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Rationale & Objective: Formalized peer support is a promising approach for addressing the emotional and practical needs of people living with chronic kidney disease (CKD). We systematically identified and summarized peer support interventions studied in individuals with CKD with or without kidney replacement therapy (KRT)., Sources of Evidence: Search of electronic databases and grey literature sources in March 2023., Eligibility Criteria: Studies of any design were eligible if they reported sufficient detail on peer support interventions and outcomes for adults with CKD with or without KRT and/or their caregivers., Charting Methods: We extracted information on study and intervention characteristics and reported outcomes using established frameworks. We summarized quantitative data descriptively and qualitative data thematically. Our approach observed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews., Results: We included 77 studies describing 56 unique peer support interventions. Most reports were program evaluations (39%) or randomized controlled trials (27%) published after 2013. Two-thirds of interventions focused on in-center hemodialysis or mixed CKD populations, and three quarters were integrated within a kidney care clinic or program. Whereas most peer interactions centered on informational support, few programs offered focused support in areas such as transplant navigation or dialysis modality selection. Only one-third of outcomes were assessed against a comparator group, with results suggesting improvements in psychological health with peer support., Limitations: Heterogeneity of included studies; lack of rigorous program evaluation., Conclusions: This review suggests recent growth in peer support programming with a variety of formats and delivery methods to address the diverse needs of people living with kidney disease. Notable gaps in peer support availability for transplant and home dialysis recipients and the lack of rigorous evaluations present opportunities to expand the reach and impact of peer support in the kidney care context., Plain-Language Summary: Many people with kidney disease struggle with isolation, making decisions about their care, and declines in their mental well-being. Peer support is a way of providing information and emotional support to patients and their loved ones by connecting them with others who have a shared experience of kidney disease. We summarize the features of peer support programs worldwide and the settings in which they have been studied. We searched the medical literature and found 56 unique peer support programs reported in 77 studies. Most studies were from the last 10 years, targeted people receiving hemodialysis, and focused on sharing information about kidney disease. Studies summarized in this review revealed notable gaps in peer support availability for transplant and home dialysis recipients. Many studies found improvements in people's mental health, quality of life, and confidence in managing their health after initiation of peer support. These findings suggest there are unrealized opportunities to expand the reach and impact of peer support in the care of patients with kidney disease., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Public safety personnel (PSP), such as police officers, firefighters, correctional workers, and paramedics, routinely face work stressors that increase their risk of developing posttraumatic stress disorder (PTSD). PSP may additionally face moral transgressions in the workplace (e.g., witnessing human suffering, working within broken systems), heightening the risk of moral injury (MI) in this population. Research among military personnel and health care workers shows an association between MI and PTSD; however, less is known about the association between these constructs among PSP. Canadian PSP completed an online survey between June 2022 and June 2023, including a demographic questionnaire and measures of PTSD, MI, dissociation, depression, anxiety, stress, and childhood adversity. Latent variable structural equation modeling (SEM) was performed to ascertain the impact of a latent MI construct (i.e., shame, trust violation, functional impairment) on a latent PTSD construct (i.e., intrusions, avoidance, negative alterations in cognition and mood, hyperreactivity, depersonalization, derealization). Sex, age, depression, anxiety, stress, and childhood adversity were included as covariates. A total of 314 PSP were included in the data analysis. A latent variable SEM regressing PTSD onto MI and including covariates accounted for 83.7% of the variance in PTSD. MI was the strongest predictor compared to all covariates and was significantly associated with PTSD symptoms, β = .506, p < .001, above and beyond the impacts of sex, age, depression, anxiety, stress, and childhood adversity. These findings are consistent with research among military members and health care providers and highlight the importance of further exploring MI among PSP., (© 2024 The Author(s). Journal of Traumatic Stress published by Wiley Periodicals LLC on behalf of International Society for Traumatic Stress Studies.)

Anticoagulant use is prevalent and associated with significant potential for harm. Anticoagulation stewardship practice has emerged to address care gaps and promote safe, effective, and cost-conscious anticoagulation use across health care systems. Here we present 4 patient cases describing common challenges in anticoagulation management: inappropriate dosing of direct oral anticoagulants (DOACs), the diagnosis and management of heparin-induced thrombocytopenia (HIT), periprocedural anticoagulation management, and heavy menstrual bleeding on anticoagulation. We discuss available examples of successful stewardship programs that can address the challenges of each case, demonstrating how an investment in anticoagulation stewardship can improve patient outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Patients who present with urinary tract infections secondary to obstructing stones occasionally fail to improve on treatment based on midstream urine culture (MUSCx). Varying microbiomes between the bladder and the renal pelvis may account for this. In this study, we sought to investigate the utility of obtaining a renal pelvis urine culture (RPUCx) at the time of stenting to guide antibiotic treatment prior to definitive stone operation. Materials and Methods: RPUCx was obtained in 257 patients presenting with obstructive ureteral stones undergoing emergent stenting. Concordance rates of RPUCx to MUSCx and blood cultures were examined. Operative time and infectious complication rates after definitive stone management between the two groups were studied. A comparison of those who received an intraoperative RPUCx with those who did not was carried out. Results and Conclusions: RPUCx was obtained in patients undergoing emergent stenting from 2018 to -2021; 31% (52/168) of patients had pathogens in the renal pelvis that were absent in the MUSCx. RPUCx had a greater concordance rate with blood culture results compared with MUSCx (95% vs 50%). Drawing RPUCx intraoperatively did not significantly change operative time (15.9 vs 13.6 minutes, p = 0.15). Treatment tailored to RPUCx resulted in lower rates of post-stone management complications (odds ratio 0.26, 95% confidence interval = 0.08-0.83; p = 0.01). RPUCx at the time of stenting can guide treatment and decrease post-treatment complications without additional operative time, confirming utility in the treatment of patients with infection secondary to obstructing stones.

Infections caused by the airborne fungal pathogen, Aspergillus fumigatus, are increasing in severity due to growing numbers of immunocompromised individuals and the increasing incidence of antifungal drug resistance, exacerbating treatment challenges. Gallium has proven to be a strong candidate in the fight against microbial pathogens due to its iron-mimicking capability and substitution of Ga(III) in place of Fe(III), disrupting iron-dependent pathways. Since the antimicrobial properties of 2,2'-bipyridine and derivatives have been previously reported, we assessed the in vitro activity and proteomic effects of a recently reported heteroleptic Ga(III) polypyridyl catecholate compound against A. fumigatus. This compound has demonstrated promising growth-inhibition and impact on the A. fumigatus proteome compared to untreated controls. Proteins associated with DNA replication and repair mechanisms along with lipid metabolism and the oxidative stress responses were elevated in abundance compared to control. Crucially, a large number of mitochondrial proteins were reduced in abundance. Respiration is an important source of energy to fuel metabolic processes required for growth, survival and virulence, the disruption of which may be a viable strategy for the treatment of microbial infections., Competing Interests: Declarations. Conflict of interest: There are no conflicts to declare. Ethical approval: Not required. Consent for publication: Not relevant., (© 2024. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

