individual differences in cognitive skills. The flexibility of letter position encoding appears to reach maturation (or near maturation) in skilled adult readers.

A Behaviorally Informed Mobile App to Improve the Nutritional Quality of Grocery Shopping (SwapSHOP): Feasibility Randomized Controlled Trial.

BACKGROUND: Interventions targeting the nutritional quality of grocery shopping have the potential to help improve diet and health outcomes. OBJECTIVE: This study aims to assess the feasibility and acceptability of receiving advice on healthier food purchases through SwapSHOP, a behaviorally informed smartphone app that allows users to scan barcodes of grocery products from the United Kingdom, providing nutritional information and personalized swap suggestions to encourage healthier purchases. METHODS: We randomized adult volunteers in a 6-arm parallel-group controlled feasibility trial. Participants used the SwapSHOP app to record their grocery shopping during a 2-week run-in period and were individually randomized in a 3:1 ratio to either intervention or control arms within 3 strata related to a nutrient of concern of their choice: saturated fat (SFA), sugar, or salt. Participants randomized to the intervention received the SwapSHOP app with a healthier swap function, goal setting, and personalized feedback. Participants in the control group were instructed to use a simpler version of the app to log all their food purchases without receiving any guidance or advice. The primary outcome was the feasibility of progression to a full trial, including app use and follow-up rates at 6 weeks. The secondary outcomes included other feasibility outcomes, process and qualitative measures, and exploratory effectiveness outcomes to assess changes in the nutrient content of the purchased foods. RESULTS: A total of 112 participants were randomized into 3 groups: SFA (n=38 intervention and n=13 control), sugar (n=40 intervention and n=15 control), and salt (n=5 intervention and n=1 control, not analyzed). The 2 progression criteria were met for SFA and sugar: 81% (30/37) and 87% (34/39) of intervention participants in the SFA and sugar groups, respectively, used the app to obtain healthier swaps, and 89% (68/76) of intervention participants and 96% (23/24) of control participants completed follow-up by scanning all purchases over the follow-up period. The process and qualitative outcomes suggested that the intervention was acceptable and has the potential to influence shopping behaviors. There were reductions of -0.56 g per 100 g (95% CI -1.02 to -0.19) in SFA and -1 g per 100 g (95% CI -1.97 to -0.03) in total sugars across all food purchases in the intervention groups. CONCLUSIONS: People were willing to use the SwapSHOP app to help reduce sugar and SFA (but not salt) in their grocery shopping. Adherence and follow-up rates suggest that a full trial is feasible. Given the suggestive evidence indicating that the intervention resulted in reductions in sugars and SFA, a definitive trial is necessary to target improvements in health outcomes. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN13022312; https://doi.org/10.1186/ISRCTN13022312.

Clinical trials of pharmacological interventions for SARS-CoV-2 published in leading medical journals report adherence but not how it was assessed.

AIMS: Adherence to pharmacological interventions in clinical trials is crucial for accurate identification of beneficial and adverse outcomes. The ways in which adherence to interventions should be reported in trial publications are described in the Template for Intervention Description and Replication (TIDieR), a 12-item extension of the Consolidated Standards of Reporting Trials reporting guidelines. The objective of this study was to assess compliance with TIDieR Items 11 and 12 of randomized controlled trials (RCTs) of interventions in SARS-CoV-2 infection published in 5 selected journals during 2021. METHODS: We assessed pharmacological interventions for SARS-CoV-2 infection reported in RCTs published in 2021 in the Annals of Internal Medicine, The BMJ, JAMA, The Lancet and The New England Journal for Medicine for compliance with TIDieR items addressing intervention adherence (Items 11 and 12). We calculated proportional adherence for pharmacological and comparator interventions where available. RESULTS: We found 75 eligible RCTs. Twenty-eight (37%) reported results of SARS-CoV-2 vaccinations. Compliance with Items 11 and 12 could be assessed in 71 of these 75. Of the 71 RCTs, 37 (52%) reported how adherence was assessed (Item 11), and 70 reported adherence rates (Item 12). Only 1 of the 71 RCTs (1.4%, 0-7.6%) fully complied with TIDieR Items 11 and 12. CONCLUSION: Half of RCTs of SARS-CoV-2 pharmacological interventions published in leading medical journals in 2021 complied with reporting of how adherence assessments were made and almost none complied with both TIDieR Items 11 and 12. The implications for interpretation, application and replication of findings based on these publications warrant consideration.