Introduction: "Subureteric Teflon INGection" (STING) of polytetrafluoroethylene (PTFE/polytef) paste to treat vesicoureteral reflux (VUR) in children was popularised in 1984. It was later abandoned as an implantation material because of the possibility of migration from the injection site. Giant-cell foreign-body granuloma to Polytef in the bladder is a rare cause of ureteric obstruction. Only a handful of cases have been reported in the literature., Methods: We performed a prospective analysis of a series of 6 adult patients who had childhood STING and presented with foreign-body granuloma to Polytef in the bladder. We report their clinical presentation, findings and treatment., Results: 1 male and 5 females with a history of STING procedure in childhood for VUR presented in later life with foreign-body granuloma to Polytef. The median age at first STING procedure and at presentation to the Urology Department was 3 and 34 years respectively. The most common clinical presentations were flank pain and urinary tract infection (UTI) and all patients had radiological findings of calcified lesions at the vesicoureteric junction(s). 4 patients had histological findings of giant-cell foreign-body granuloma. 4 patients required definitive ureteric reimplantation., Conclusion: Polytef granuloma causing distal ureteric obstruction may give rise to significant morbidity and renal damage. Due to the likelihood of progression of the granuloma, excision and ureteric reimplantation is considered the standard approach in the management of patients with viable kidneys., Level of Evidence: Level 5., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Objectives: Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP., Methods: We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death., Results: We identified 49 eligible studies reporting 112 critical bleed patients with ITP, including 66 children (median age, 10 years), 36 adults (median age, 41.5 years), and 10 patients with unreported age. Patients received corticosteroids (n = 67), IVIG (n = 49), platelet transfusions (n = 41), TPO-RAs (n = 17), and splenectomy (n = 28) either alone or in combination. Studies reported 29 different treatment combinations, the 5 most common were corticosteroids, platelet transfusion and splenectomy (n = 13), corticosteroids and IVIG (n = 13), or splenectomy alone (n = 13); IVIG alone (n = 11); and corticosteroids, IVIG and TPO-RA (n = 8). Mortality among patients with critical bleeds in ITP was 30.6% for adults and 19.7% for children., Conclusions: The effects of individual treatments on patient outcomes were uncertain due to very low-quality evidence. There is a need for a standardized approach to the treatment of ITP critical bleeds., Systematic Review Registration: CRD42020161206., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Aims and Method: Higher specialist trainees (HSTs) in psychiatry in Ireland were recruited to complete a 21-item online questionnaire anonymously. Questions were designed to establish the research experience of HSTs in various years of training, identify perceived barriers to participation and generate potential strategies to overcome these barriers., Results: Of 165 HSTs surveyed, 50 (30%) responded. Most respondents (58%) were in the second or third year of HST. Most (72%) were training in general adult psychiatry. Themes that emerged from analysis of the qualitative data were 'collaborative research culture', 'guidance', 'choice' and 'access to resources'. Participants felt they needed more structured guidance and regular supervision, and expressed a desire for more networking and collaboration., Clinical Implications: The need for a supportive, collaborative research culture within psychiatry was predominant among responses. Structured research programmes and access to resources may facilitate a more positive research culture and should be considered as part of the training curriculum.

Introduction: Twin pregnancies are associated with significantly higher perinatal mortality (PM) rates compared to singletons, primarily due to complications like fetal growth restriction, preterm birth, and congenital anomalies. This study aimed to compare the characteristics associated with PM in twin pregnancies and compare maternal and obstetric factors and cause of death among twins and singletons in the Republic of Ireland., Materials and Methods: Data spanning 2011 to 2022 from the National Perinatal Epidemiology Centre's annual perinatal mortality clinical audit included 4494 perinatal deaths. Maternal characteristics, antenatal care factors and cause of death were analysed with relative risk calculated using national Hospital In-Patient Enquiry data. Pearson's chi-squared tests studied the difference between mortality in twins and singletons., Results: Twins accounted for 10.4% of all perinatal deaths, despite representing only 3.6% of total births. The PM rate for twins was 17.3 per 1000 births, 3.1 times higher than for singletons. Early neonatal deaths (ENNDs) were more frequent in twins (54.2%), while stillbirths predominated among singletons (68.6%). Younger maternal age and lower BMI were associated with higher PM risks in twins. A considerable proportion of twin deaths with major congenital anomalies or birth before 28 weeks gestation occurred in non-tertiary hospitals, suggesting limitations in referral pathways to centres with appropriate neonatal expertise., Conclusion: Twin pregnancies pose a higher risk of perinatal mortality, particularly among younger mothers and preterm births. The findings highlight the need for updated guidelines that prioritise early risk assessment, targeted interventions, and improved referral systems., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Over the past decade, the field of heart failure (HF) has witnessed remarkable progress in drug development, resulting in the approval of numerous groundbreaking drugs by the U.S. Food and Drug Administration. To address some of these challenges, the U.S. Food and Drug Administration has issued guidance documents that have been critical in contemporary HF drug development; however, there are still many challenges in need of investigation. This paper leverages efforts of the Heart Failure Collaboratory and the scientific community to discuss the critical need for innovative trial designs, important concepts in clinical trials in the modern era, and the utilization of big data to accelerate HF drug development. At this inflection point in HF drug development, it is imperative that, as a global scientific community, we foster increased collaboration among researchers, clinicians, patients, and regulatory bodies. Only through such unified efforts can we navigate the complexities of HF, accelerate the development process, and ultimately deliver effective therapies that transform patient outcomes., Competing Interests: Funding Support and Author Disclosures Dr Januzzi has a board position with Imbria Pharma; has received grant support from Abbott, Applied Therapeutics, AstraZeneca, BMS, and Novartis Pharmaceuticals; has received consulting income from Abbott Diagnostics, Beckman-Coulter, Jana Care, Janssen, Novartis, Prevencio, Quidel, and Roche Diagnostics; and has served on clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, CVRx, Medtronic, Pfizer, and Roche Diagnostics. Dr Lindenfeld has received consulting fees from Abbott, Adona, Axon, Alleviant, AstraZeneca, Boston Scienrific, CVRx, Cordio, Edwards Lifesciences, Medtronic, Merck, Orchestra Biomed, VWave, Whiteswell, and Vascular Dynamics; and has received grant funding from AstraZeneca and Volumetrix. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Bristow has been a consultant for ARCA Biopharma. Dr Abraham has received research grant support from the NHLBI (NIH 1 UG3/UH3 HL140144-01, 08/01/18-07/31/22, “Impact of Low Flow Nocturnal Oxygen Therapy on Hospital Readmission/Mortality in Patients with Heart Failure and Central Sleep Apnea [LOFT-HF]”); has received consulting income from Abbott Vascular, Boehringer Ingelheim, and Zoll Respicardia; has received speaker honoraria from Impulse Dynamics; and has received salary support from V-Wave Medical. Dr O'Connor has done consulting for Abiomed and Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF. The effect of vericiguat in patients with HFrEF without recent worsening HF remains unknown. The VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial was designed to assess the efficacy and safety of vericiguat in patients with ejection fraction ≤40% without recent worsening HF on a background of current foundational HFrEF therapy., Methods: The primary endpoint for VICTOR is time to first event for the composite of HHF or cardiovascular death. The trial will also assess the effect of vericiguat on time to cardiovascular death, time to HHF, total HHF, and all-cause death. As an event-driven trial, at least 1080 primary events are expected, but follow-up will continue until the targeted number of at least 590 cardiovascular deaths has been reached. Approximately 6000 participants will be randomized to vericiguat or placebo., Conclusion: VICTOR is the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational guideline-directed medical therapy, in a compensated ambulatory HF population. VICTOR will add important information to the evidence of the effects of vericiguat across the spectrum of patients with HFrEF., (© 2024 Bayer AG, Merck Sharp & Dohme LLC and The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Major knowledge and practice gaps exist in aged care home services to support independence of older people with dementia. This research evaluates an adaptation of a community-based rehabilitation model for care homes, namely Interdisciplinary Care Home-bAsed Reablement Program (I-CHARP), by examining whether (and, if so, how) I-CHARP produces its intended effects and how this programme can be practicably implemented, sustained and scaled up across care homes in Australia., Methods: I-CHARP is a 4-month bio-behavioural-environmental rehabilitation model of care, integrated in care home services, supported through the deployment of an implementation strategy, the Research Enabled Aged Care Homes (REACH) network. It consists of (1) 8-12 full individual sessions and additional eight brief follow-ups per resident, tailored to the resident's needs, delivered primarily by a team of an occupational therapist, registered nurse and other allied health staff; (2) environmental modifications/assistive devices up to the value of $400 per resident; and (3) engagement of intervention care home staff, managers and regular visitors. An overarching evaluation approach is participatory action research using a cluster quasi-experimental design and mixed methods. It involves testing of the implementation strategy (REACH network and other approaches) while observing/gathering information on the intervention (I-CHARP) and related outcomes in three cycles. Participants include residents (aged ≥ 60 years with early stages of dementia) and care staff from 16 care homes. Care quality indicators, health care costs, field notes and semi-structured interviews/focus groups with intervention site staff, regular visitors and managers will provide further insights into I-CHARP processes and implementation issues., Discussion: In the final phase of the project, an Agile Implementation Playbook will be developed for the delivery of reablement care that can be used in routine practice across care homes in Australia. The study findings will also inform future policy development and strategic directions for dementia care in care homes., Trial Registration: Australian New Zealand Clinical Trial Registry, ACTRN12623000885695 Registered 16 August 2023, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386088., Protocol Version: 1.0 dated 20 July 2023., (© 2024 John Wiley & Sons Ltd.)