Anticipatory prescribing in community end-of-life care.

OBJECTIVES: Our work aims to critically review the use of anticipatory medicines in our inner-city hospice community population and whether our current practices are fit for purpose. METHODS: Retrospective audit of community palliative care patients at the end-of-life prescribed anticipatory medicines within a 3-month period. Anticipatory charts and case notes reviewed. Intervention included updating local guidelines, local teaching for medical and non-medical prescribers and sharing results nationally. Eighteen months later, reaudit was performed assessing impact. RESULTS: In total, 76 patients included. 75/76 (99%) were prescribed an analgesic, antiemetic, antisecretory and anxiolytic. 49/76 (64%) were administered 'as required' medications at home. Haloperidol was the favoured antiemetic (88%), costing our hospice ~£2000/month. Case note review highlighted prescribing and administration issues. Reaudit showed a reduction in prescriptions of antisecretory (by 57%) and antiemetic (by 50%), with a wider range of antiemetics (levomepromazine 47%, haloperidol 35%, cyclizine 14%, metoclopramide 3%) indicating individualised prescribing. Those without an antiemetic prescribed did not later require one dispensing. CONCLUSION: Our work challenges the orthodoxy that an analgesic, antiemetic, antisecretory and anxiolytic medication must always be included for effective anticipatory prescribing. Antiemetics may not be universally required and individualised prescribing was cost-effective and safe at a local level. Further work evaluating the impacts of altered practice on patients, caregivers, professionals and in other community settings is required.

Endogenous renal adiponectin drives gluconeogenesis through enhancing pyruvate and fatty acid utilization.

Adiponectin is a secretory protein, primarily produced in adipocytes. However, low but detectable expression of adiponectin can be observed in cell types beyond adipocytes, particularly in kidney tubular cells, but its local renal role is unknown. We assessed the impact of renal adiponectin by utilizing male inducible kidney tubular cell-specific adiponectin overexpression or knockout mice. Kidney-specific adiponectin overexpression induces a doubling of phosphoenolpyruvate carboxylase expression and enhanced pyruvate-mediated glucose production, tricarboxylic acid cycle intermediates and an upregulation of fatty acid oxidation (FAO). Inhibition of FAO reduces the adiponectin-induced enhancement of glucose production, highlighting the role of FAO in the induction of renal gluconeogenesis. In contrast, mice lacking adiponectin in the kidney exhibit enhanced glucose tolerance, lower utilization and greater accumulation of lipid species. Hence, renal adiponectin is an inducer of gluconeogenesis by driving enhanced local FAO and further underlines the important systemic contribution of renal gluconeogenesis.

Protective roles of adiponectin and molecular signatures of HNF4α and PPARα as downstream targets of adiponectin in pancreatic ß cells.

The disease progression of the metabolic syndrome is associated with prolonged hyperlipidemia and insulin resistance, eventually giving rise to impaired insulin secretion, often concomitant with hypoadiponectinemia. As an adipose tissue derived hormone, adiponectin is beneficial for insulin secretion and ß cell health and differentiation. However, the down-stream pathway of adiponectin in the pancreatic islets has not been studied extensively. Here, along with the overall reduction of endocrine pancreatic function in islets from adiponectin KO mice, we examine PPARα and HNF4α as additional down-regulated transcription factors during a prolonged metabolic challenge. To elucidate the function of ß cell-specific PPARα and HNF4α expression, we developed doxycycline inducible pancreatic ß cell-specific PPARα (ß-PPARα) and HNF4α (ß-HNF4α) overexpression mice. ß-PPARα mice exhibited improved protection from lipotoxicity, but elevated ß-oxidative damage in the islets, and also displayed lowered phospholipid levels and impaired glucose-stimulated insulin secretion. ß-HNF4α mice showed a more severe phenotype when compared to ß-PPARα mice, characterized by lower body weight, small islet mass and impaired insulin secretion. RNA-sequencing of the islets of these models highlights overlapping yet unique roles of ß-PPARα and ß-HNF4α. Given that ß-HNF4α potently induces PPARα expression, we define a novel adiponectin-HNF4α-PPARα cascade. We further analyzed downstream genes consistently regulated by this axis. Among them, the islet amyloid polypeptide (IAPP) gene is an important target and accumulates in adiponectin KO mice. We propose a new mechanism of IAPP aggregation in type 2 diabetes through reduced adiponectin action.

Signaling Pathways Associated With Prior Cardiovascular Events in Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. A subset of patients experience major adverse cardiovascular events (MACEs), including arrhythmias, strokes and heart failure. However, the molecular mechanisms underlying MACEs in HCM are still not well understood. Therefore, we conducted a multicenter case-control study of patients with HCM, comparing those with and without prior histories of MACEs to identify dysregulated signaling pathways through plasma proteomics profiling. METHODS: We performed plasma proteomics profiling of 4986 proteins. We developed a proteomics-based discrimination model in patients enrolled at 1 institution (training set) and externally validated the model in patients enrolled at another institution (test set). We performed pathway analysis of proteins dysregulated in patients with prior MACEs. RESULTS: A total of 402 patients were included, with 278 in the training set and 124 in the test set. In this cohort, 257 (64%) patients had prior MACEs (172 in the training set and 85 in the test set). Using the proteomics-based model from the training set, the area under the receiver operating characteristic curve was 0.82 (95% confidence interval, 0.75-0.90) in the test set. Patients with prior MACEs demonstrated dysregulation in pathways known to be associated with MACEs (eg, TGF-ß) and novel pathways (eg, Ras-MAPK and associated pathways). CONCLUSIONS: In this multicenter study of 402 patients with HCM, we identified both known and novel pathways dysregulated in a subset of patients with more advanced disease.

Valvular Heart Disease Associated With Radiation Therapy: A Contemporary Review.

Valvular heart disease can develop as a long-term side effect of radiation therapy, along with other cardiovascular complications. The timeline until clinically significant disease can be on the order of decades, with left-sided valves most commonly affected. Only a few retrospective studies have characterized the incidence and findings associated with radiation therapy associated valvular heart disease. Furthermore, treatment can be difficult in this population given certain factors that can contribute to high surgical risk. In recent years, however, the development of transcatheter options for valvular disease has led to expanded eligibility criteria for cancer patients who may receive radiation therapy as part of their treatment course. We therefore sought to review the literature on radiation-induced valvular heart disease and provide an overview of recent studies on post-intervention outcomes in these patients.

Development of an eHealth Tool for Capturing and Analyzing the Immune-related Adverse Events (irAEs) in Cancer Treatment.

Introduction: Immunotherapy has revolutionized the treatment of many different types of cancer, but it is associated with a myriad of immune-related adverse events (irAEs). Patient-reported outcome (PRO) measures have been identified as valuable tools for continuously collecting patient-centered data and are frequently used in oncology trials. However, few studies still research an ePRO follow-up approach on patients treated with Immunotherapy, potentially reflecting a lack of support services for this population. Methods: The team co-developed a digital platform (V-Care) using ePROs to create a new follow-up pathway for cancer patients receiving immunotherapy. To operationalize the first 3 phases of the CeHRes roadmap, we employed multiple methods that were integrated throughout the development process, rather than being performed in a linear fashion. The teams employed an agile approach in a dynamic and iterative manner, engaging key stakeholders throughout the process. Results: The development of the application was categorized into 2 phases: "user interface" (UI) and "user experience" (UX) designs. In the first phase, the pages of the application were segmented into general categories, and feedback from all stakeholders was received and used to modify the application. In phase 2, mock-up pages were developed and sent to the Figma website. Moreover, the Android Package Kit (APK) of the application was installed and tested multiple times on a mobile phone to proactively detect and fix any errors. After resolving some technical issues and adjusting errors on the Android version to improve the user experience, the iOS version of the application was developed. Discussion: By incorporating the latest technological developments, V-Care has enabled cancer patients to have access to more comprehensive and personalized care, allowing them to better manage their condition and be better informed about their health decisions. These advances have also enabled healthcare professionals to be better equipped with the knowledge and tools to provide more effective and efficient care. In addition, the advances in V-Care technology have allowed patients to connect with their healthcare providers more easily, providing a platform to facilitate communication and collaboration. Although usability testing is necessary to evaluate the efficacy and user experience of the app, it can be a significant investment of time and resources. Conclusion: The V-Care platform can be used to investigate the reported symptoms experienced by cancer patients receiving Immune checkpoint inhibitors (ICIs) and to compare them with the results from clinical trials. Furthermore, the project will utilize ePRO tools to collect symptoms from patients and provide insight into whether the reported symptoms are linked to the treatment. Clinical Relevance: V-Care provides a secure, easy-to-use interface for patient-clinician communication and data exchange. Its clinical system stores and manages patient data in a secure environment, while its clinical decision support system helps clinicians make decisions that are more informed, efficient, and cost-effective. This system has the potential to improve patient safety and quality of care, while also helping to reduce healthcare costs.