The extracellular matrix plays a critical role in modulating cell behaviour in the developing and adult central nervous system influencing neural cell morphology, function and growth. Neurons and astrocytes, play vital roles in neural signalling and support respectively and respond to cues from the surrounding matrix environment. However, a better understanding of the impact of specific individual extracellular matrix proteins on both neurons and astrocytes is critical for advancing the development of matrix-based scaffolds for neural repair applications. This study aimed to provide an in-depth analysis of how different commonly used extracellular matrix proteins- laminin-1, Fn, collagen IV, and collagen I-affect the morphology and growth of trophic induced pluripotent stem cell (iPSC)-derived astrocyte progenitors and mouse motor neuron-like cells. Following a 7-day culture period, morphological assessments revealed that laminin-1, fibronectin, and collagen-IV, but not collagen I, promoted increased process extension and a stellate morphology in astrocytes, with collagen-IV yielding the greatest increases. Subsequent analysis of neurons grown on the different extracellular matrix proteins revealed a similar pattern with laminin-1, fibronectin, and collagen-IV supporting robust neurite outgrowth. fibronectin promoted the greatest increase in neurite extension, while collagen-I did not enhance neurite growth compared to poly-L-lysine controls. Super-resolution microscopy highlighted extracellular matrix-specific nanoscale changes in cytoskeletal organization, with distinct patterns of actin filament distribution where the three basement membrane-associated proteins (laminin-1, fibronectin, and collagen-IV) promoted the extension of fine cellular processes. Overall, this study demonstrates the potent effect of laminin-1, fibronectin and collagen-IV to promote both iPSC-derived astrocyte progenitor and neuronal growth, yielding detailed insights into the effect of extracellular matrix proteins on neural cell morphology at both the whole cell and nanoscale levels. The ability of laminin-1, collagen-IV and fibronectin to elicit strong growth-promoting effects highlight their suitability as optimal extracellular matrix proteins to incorporate into neurotrophic biomaterial scaffolds for the delivery of cell cargoes for neural repair., (© 2024 The Author(s). Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Background: Adjuvant mFOLFIRINOX (mFFX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). There are limited data on adjuvant mFFX outcomes outside clinical trials., Methods: Institutional databases queried to identify patients with resected PDAC who received ≥1 dose adjuvant mFFX. Primary endpoints: recurrence free survival (RFS), overall survival (OS). Secondary endpoints: clinical factors, genomic features associated with outcomes. RFS and OS were estimated with Kaplan-Meier. Cox proportional hazards regression model was used to associate clinico-genomic features correlated with survival outcomes., Results: N = 147 identified between 01/2015-01/2023. Median age: 67 years; N = 57 (39%) >70 years. Unfavorable prognostic features: N = 52 (36%) N2 nodal status, N = 115 (78%) lymphovascular invasion), and N = 133 (90%) perineural invasion. Median time from surgery to start mFFX: 1.78 months (m) (IQR 1.45, 2.12). N = 124 (84%) completed 12 doses; N = 98 (67%) stopped oxaliplatin early for neuropathy (median 10 doses; range 4-12). Further dosing characteristics are summarized in Supplementary Table 3. With median follow up of 35.1 m, median RFS (mRFS) 26 m (95% CI 19, 39) and median OS (mOS) not reached. For >70 cohort, mRFS 23 m (95% CI 14, NR) and mOS 51 m (95% CI 37, NR). mFFX started <8 weeks from resection associated with improved RFS (HR 0.62; 95% CI 0.41, 0.96; p = .033) and OS (HR 0.53; 95% CI 0.3, 0.94; p = .030). KRAS mutation and whole genome doubling trended to shorter RFS and OS. Homologous recombination deficiency status did not confer improved survival outcomes., Conclusions: Adjuvant mFFX is effective and tolerable in resected PDAC in a non-trial setting, including for patients >70 years., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Managing skin conditions in patients with darkly pigmented skin (DPS) can be challenging due to inadequate exposure to dermatology in DPS in clinical training. In this study, Irish GPs were less likely to correctly diagnose common skin conditions in patients with DPS ( p  < 0.001) and had lower confidence levels in diagnosis in DPS ( p  < 0.001). Lower diagnostic accuracy and confidence with common skin conditions in DPS in primary care may lead to misdiagnosis, suboptimal treatment and increased referrals to dermatology., Competing Interests: None to declare., (© 2024 The Author(s). Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Retinoic acid is crucial for vertebrate embryogenesis, influencing anterior-posterior patterning and organogenesis through its interaction with nuclear hormone receptors comprising heterodimers of retinoic acid receptors (RARα, β, or γ) and retinoid X receptors (RXRα, β, or γ). Tissue retinoic acid levels are tightly regulated since both its excess and deficiency are deleterious. Dehydrogenase/reductase 3 (DHRS3) plays a critical role in this regulation by converting retinaldehyde to retinol, preventing excessive retinoic acid formation. Mutations in DHRS3 can result in embryonic lethality and congenital defects. This study shows that mouse Dhrs3 expression is responsive to vitamin A status and is directly regulated by the RAR/RXR complex through cis-regulatory elements. This highlights a negative feedback mechanism that ensures retinoic acid homeostasis., (© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Competing Interests: Conflicts of interest J.M. is Editor-in-Chief of the BJD; E.A.O’T. is on the BJD’s Editorial Advisory Board. The other authors declare no conflicts of interest.

Study Objectives: This study aimed to outline the strategy and outcomes of a study team in recruiting participants for an infant sleep study via social media during the COVID-19 pandemic, to assess the feasibility of recruitment via social media, and to quantitatively and qualitatively explore parental satisfaction and perceptions of recruitment via social media., Methods: The assessing sleep in infants with early-onset atopic dermatitis by longitudinal evaluation (SPINDLE) study recruited infants with and without atopic dermatitis for a longitudinal study assessing sleep. Infants were recruited via social media and their parents were interviewed to explore their experience of recruitment via social media., Results: In total, 57 controls and 33 cases were recruited. Of the 45 controls recruited via social media, 43 (95.6%) were recruited via Instagram and 2 (4.4%) were recruited via Twitter. Of the seven cases recruited via social media, 6 (85.7%) were recruited via Facebook (via sharing of Instagram posts by third parties on Facebook) and 1 (14.3%) was recruited via Instagram. All (100%, n  = 28) mothers recruited via social media who completed the full study were satisfied with this approach to recruitment. Specific reasons why mothers reported engaging following exposure to the social media posts included the benefit of additional health checks for their baby, the benefit to scientific advancement, and the opportunity for a stimulating outing following the COVID-19 lockdowns., Conclusions: Our experience highlights parents' acceptance of recruitment via social media, the optimization of time and financial resources, and the benefit of using internet-based recruitment during a pandemic., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

The study of intellectual humility (IH), which is gaining increasing interest among cognitive scientists, has been dominated by a focus on individuals. We propose that IH operates at the collective level as the tendency of a collective's members to attend to each other's intellectual limitations and the limitations of their collective cognitive efforts. Given people's propensity to better recognize others' limitations than their own, IH may be more readily achievable in collectives than individuals. We describe the socio-cognitive dynamics that can interfere with collective IH and offer the solution of building intellectually humbling environments that create a culture of IH that can outlast the given membership of a collective. We conclude with promising research directions., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the safety, efficacy, and tolerability of gepirone (Exxua) in the treatment of adult patients with major depressive disorder. Data Sources: A literature search was performed through PubMed, Embase, and PsycINFO using the following terms: Exxua, gepirone, depression, major depressive disorder, anxiety, and anxiety disorders. Study Selection and Data Extraction: Articles that were selected included English-language dominant studies, or studies that could be translated into English by the authors, with terms associated with the safety, efficacy, and/or tolerability of gepirone. Data Synthesis: Gepirone exhibits its antidepressant activity through agonism of 5HT 1A serotonin receptors. Phase 3 clinical trials showed that gepirone at a dose of 20 to 80 mg was proven to be effective in the treatment of major depressive disorder in adult patients. Common adverse effects reported in clinical trials included dizziness, nausea, headache, fatigue, and insomnia. Conclusion: This review evaluates the pharmacokinetic, pharmacologic, efficacy, and safety profile of gepirone and includes a discussion on its place in therapy for the treatment of major depressive disorder. Most clinical guidelines recommend second-generation antidepressants consisting of selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors as first-line therapy options. Gepirone is expected to receive greater clinical relevance and recommendations when compared to other azapirone medications (buspirone) within practice guidelines. Gepirone could be considered as either an alternative option for patients failing first-line therapies or for initial use to avoid unwanted side effects of other therapy options in the treatment of adult patients with major depressive disorder., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The early components of the pupillary light reflex (PLR) are governed by the parasympathetic nervous system. The use of cheap, portable pupillometry devices may allow for the testing of parasympathetic-system health in field settings. We examined the reliability of two portable instruments for measuring the PLR and their sensitivity to individual differences known to modulate the PLR. Parameters of the PLR were measured in a community sample ( N = 108) in a variety of field settings. Measurements were taken using a commercial pupillometer (NeuroLight, IDMED) and an iPhone using the Reflex Pro PLR analyser (Brightlamp). The parameters of baseline pupil diameter, constriction latency, amplitude and relative amplitude of constriction, and constriction velocity were measured. Individual differences related to age, levels of anxiety, and post-traumatic stress disorder (PTSD) symptomology were assessed. Some measures could not be attained using the iPhone under these field conditions. The reliability of the measures was high, save for the measurement of contraction latency which was particularly unreliable for the iPhone system. The parameters of the PLR showed the same internal relationships as those established in laboratory-based measurements. Age was negatively correlated with all the reliable PLR parameters for both systems. Effects of anxiety and PTSD symptomology were also apparent. The study demonstrated that a hand-held portable infrared pupillometer can be used successfully to measure the PLR parameters under field settings and can be used to examine individual differences. This may allow these devices to be used in workplaces, sports fields, roadsides, etc., to examine parasympathetic activity where needed.

Introduction: People with dementia of all ages have a human right to equal access to quality health care. Despite evidence regarding its effectiveness, many people living with dementia are unable to access rehabilitation for promoting function and quality of life. Conducted in Australia, this study was designed to (1) explore barriers to access to dementia rehabilitation and (2) identify solutions that improve access to rehabilitation., Methods: People living with dementia (n = 5) and care partners (n = 8) and health professionals (n = 13) were recruited nationally. Experience-based codesign across three virtual workshops was used to understand barriers and design solutions to improve access to rehabilitation treatments. Socio-ecological analyses, using the Levesque Access to Health care framework, were applied to findings regarding barriers and to aid selection of solutions., Results: There was high attendance (92.3%) across the three workshops. Barriers were identified at a user level (including lack of knowledge, transport, cost and difficulty navigating the health, aged care and disability sectors) and health service level (including health professional low dementia knowledge and negative attitudes, inequitable funding models and non-existent or fragmented services). Solutions focused on widespread dementia education and training, including ensuring that people with dementia and their care partners know about rehabilitation therapies and that health professionals, aged care and disability co-ordinators know how to refer to and deliver rehabilitation interventions. Dementia care navigators, changes to Australia's public funding models and specific dementia rehabilitation programmes were also recommended., Conclusions: Barriers to accessing rehabilitation for people with dementia exist at multiple levels and will require a whole-community and systems approach to ensure change., Patient or Public Contribution: People with living experience (preferred term by those involved) were involved at two levels within this research. A Chief Investigator living with dementia was involved in the design of the study and writing of the manuscript. People with living experience, care partners and service providers were participants in the codesign process to identify barriers and design potential solutions., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe's interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga 2 (L4) 3 ] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

COVID-19 was a novel stressor that gave rise to pandemic related anxiety and increased the risk of mental health issues, particularly in youth. It is important to understand how such events contribute to psychological distress in young people to adequately intervene in the aftermath and to plan for future similar events. Using cross-sectional data from the CoSPACE Ireland study dataset this paper reports on the predictive relationship between COVID-19 anxiety and psychological distress for Irish adolescents ( N  = 314, M  = 14.05, SD  = 2.7, 11-18 years), while controlling for other influencing factors across multiple levels of a bioecological systems approach. Covariates were age, gender, ethnicity, social economic status, Peer Support, School Support and Parent-Child Closeness. Findings indicate that COVID-19 anxiety was a significant predictor of adolescents' psychological distress. Specifically, Consequence Anxiety (worries about the indirect consequences of COVID-19) was found to be a predictor of adolescents' psychological distress rather than Disease Anxiety (worries about the COVID-19 virus itself). Individual factors (e.g., age, ethnicity, special educational needs) and microsystem factors (e.g., parent child closeness, peer support) were also found to impact on adolescents' levels of psychological distress. A significant moderation analysis revealed that greater parent-child closeness reduced the strength of the positive association between Consequence Anxiety and psychological distress. These findings suggest that strategies to alleviate adolescents' psychological distress during pandemics should focus on reducing pandemic-related anxiety, specifically Consequence Anxiety. A multisystemic approach is also recommended to reduce the negative mental health impacts of the pandemic on adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 McMahon, Gallagher, Dowling, Donnellan, Houghton, Ryan, O’Connor and Walsh.)

Climate change is no longer a problem for future generations and the impact is already taking a toll in many parts of the world. Climate change has already caused substantial, and increasingly irreversible, damage to ecosystems. All these issues combined will inevitably lead to an increase in human suffering and forced displacement. This has significant ramifications for health care systems. In this editorial we outline how climate change is already impacting both physical and mental health. Health professionals have a role to play in addressing this great challenge of our time. Health professionals should reflect on how to promote means of climate change mitigation and adaptation within their spheres of influence - clinical, education, advocacy, administration, and research.