Development and initial evaluation of a behavioural intervention to support weight management for people with serious mental illness: an uncontrolled feasibility and acceptability study.

BACKGROUND: The rates of obesity and associated health problems are higher in people with serious mental illness (SMI), such as schizophrenia and bipolar disorder, than the general population. A primary care referral to a behavioural weight management programme can be an effective intervention, but people with SMI have reported barriers to engaging with them and bespoke options are rarely provided in routine practice. It is possible that adjunct support addressing these specific barriers could help. Here we report the development, feasibility and acceptability of an intervention to improve uptake and engagement with a mainstream weight management programme for people with SMI. METHODS: We worked with people with a lived-experience of SMI and used the person-based approach to develop the 'Weight cHange for people with sErious mEntal iLlness' (WHEEL) intervention. It comprised a referral to a mainstream weight management programme (WW®) to be attended once a week, in-person or online, for 12-weeks. The adjunct support comprised a one-off, online consultation called Meet Your Mentor and weekly, telephone or email Mentor Check Ins for 12-weeks. We assessed the feasibility of WHEEL through the number of programme and adjunct support sessions that the participants attended. We analysed the acceptability of WHEEL using a thematic analysis of qualitative interviews conducted at baseline and at 12-week follow-up. Our exploratory outcome of clinical effectiveness was self-reported weight at baseline and at end-of-programme. RESULTS: Twenty participants were assessed for eligibility and 17 enrolled. All 17 participants attended Meet Your Mentor and one was lost to follow-up (94% retention). Nine out of 16 attended ≥50% of the weekly programme sessions and 12/16 attended ≥50% of the weekly check-ins. Participants reported in the interviews that the adjunct support helped to establish and maintain a therapeutic alliance. While some participants valued the in-person sessions, others reported that they preferred the online sessions because it removed a fear of social situations, which was a barrier for some participants. The mean change in self-reported weight was - 4·1 kg (SD: 3·2) at 12-weeks. CONCLUSIONS: A mainstream weight management programme augmented with brief and targeted education and low-intensity check-ins generated sufficient engagement and acceptability to warrant a future trial.

Depression, anxiety and post-traumatic stress during the 2022 Russo-Ukrainian war, a comparison between populations in Poland, Ukraine, and Taiwan.

Ukraine has been embroiled in an increasing war since February 2022. In addition to Ukrainians, the Russo-Ukraine war has affected Poles due to the refugee crisis and the Taiwanese, who are facing a potential crisis with China. We examined the mental health status and associated factors in Ukraine, Poland, and Taiwan. The data will be used for future reference as the war is still ongoing. From March 8 to April 26, 2022, we conducted an online survey using snowball sampling techniques in Ukraine, Poland, and Taiwan. Depression, anxiety, and stress were measured using the Depression, Anxiety, and Stress (DASS)-21 item scale; post-traumatic stress symptoms by the Impact of Event Scale-Revised (IES-R) and coping strategies by the Coping Orientation to Problems Experienced Inventory (Brief-COPE). We used multivariate linear regression to identify factors significantly associated with DASS-21 and IES-R scores. There were 1626 participants (Poland: 1053; Ukraine: 385; Taiwan: 188) in this study. Ukrainian participants reported significantly higher DASS-21 (p < 0.001) and IES-R (p < 0.01) scores than Poles and Taiwanese. Although Taiwanese participants were not directly involved in the war, their mean IES-R scores (40.37 ± 16.86) were only slightly lower than Ukrainian participants (41.36 ± 14.94). Taiwanese reported significantly higher avoidance scores (1.60 ± 0.47) than the Polish (0.87 ± 0.53) and Ukrainian (0.91 ± 0.5) participants (p < 0.001). More than half of the Taiwanese (54.3%) and Polish (80.3%) participants were distressed by the war scenes in the media. More than half (52.5%) of the Ukrainian participants would not seek psychological help despite a significantly higher prevalence of psychological distress. Multivariate linear regression analyses found that female gender, Ukrainian and Polish citizenship, household size, self-rating health status, past psychiatric history, and avoidance coping were significantly associated with higher DASS-21 and IES-R scores after adjustment of other variables (p < 0.05). We have identified mental health sequelae in Ukrainian, Poles, and Taiwanese with the ongoing Russo-Ukraine war. Risk factors associated with developing depression, anxiety, stress, and post-traumatic stress symptoms include female gender, self-rating health status, past psychiatric history, and avoidance coping. Early resolution of the conflict, online mental health interventions, delivery of psychotropic medications, and distraction techniques may help to improve the mental health of people who stay inside and outside Ukraine.

Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles.

AIMS: Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 h after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 min) release of extracellular vesicles (EVs), which have emerged as an important means of cell-cell signalling and are thus a potential mechanism for communicating with remote tissues. METHODS AND RESULTS: Here, we show that injury to the myocardium rapidly mobilizes neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to arrival at the injured tissue. Time course analysis of plasma-EV composition revealed a rapid and selective increase in EVs bearing VCAM-1. These EVs, which were also enriched for miRNA-126, accumulated preferentially in the spleen where they induced local inflammatory gene and chemokine protein expression, and mobilized splenic-neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing, we generated VCAM-1-deficient EC-EVs and showed that its deletion removed the ability of EC-EVs to provoke the mobilization of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model. CONCLUSIONS: Our findings show a novel EV-dependent mechanism for the rapid mobilization of neutrophils to peripheral blood from a splenic reserve and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells.

Childhood Acid Suppressants May Increase Allergy Risk-A Systematic Review and Meta-Analysis.

BACKGROUND: Recent studies suggest that the use of acid suppressants in early childhood may increase the risk of allergic diseases. OBJECTIVE: To systematically review and synthesize associations between the childhood use of acid suppressants and development of allergic diseases. METHODS: PubMed, Embase, The Cochrane Library, and Scopus were searched using a systematic search strategy. We included observational or interventional studies that looked at the use of acid suppressants in the pediatric population, in association with allergic outcomes such as asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and food allergies. Key data were extracted and risk of bias was evaluated according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and a PROSPERO-registered protocol. Maximally adjusted estimates were pooled using mixed-effects models, and heterogeneity was measured using I2. Further subgroup and sensitivity analyses were conducted. Overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework. RESULTS: This review included 5 observational studies from 1977 records with low-to-moderate risk of bias. Childhood acid-suppressant use was associated with significantly increased hazards of asthma (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.31-1.58), atopic dermatitis (HR = 1.12, 95% CI = 1.10-1.14), and allergic rhinitis (HR = 1.40, 95% CI = 1.24-1.58). These associations were adjusted for confounders such as demographics, parental educational level, and use of antibiotics. Overall quality of evidence was low. CONCLUSIONS: Childhood use of acid suppressants may increase the risk of incident asthma, atopic dermatitis, and allergic rhinitis. However, larger studies such as randomized controlled trials are needed to determine causality. These drugs should be used judiciously in pediatric patients, and more stringent guidelines should be advocated.

The effectiveness of psychoeducational interventions on caregiver-oriented outcomes in caregivers of adult cancer patients: A systematic review and meta-analysis.

OBJECTIVE: Cancer caregiving can result in increased psychosocial distress and poor health-related quality of life (QOL). Psychoeducation has been shown to be effective in enhancing caregiving-oriented outcomes. A systematic assessment of the overall effect of psychoeducational intervention (PEI) and identification of individual intervention characteristics that may contribute to the effectiveness of PEI is needed. METHODS: For this meta-analysis, relevant articles were identified through electronic databases using key search terms and their medical subject heading such as "family caregiver," "cancer," and "psychoeducational intervention." RESULTS: Twenty-eight controlled trials with 3876 participants were included. PEIs had beneficial effect on depression (Standardized Mean Difference [SMD] -0.26; 95% CI = -0.50 to -0.01, p < 0.04), anxiety (SMD -0.41; 95% CI = -0.82 to 0.01, p < 0.05), caregiver burden (SMD -0.84; 95% CI = -1.22 to -0.46, p < 0.0001) and QOL (SMD 0.59, 95% CI 0.24-0.93; p < 0.0009) at the immediate post-intervention period. At longer-term follow-up, the effectiveness of PEI was maintained on QOL (SMD 0.39, 95% CI = -0.00 to -0.77, p < 0.05), and anxiety (SMD -0.57; 95% CI = -1.09 to -0.06, p < 0.03). Moderation analysis showed that intervention characteristics such as studies conducted in high-income countries, group intervention and studies that focused on specific and mixed cancers explain some of the high variations observed among the included studies. CONCLUSIONS: PEI may benefit caregivers of cancer patients through the significant effects on caregiver burden, QOL, anxiety, and depression. The findings from the moderation analysis may be important for the design of future interventions.