Science is humanity's best insurance against threats from nature, but it is a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates a natural origin for SARS-CoV-2. Yet, the theory that SARS-CoV-2 was engineered in and escaped from a lab dominates media attention, even in the absence of strong evidence. We discuss how the resulting anti-science movement puts the research community, scientific research, and pandemic preparedness at risk., Competing Interests: T.D. is on the Board of Directors, Burroughs Wellcome Fund, and is an Editor for the Annual Review of Virology. P.D. receives funding from Moderna. K.F. has substantial financial interest in Vir Biotechnology, Inc., and is cofounder of the company and is coinventor of patents licensed to Vir and receives compensation for consulting. The potential conflict of interest has been reviewed and managed by OHSU. S.G. has done legal consulting on the origins of the pandemic. A.L.G. reports central testing contracts from Pfizer, Novavx, Sanofi, Abbott, Hologic, Cephid, and Quidel and has research support from Gilead. A.M. is scientific founder of Thylacine Biotherapeutics. G.A.S. is President of Thyreos, Inc. Most authors receive funding from the National Institutes of Health and other funding agencies.

Folate-dependent one-carbon (C1) metabolism encompasses distinct cytosolic and mitochondrial pathways connected by an interchange among serine, glycine, and formate. In both the cytosol and mitochondria, folates exist as polyglutamates, with polyglutamylation catalyzed by folylpolyglutamate synthetase (FPGS), including cytosolic and mitochondrial isoforms. Serine is metabolized by serine hydroxymethyltransferase (SHMT)2 in the mitochondria and generates glycine and C1 units for cellular biosynthesis in the cytosol. AGF347 is a novel pyrrolo[3, 2-day ]pyrimidine antifolate that targets SHMT2 in the mitochondria and SHMT1 and de novo purine biosynthesis in the cytosol. FPGS is expressed in primary pancreatic cancer specimens, and FPGS levels correlate with in vitro efficacies of AGF347 toward human pancreatic cancer cells. MIA PaCa-2 pancreatic cancer cells with CRISPR knockout of FPGS were engineered to express doxycycline-inducible FPGS exclusively in the cytosol (cFPGS) or in both the cytosol and mitochondria (mFPGS). Folate and AGF347 accumulations increased in both the cytosol and mitochondria with increased mFPGS but were restricted to the cytosol with cFPGS. AGF347-Glu 5 inhibited SHMT2 ∼19-fold greater than AGF347 By metabolomics analysis, mFPGS stimulated the C1 flux from serine in the mitochondria and de novo purine and dTTP synthesis far greater than cFPGS. mFPGS enhanced in vitro inhibition of MIA PaCa-2 cell proliferation by AGF347 (∼30-fold) more than cFPGS (∼4.9-fold). Similar results were seen with other pyrrolo[3, 2-d ]pyrimidine antifolates ( AGF291, AGF320 ); however, elevated mFPGS adversely impacted inhibition by the nonclassical SHMT2/SHMT1 inhibitor SHIN1. These results suggest a critical role of mFPGS levels in determining antitumor efficacies of mitochondrial-targeted pyrrolo[3, 2-d ]pyrimidine antifolates for pancreatic cancer. SIGNIFICANCE STATEMENT: AGF347 is a novel pyrrolo[3, 2-d ]pyrimidine antifolate that targets serine hydroxymethyltransferase (SHMT)2 in the mitochondria and SHMT1 and de novo purine biosynthesis in the cytosol. AGF347 accumulation increases with folylpolyglutamate synthetase (FPGS) levels in both the cytosol and mitochondria. Increased mitochondrial FPGS stimulated one-carbon metabolic fluxes in the cytosol and mitochondria and substantially enhanced in vitro inhibition of pancreatic cancer cells by AGF347 . Mitochondrial FPGS levels play important roles in determining the antitumor efficacies of pyrrolo[3, 2-d ]pyrimidine antifolates for pancreatic cancer., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Objective: The ways that mental health concepts are represented on social media could have significant implications for lay understandings and behavior. The current article reports an analysis of how trauma is represented on TikTok, one of the world's most popular social media platforms., Method: Following a search for content using the hashtag #trauma, 143 videos were subjected to qualitative content analysis to characterize the profiles of their producers, intended function, and trauma-related content., Results: Results show that most videos were produced by young White people, who drew on their personal experience of trauma to generate confessional narratives or raise awareness of trauma. Trauma was most often attributed to childhood adversity or relationship difficulties. A diverse range of behaviors and experiences were positioned as evidence of trauma., Conclusions: Findings are consistent with prior suggestions that trauma's boundaries are expanding in the form of "concept creep," but also draw attention to the role of humor and irony in social media invocations of the concept. Given the current near-ubiquity of social media consumption, particularly among young people, establishing the implications of exposure to this content should be a priority for future research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The burden of treatment (BOT) related to propranolol treatment for infantile hemangiomas (IH) has never previously been explored. A modified validated questionnaire, the Treatment Burden Questionnaire, and one-on-one semi-structured interviews were used to assess the BOT for propranolol for IH. Out of 80 caregivers, the overall burden score was very low at 1.2 out of 10; thematic analysis of interviews grouped themes into administration, monitoring, financial, and associated anomalies. The BOT of propranolol for IH is very low but could be reduced further by offering age-based risk stratification related to feeding frequency and risk of hypoglycemia, pragmatic advice around timing of doses before sleep, and reducing frequency of vital sign monitoring., (© 2024 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Objective: To identify whether conventional methods of estimating fetal growth (Hadlock's formula), which relies heavily on abdominal circumference measurements, are accurate in fetuses with gastroschisis., Methods: A retrospective cohort study was performed between the period January 1, 2011 and December 31, 2021 in a tertiary referral maternity hospital identifying all pregnancies with a diagnosis of gastroschisis. Projected fetal weight was obtained using the formula (EFW [Hadlock's formula] + 185 g × [X/7]) where X was the number of days to delivery., Results: During the study period 41 cases were identified. The median maternal age was 25. The median BMI was 25 and 63% were primiparous women (n = 26). Median gestation at diagnosis was 21 weeks. Median gestation at delivery was 36 weeks. A total of 4.8% of mothers had a history of drug use (n = 2). The rate of maternal tobacco use was 21.9% (n = 9). A total of 4.8% of fetuses had additional congenital anomalies including amniotic band syndrome and myelomeningocele (n = 2). Estimated fetal weight (EFW) and birth weight data were available for 34 cases. A Wilcoxon signed-rank test showed projected EFW using Hadlock's formula did not result in a statistically significant different birth weight (Z = -1.3, P = 0.169). Median projected weight and actual birth weight were 2241.35 and 2415 g respectively. Median difference was 0.64 g (95% CI: -148 to -28.5)., Conclusion: Our data showed accuracy using standard formulae for EFW in fetuses with gastroschisis., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Several ablation confirmation software methods for minimum ablative margin assessment have recently been developed to improve local outcomes for patients undergoing thermal ablation of colorectal liver metastases. Previous assessments were limited to single institutions mostly at the place of development. The aim of this study was to validate the previously identified 5 mm minimum ablative margin (A0) using autosegmentation and biomechanical deformable image registration in a multi-institutional setting., Methods: This was a multicentre, retrospective study including patients with colorectal liver metastases undergoing CT- or ultrasound-guided microwave or radiofrequency ablation during 2009-2022, reporting 3-year local disease progression (residual unablated tumour or local tumour progression) rates by minimum ablative margin across all institutions and identifying an intraprocedural contrast-enhanced CT-based minimum ablative margin associated with a 3-year local disease progression rate of less than 1%., Results: A total of 400 ablated colorectal liver metastases (median diameter of 1.5 cm) in 243 patients (145 men; median age of 62 [interquartile range 54-70] years) were evaluated, with a median follow-up of 26 (interquartile range 17-40) months. A total of 119 (48.9%) patients with 186 (46.5%) colorectal liver metastases were from international institutions B, C, and D that were not involved in the software development. Three-year local disease progression rates for 0 mm, >0 and <5 mm, and 5 mm or larger minimum ablative margins were 79%, 15%, and 0% respectively for institution A (where the software was developed) and 34%, 19%, and 2% respectively for institutions B, C, and D combined. Local disease progression risk decreased to less than 1% with an intraprocedurally confirmed minimum ablative margin greater than 4.6 mm., Conclusion: A minimum ablative margin of 5 mm or larger demonstrates optimal local oncological outcomes. It is proposed that an intraprocedural minimum ablative margin of 5 mm or larger, confirmed using biomechanical deformable image registration, serves as the A0 for colorectal liver metastasis thermal ablation., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: One-way text messaging to re-engage people in HIV care has shown promise, but little is known about two-way messaging where the recipient is asked to respond. We evaluated a two-way text messaging intervention, informed by behavioural science, to increase re-engagement in care following missed antiretroviral therapy (ART) visits., Methods: We conducted an individual-level randomised controlled trial between February and March 2023 in Capricorn District, South Africa. Adults aged ≥18 years who had missed an ART visit by >28 days were randomised to (1) a standard one-way text message, or (2) behaviourally informed two-way text messages. Two-way messages asked recipients to reply by selecting from a list of reasons for their missed visit. Those who responded received another text message tailored to their response and designed using behavioural economics principles (affect heuristic, availability heuristic, loss aversion, social norms, providing slack, expanding choice). The primary outcome was return to care within 45 days, analysed as 1) intention to treat, and 2) restricted to successful message delivery., Results: 3,695 participants were randomised: 1,845 to the one-way message group and 1,850 to the two-way message group. 27.9% (515/1845) of participants sent a one-way message and 27.2% (503/1850) sent a two-way message returned for an ART visit within 45 days (proportion difference:-0.7%, p-value: 0.622). In an analysis restricted to participants whose text message was delivered, 28.3% (310/1094) in the one-way message group compared to 28.3% (304/1076) in the two-way message group returned to care (proportion difference:-0.09%, p-value: 0.966). 19.5% (210/1076) responded to the two-way message. The two most commonly reported reasons for missed appointments were being out of town (41.0%) and still having medication (31.0%.). Among those who responded, 27.1% (95%CI: 21.3-33.7) returned for an ART visit. Clients ≥50 years were less likely to respond to the two-way text message, (AOR 0.4; 95%CI: 0.2-0.9)., Conclusions: Behaviourally informed two-way text messages did not improve return to care over one-way messages. However, they elicited reasons for disengagement, which could inform future outreach for missed visits. Additional research is needed on the mode, content and timing of two-way messages intended to increase return to care., Clinical Trial Number: PACTR202202748760768 & DOH-27-042022-6703.

The KidGen Collaborative's Policy Implementation Workshop 2023 celebrated the 10th anniversary of Australia's first kidney genetics clinic in Brisbane. This event marked the establishment of a national network now comprising 19 kidney genetics clinics across Australia, all dedicated to providing equitable access to genomic testing for families affected by genetic kidney diseases. The workshop reflected on past progress and outlined future objectives for kidney genetics in Australia, recognising the collaborative efforts of clinical teams, researchers, and patients. Key insights from the workshop are documented in the proceedings., (© 2024. The Author(s).)

The inevitable attrition of skin due to ultraviolet radiation, termed photoaging, can be partially restored by treatment with retinoid compounds. Photoaged skin in lightly pigmented individuals, clinically presents with the appearance of wrinkles, increased laxity, and hyper- and hypopigmentation. Underlying these visible signs of ageing are histological features such as epidermal thinning, dermal-epidermal junction flattening, solar elastosis and loss of the dermal fibrillin microfibrillar network, fibrillar collagen and glycosaminoglycans. Retinoid compounds are comprised of three main generations with the first generation (all-trans retinoic acid, retinol, retinaldehyde and retinyl esters) primarily used for the clinical and cosmetic treatment of photoaging, with varying degrees of efficacy, tolerance and stability. All-trans retinoic acid is considered the 'gold standard' for skin rejuvenation; however, it is a prescription-only product largely confined to clinical use. Therefore, retinoid derivatives are readily incorporated into cosmeceutical formulations. The literature reported in this review suggests that retinol, retinyl esters and retinaldehyde that are used in many cosmeceutical products, are efficacious, safe and well-tolerated. Once in the skin, retinoids utilize a complex signalling pathway that promotes remodelling of photoaged epidermis and dermis and leads to the improvement of the cutaneous signs of photoaging., (© 2024 The Author(s). International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation and transcriptome sequencing (snmCT-seq) in frontal cortex from young adult and aged donors, we found widespread age- and sex-related variation in specific neuron types. The proportion of inhibitory SST- and VIP-expressing neurons was reduced in aged donors. Excitatory neurons had more profound age-related changes in their gene expression and DNA methylation than inhibitory cells. Hundreds of genes involved in synaptic activity, including EGR1, were less expressed in aged adults. Genes located in subtelomeric regions increased their expression with age and correlated with reduced telomere length. We further mapped cell-type-specific sex differences in gene expression and X-inactivation escape genes. Multi-omic single-nucleus epigenomes and transcriptomes provide new insight into the effects of age and sex on human neurons., Competing Interests: Declaration of interests J.R.E. serves on the scientific advisory board of Zymo Research Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The 'gold standard' for the treatment of photoaged white skin is all-trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin-rich microfibrils (FRMs) at the dermal-epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated., Objectives: To determine the potential of retinoids to repair photoaged black skin., Methods: An exploratory intervention study was performed using an in vivo, short-term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4-day application due to irritancy) or ROL (12-day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid-treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling., Results: Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control., Conclusions: This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR-induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Men who have sex with men (MSM) are disproportionately affected by HIV. Given that over 70% of MSM meet sexual partners via dating apps, such apps may be an effective platform for promoting HIV pre-exposure prophylaxis (PrEP) use. We aimed to describe preferences among MSM for PrEP advertisements displayed on dating apps. We conducted individual in-depth interviews with 16 MSM recruited from a mobile sexual health unit in Boston, Massachusetts. Two focus groups were also held: one with mobile unit staff ( N  = 3) and one with mobile unit users ( N  = 3). Content analysis was used to identify themes related to advertisement content and integration with app use. Mean participant age was 28 (SD 6.8); 37% identified as White and 63% as Latinx. 21% of interviews were conducted in Spanish. Preferences were organized around four themes: (1) relevant and relatable advertisements, (2) expansion of target audiences to promote access, (3) concise and captivating advertisements, and (4) PrEP advertisements and services as options, not obligations. MSM are supportive of receiving information about PrEP on dating apps, but feel that existing advertisements require modification to better engage viewers. Dating apps may be an underutilized tool for increasing PrEP awareness and knowledge among MSM.