Barriers to abortion provision in primary care in New England, 2019-2020: A qualitative study.

OBJECTIVE: To assess barriers to and facilitators of abortion provision among abortion-trained primary care providers. STUDY DESIGN: We conducted 21 qualitative in-depth interviews with 20 abortion-trained family physicians and one internal medicine physician in five New England states. We dual-coded interviews, using a consensus method to agree upon final coding schema. Through iterative dialogue, using an inductive content analysis approach, we synthesized the themes and identified patterns within each domain of inquiry. RESULTS: The most commonly reported barriers were a lack of organizational support, the Hyde Amendment, which prevents the use of federal funds for most abortion care, and the mifepristone Risk Evaluation and Mitigation Strategy, a federal regulation which prohibits routine mifepristone pharmacy dispensing. The logistical barriers created by these policies require cooperation from additional stakeholders, creating more opportunities for abortion stigma and moral opposition to arise. Other salient barriers included inter-specialty tension (particularly with obstetrician-gynecologists), perceived need for pre-abortion ultrasound, absence of a clinician support network, and lack of knowledge of existing resources for establishing abortion care in primary care. CONCLUSIONS: Increased abortion provision in primary care is one of many necessary responses to the human rights crisis produced by the Dobbs decision. Eliminating the Hyde Amendment and ending federal regulations restricting pharmacy dispensing of mifepristone are key interventions to address barriers to primary care abortion provision. Building interspecialty partnerships between family medicine and OB/GYN and spreading awareness of the evidence-based ultrasound-as-needed protocol and other educational resources are also likely to increase primary care abortion access. IMPLICATIONS: By exploring barriers to and facilitators of primary care abortion provision, this study outlines a targeted approach to support increased access to abortions. In states with legal abortion post-Roe, it is important that motivated and trained primary care providers can offer abortions, rather than referring patients to overburdened specialty clinics.

Immigrants' and refugees' experiences of access to health and social services during the COVID-19 pandemic in Toronto, Canada.

OBJECTIVE: In 2020, the World Health Organization reported that immigrants were the most vulnerable to contracting COVID, due to a confluence of personal and structural barriers. This study explored how immigrants and refugees experienced access to health and social services during the first wave of COVID-19 in Toronto, Canada. METHODS: This study analyzed secondary data from a qualitative study that was conducted between May and September 2020 in Toronto that involved semi-structured interviews with 72 immigrants and refugees from 21 different countries. The secondary data analysis was informed by critical realism. RESULTS: The vast majority of participants experienced fear and anxiety during the COVID-19 outbreak but through a combination of self-reliance and community support came to terms with the realities of the pandemic. Some even found the lifestyle changes engendered by the pandemic a positive experience. CONCLUSIONS: Self-reliance may hinder help-seeking and augment the threat of COVID-19. This is particularly a concern for the most vulnerable immigrants, who experience multiple disruptions in their health care, have limited material resources and social supports, and perhaps are still dealing with the challenges of settling in the new country.

Spatial intra-tumor heterogeneity is associated with survival of lung adenocarcinoma patients.

Intra-tumor heterogeneity (ITH) of human tumors is important for tumor progression, treatment response, and drug resistance. However, the spatial distribution of ITH remains incompletely understood. Here, we present spatial analysis of ITH in lung adenocarcinomas from 147 patients using multi-region mass spectrometry of >5,000 regions, single-cell copy number sequencing of ~2,000 single cells, and cyclic immunofluorescence of >10 million cells. We identified two distinct spatial patterns among tumors, termed clustered and random geographic diversification (GD). These patterns were observed in the same samples using both proteomic and genomic data. The random proteomic GD pattern, which is characterized by decreased cell adhesion and lower levels of tumor-interacting endothelial cells, was significantly associated with increased risk of recurrence or death in two independent patient cohorts. Our study presents comprehensive spatial mapping of ITH in lung adenocarcinoma and provides insights into the mechanisms and clinical consequences of GD.