Recent changes in climate and human land-use have resulted in alterations of the geographic range of many species, including human pathogens. Geographic range expansion and population growth of human pathogens increase human disease risk. Relatively little empirical work has investigated the impact of range changes on within-population variability, a contributor to both colonization success and adaptive potential, during the precise time in which populations are colonized. This is likely due to the difficulties of collecting appropriate natural samples during the dynamic phase of migration and colonization. We systematically collected blacklegged ticks (Ixodes scapularis) across New York State (NY), USA, between 2006 and 2019, a time period coinciding with a rapid range expansion of ticks and their associated pathogens including Borrelia burgdorferi, the etiological agent of Lyme disease. These samples provide a unique opportunity to investigate the population dynamics of human pathogens as they expand into novel territory. We observed that founder effects were short-lived, as gene flow from long-established populations brought almost all B. burgdorferi lineages to newly colonized populations within just a few years of colonization. By 7 years post-colonization, B. burgdorferi lineage frequency distributions were indistinguishable from long-established sites, indicating that local B. burgdorferi populations experience similar selective pressures despite geographic separation. The B. burgdorferi lineage dynamics elucidate the processes underlying the range expansion and demonstrate that migration into, and selection within, newly colonized sites operate on different time scales., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

Clinical trials are vital for assessing therapeutic interventions. The associated data monitoring committees (DMCs) safeguard patient interests and enhance trial integrity, thus promoting timely, reliable evaluations of those interventions. We face an urgent need to recruit and train new DMC members. The HFC (Heart Failure Collaboratory), a multidisciplinary public-private consortium of academics, trialists, patients, industry representatives, and government agencies, is working to improve the clinical trial ecosystem. The HFC aims to improve clinical trial efficiency and quality by standardizing concepts, and to help meet the demand for experienced individuals on DMCs by creating a standardized approach to training new members. This paper discusses the HFC's training workshop, and an apprenticeship model for new DMC members. It describes opportunities and challenges DMCs face, along with common myths and best practices learned through previous experiences, with an emphasis on data confidentiality and need for quality independent statistical reporting groups., Competing Interests: Funding Support and Author Disclosures Dr Fleming has received consulting fees from the National Institutes of Health, the World Health Organization, the Food and Drug Administration, and the pharmaceutical and biotech industry in the design, monitoring, and analysis of clinical trials; and he has received fees for serving on several industry-sponsored Data Monitoring Committees (DMCs). Dr Wittes has received compensation for her membership on several DMCs sponsored by industry, government, and not-for-profit organizations; and has received consulting fees from a variety of pharmaceutical and medical device companies. Dr Bristow is the President/CEO/Director at ARCA biopharma. Dr Rockhold has received consulting fees from Intercept, Clover, and Inventprise; has received compensation for serving on several industry-sponsored DMCs; and holds stock in Clover, GSK, Athira, Spence, Adaptic, and Doctor Evidence. Dr Claggett has received consulting fees from Alnylam, Axon, Cardior, Cardurion, CVRx, Cytokinetics, Intellia, and Rocket. Dr Abraham has received consulting fees from Boehringer Ingelheim, Cardionomic, Zoll Respicardia, scPharmaceuticals, Sensible Medical, and Vectorious; has received salary support from V-Wave Medical; and has served as a speaker for Edwards Lifesciences. Dr Lindenfeld has received consulting fees from Abbott, ADI, Alleviant, Amgen, AstraZeneca, Axon, Boston Scientific, Cordio, CVRx, Cytokinetics, Edwards Lifesciences, Medtronic, Merck, VWave, Vascular Dynamics, Vectorious, and Whiteswell; and has received grants from Analog Devices Inc, AstraZeneca, and Volumetrix. Dr DeMets has received consulting fees from the National Institutes of Health, the U.S. Food and Drug Administration, and the pharmaceutical and medical device industry on the design, monitoring, and analysis of clinical trials; and he has received compensation for serving on several recent industry-sponsored data and safety monitoring committees or steering committees including AstraZeneca, Bristol Meyers Squib, GSK, Merck, Boston Scientific, Medtronic, USONA, LivaNova, AnthosTherapy, ARCA biopharma, Duke Clinical Research Institute, and the Population Health Research Institute of Hamilton Ontario. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic pain and mental health issues occur at higher rates in Veterans than the general population. One widely recognized mental health issue faced by Veterans is post-traumatic stress disorder (PTSD). Trauma symptoms and pain frequently co-occur and are mutually maintained due to shared mechanisms. Many Veterans are also parents. Parental physical and mental health issues significantly predict children's chronic pain and related functioning, which can continue into adulthood. Only 1 U.S.-based study has examined pain in the offspring of Veterans, suggesting a heightened risk for pain. Research to date has not examined the associations between trauma and pain and the dyadic influences of these symptoms, among Veterans, and their children. The current study aimed to describe pain characteristics in Canadian Armed Forces Members/Veterans with chronic pain and their offspring (youth and adult children aged 9-38). Cross-lagged panel models were conducted to examine dyadic relationships between pain interference and trauma symptoms of Canadian Armed Forces Members/Veterans and their offspring. Over half of adult offspring and over one-quarter of youth offspring reported chronic pain. Results revealed effects between one's own symptoms of PTSD and pain interference. No significant effects of parents on offspring or offspring on parents were found. The findings highlight the interconnection between pain and PTSD consistent with mutual maintenance models and a lack of significant interpersonal findings suggestive of resiliency in this unique population. PERSPECTIVE: We characterized chronic pain in the offspring of Canadian Armed Forces Members/Veterans with chronic pain and examined dyadic relationships between PTSD symptoms and chronic pain interference. Findings revealed that PTSD symptoms and pain interference were related within Veterans and offspring, but no dyadic relationships were found, which could reflect resiliency., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Treatment interruptions are a barrier to successful antiretroviral therapy (ART). 'Fresh start messages', which leverage significant days on the calendar (e.g., new year, public holiday) in order to prompt action, have the potential to encourage people with HIV (PWH) to return to care. We evaluated a 'fresh start' intervention (text messages) to increase return to care in PWH who had missed their last appointment., Design: A three arm 1 : 1:1 individual randomised controlled trial., Methods: We randomized adults in Capricorn District who had missed ART appointments by >28 days to: no text message; unframed messages (fresh start not mentioned); or framed messages (fresh start mentioned). Randomization was stratified by treatment interruption duration and across two holidays (Youth Day, Mandela Day). The primary outcome was an ART-related clinic visit at ≤45 days of the first message., Results: 9143 participants were randomised. For Youth Day, 1474 and 1468 were sent unframed and framed messages respectively, with 13.4% sent these messages having an ART visit vs. 11.9% not sent a message [adjusted odds ratio (aOR) 1.2; 95% confidence interval (CI): 1.0-1.4, P -value = 0.075]. For Mandela Day, 1336 and 1334 were sent unframed and framed messages respectively, with 6.7% sent these messages having an ART-related clinic visit vs. 5.4% not sent a message (aOR 1.2; 95% CI: 1.0-1.6; P -value = 0.100)., Conclusions: Low-cost text messages sent around a 'fresh start' date may increase the likelihood that patients who miss appointments return to care. This study suggests the potential of text messaging for motivating return to care., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: HIV testing rates among South African men lag behind rates for women and national targets. Community-based HIV self-screening (HIVSS) distribution and follow-up by community health workers (CHWs) is a scalable option to increase testing coverage, diagnosis, and treatment initiation. We provided HIVSS and assisted linkage to care to men not recently tested (within the past 12 months) residing in high-HIV-burden areas of Johannesburg., Methods: CHWs distributed HIVSS in 6 clinic catchment areas. Follow-up to encourage confirmatory testing and antiretroviral therapy initiation was conducted through personal support (PS) or an automated short message service (SMS) follow-up and linkage system in 3 clinic areas each. Using a quasi-experimental pre-post design, we compared differences in the proportion of men testing in the clinic catchment areas during the HIVSS campaign (June-August 2019) to the 3 months prior (March-May 2019) and compared treatment initiations by assisted linkage strategy., Results: Among 4793 participants accepting HIVSS, 62% had never tested. Among 3993 participants with follow-up data, 90.6% reported using their HIVSS kit. Testing coverage among men increased by 156%, from under 4% when only clinic-based HIV testing services were available to 9.5% when HIVSS and HIV testing services were available (z = -11.6; P < 0.01). Reported test use was higher for men followed through PS (99% vs. 68% in SMS); however, significantly more men reported reactive self-test results in the SMS group compared with PS (6.4% vs. 2.0%), resulting in more antiretroviral therapy initiations in the SMS group compared with PS (23 vs. 9; P < 0.01)., Conclusions: CHW HIVSS distribution significantly increases testing among men. While PS enabled personalized follow-up, reporting differences indicate SMS is more acceptable and better aligned with expectations of privacy associated with HIVSS., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To standardize international normalized ratio (INR) measurements and improve data integrity by enabling electronic result transmission for warfarin monitoring, two point-of-care (POC) devices were evaluated against an internal plasma INR reference method., Methods: A multicenter study was pursued (January 24, 2022, through October 19, 2022) to compare concordance of two commercially available POC devices, Coag-Sense PT2 Meter (Coag-Sense) and CoaguChek XS Pro and Plus devices (CoaguChek), against an internal plasma INR method among patients treated with warfarin. Bias and linear regression analysis were assessed for these devices including dosing decision accuracy compared with plasma INR reference., Results: Two hundred ninety-nine patients treated with warfarin across three Mayo Clinic sites agreed to participate. Atrial fibrillation (n=191, 63.9%), venous thromboembolism (n=65; 21.7%), and heart valve prosthesis (n=46; 15.4%) were common anticoagulant indications with a 2.5 INR target for 280 (93.6%) of patients. For the CoaguChek devices, 243 (81.3%) of values fell within 0.2 INR units with plasma INR referent and 285 (95.3%) within 0.4 units (R 2 =0.93). For the Coag-Sense device, 102 (34.1%) of values fell within 0.2 INR units and 180 (60.2%) within 0.4 INR units of plasma INR values, (R 2 =0.83; P<.0001). Using the plasma INR as the gold standard, appropriate dosing recommendations would have occurred for 292 (97.7%) of the CoaguChek and 244 (81.6%) of the Coag-Sense results., Conclusion: Compared with a plasma referent, INR values obtained from the CoaguChek devices exhibited less systematic bias compared with Coag-Sense measures. This translates to a greater percentage of concordant management decisions between POC and laboratory INR methods., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Cardiovascular disease, associated risk factors and obesity are prevalent after liver transplant and modifiable through lifestyle changes. Understanding what lifestyle interventions and their respective components are effective is essential for translation to clinical practice. We aimed to investigate the effects of diet and physical activity interventions on weight, body mass index and other cardiovascular disease risk factors in liver transplant recipients, and systematically describe the interventions., Methods: We systematically searched Embase, MEDLINE, Psycho Info, CINAHL, Cochrane central register of controlled trials, PeDro, AMED, BNI, Web of Science, OpenGrey, ClinicalTrials.gov and the international clinical trials registry from inception to 31 May 2023. Search results were screened by two independent reviewers: randomised control trials with interventions that targeted diet and physical activity behaviours in liver transplant recipients were considered eligible. Two independent reviewers extracted and synthesised data for study, participant and intervention details and results. We used the Revised Cochrane Risk of Bias Tool for Randomised Trials to assess risk of bias for outcomes and the GRADE approach to rate the quality of the body of evidence. When two or more studies reported findings for an outcome, we pooled data using random-effects meta-analysis., Results: Six studies were included, reporting three physical activity and three combined diet and physical activity interventions. Participants were 2 months-4 years post-transplant. Interventions lasted 12 weeks-10 months and were delivered remotely and/or in-person, most commonly delivered to individual participants by health care or sports professionals. Five studies described individual tailoring, e.g. exercise intensity. Adherence to interventions ranged from 51% to 94%. No studies reported fidelity. Intervention components were not consistently reported. In meta-analysis, diet and physical activity interventions did not significantly reduce weight or body mass index compared to control groups, however no studies targeted participants with obesity. Diet and physical activity interventions reduced percentage body fat and triglycerides compared to control groups but did not reduce total cholesterol or increase activity. The GRADE quality of evidence was low or very low., Conclusion: Diet and physical activity interventions reduced percentage body fat and triglycerides in liver transplant recipients. Further good quality research is needed to evaluate their effect on other cardiovascular disease risk factors, including weight and BMI. Interventions need to be better described and evaluated to improve evidence base and inform patient care., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: There is limited understanding of the hypothesized association between the Ehlers-Danlos Syndromes (EDS), hypermobility and fractures in children. Despite this, EDS and hypermobility continue to be raised in the legal setting as possible causes of unexplained fractures in infants where there is a concern for physical abuse. Further understanding is needed regarding fractures in children with EDS and hypermobility., Objective: This study assessed fracture prevalence and characteristics in children diagnosed with EDS and Generalized Joint Hypermobility (GJH). The secondary outcome was fracture prevalence in infants <1 year of age., Participants and Setting: Children aged <18 years with EDS or GJH seen in a single-center EDS clinic from April 2017 to December 2021 were included. Diagnoses were based on the 2017 international classification. Exclusion criteria were concurrent medical conditions associated with bone fragility., Methods: This retrospective descriptive study examined variables including fracture history, fracture location, fracture type, age of sustaining fracture, and injury mechanism. Descriptive statistics were used for analysis., Results: Fracture prevalence was 34.6 % (9/26, 95 % CI [16.3, 52.9]) in the EDS population and 25.4 % (15/59, 95 % CI [14.3, 36.5]) in the GJH population. No fractures occurred in infancy. Most fractures occurred in the limbs. There were no rib or skull fractures. Most fractures were the result of an identifiable injury event., Conclusion: In a cohort of children with formally diagnosed EDS or GJH, fractures occurred commonly in ambulatory children and generally in the limbs from identifiable events. This study does not support EDS or GJH as a cause of fractures in infancy., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

KLRG1 + CD8 T cells persist for months after clearance of acute infections and maintain high levels of effector molecules, contributing protective immunity against systemic pathogens. Upon secondary infection, these long-lived effector cells (LLECs) are incapable of forming other circulating KLRG1 - memory subsets such as central and effector memory T cells. Thus, KLRG1 + memory T cells are frequently referred to as a terminally differentiated population that is relatively short lived. Here, we show that after viral infection of mice, effector cells derived from LLECs rapidly enter nonlymphoid tissues and reduce pathogen burden but are largely dependent on receiving antigen cues from vascular endothelial cells. Single-cell RNA sequencing reveals that secondary memory cells in nonlymphoid tissues arising from either KLRG1 + or KLRG1 - memory precursors develop a similar resident memory transcriptional signature. Thus, although LLECs cannot differentiate into other circulating memory populations, they still retain the flexibility to enter tissues and establish residency.

Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes. GBM arises in the specialized brain immune environment dominated by microglia, so we explored sex differences in this immune cell type. We isolated adult human TAM-MGs (tumor-associated macrophages enriched for microglia) and control microglia and found sex-biased inflammatory signatures in GBM and lower-grade tumors associated with pro-tumorigenic activity in males and anti-tumorigenic activity in females. We demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this bias. Together, our results implicate TAM-MGs, specifically their sex chromosomes, as drivers of male bias in GBM., Competing Interests: Declaration of interests The authors declare no competing interests.