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Introduction : The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods : A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results : A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus , Streptococcus species, Enterococcus faecalis , Kingella kingae , Neisseria gonorrhoeae , and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion : The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting., Competing Interests: At least one of the (co-)authors is a member of the editorial board of Journal of Bone and Joint Infection. The peer-review process was guided by an independent editor, and the authors also have no other competing interests to declare., (Copyright: © 2024 Stéphanie Pascual et al.)

Circularly polarized light (CPL) is a versatile tool to prepare chiral nanostructures, but the mechanism for inducing enantioselectivity is not well understood. This work shows that the energy and polarization of visible photons can initiate photodeposition at different sites on plasmonic nanocrystals. Here, CPL on achiral gold bipyramids (AuBPs) creates hot holes that oxidatively deposit PbO 2 asymmetrically. We show for the first time that the location of PbO 2 photodeposition and hence optical dissymmetry depends on the CPL wavelength. Specifically, 488 and 532 nm CPL induce PbO 2 growth in the middle of AuBPs, whereas 660 nm CPL induces PbO 2 growth at the tips. Our observations show that wavelength-dependent plasmonic field distributions are more important than surface lightning rod effects in localizing plasmon-mediated photochemistry. The largest optical dissymmetry occurs at excitation wavelengths between the transverse and longitudinal resonances of the AuBPs because higher-order modes are required to induce chiral electric fields.

This mixed method study developed multiple question types to understand and measure women's perceived benefit from adjuvant endocrine therapy. We hypothesis that patients do not understand this benefit and sought to develop the questions needed to test this hypothesis and obtain initial patient estimates. From 8/2022 to 3/2023, qualitative interviews focused on assessing and modifying 9 initial varied question types asking about the overall survival (OS) benefit from adjuvant endocrine therapy. Subsequent focus groups modified and selected the optimal questions. Patients' self-assessment of their OS benefit was compared to their individualized PREDICT model results. Fifty-three patients completed the survey; 42% Hispanic, 30% rural, and 47% with income < $39,999 per year. Patients reported adequate health care literacy (61.5%) and average confidence about treatment and medication decisions 49.4 (95% CI 24.4-59.5). From the original 9 questions, 3 modified questions were ultimately found to capture patients' perception of this OS benefit, focusing on graphical and prose styles. Patients estimated an OS benefit of 42% compared to 4.4% calculated from the PREDICT model (p < 0.001). In this group with considerable representation from ethnic minority, rural and low-income patients, qualitative data showed that more than one modality of question type was needed to clearly capture patients' understanding of treatment benefit. Women with breast cancer significantly overestimated their 10-year OS benefit from adjuvant endocrine therapy compared to the PREDICT model., (© 2024. The Author(s).)

In October 2023, the Food and Drug Administration (FDA) released a proposed rule that ends enforcement discretion for laboratory-developed tests (LDTs). The FDA's proposal outlines a five-stage implementation to begin regulating LDTs as they do for commercial in vitro diagnostics (IVDs), including modified FDA-approved/cleared tests. We outline here concerns from the clinical and public health microbiology laboratory perspective. It is our opinion that LDTs performed by individual Clinical Laboratory Improvement Amendments-certified diagnostic laboratories should not be regulated in the same way as commercial IVDs. This rule, if finalized, will negatively impact the diagnostic services currently offered by clinical and public health laboratories and, therefore, patients and the providers who care for them. Ending enforcement discretion will likely stifle diagnostic innovation and decrease access to diagnostic testing and health equity. Furthermore, the lack of infrastructure, including personnel and funding, at the FDA and diagnostic laboratories to support the required submissions for review is an obstacle. Like the FDA, diagnostic laboratories prioritize patient safety, accurate clinical diagnostics, and health equity. Since the scope of the LDT landscape is currently unknown, we are supportive of a registration process, along with non-burdensome adverse event reporting, to first understand the scope of clinical use of LDTs and any associated safety concerns. Any regulatory rule should be based on data that have been gathered systematically, not anecdotes or case reports. A rule must also balance the potential negative impact to patient care with realistic safety risks for infectious disease diagnostics., Competing Interests: The authors declare no conflict of interest.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is considered a safe and promising tool for limb rehabilitation after stroke, but its effect on cough has never been studied. It is known that the ear and larynx share vagal afferent pathways, suggesting that stimulating the ear with taVNS might have effects on cough sensitivity. The specific stimulation parameters used can influence outcomes., Objective: To investigate the effect of various stimulation parameters on change in cough sensitivity, compared to the reference parameter of 25 Hz stimulation at the left concha (most commonly-used parameter for stroke rehabilitation). Design, setting, and participants: Randomized, single-blind, active-controlled, eight-period cross-over design conducted March to August 2022 at a New Zealand research laboratory with 16 healthy participants., Interventions: All participants underwent eight stimulation conditions which varied by stimulation side (right ear, left ear), zone (ear canal, concha), and frequency (25 Hz, 80 Hz). Main outcome measures: Change in natural and suppressed cough threshold (from baseline to after 10 min of stimulation) assessed using a citric acid cough reflex test., Results: When compared to the reference parameter of 25 Hz stimulation at the left concha, there was a reduction in natural cough threshold of -0.16 mol/L for 80 Hz stimulation at the left canal ( p  = 0.004), indicating increased sensitivity. For the outcome measure of suppressed cough threshold, there was no significant effect of any of the stimulation conditions compared to the active reference., Conclusion: Since stroke patients often have cough hyposensitivity with resulting high risk of silent aspiration, using 80 Hz taVNS at the left canal may be a better choice for future stroke rehabilitation studies than the commonly used 25 Hz taVNS at the left concha. Treatment parameters should be manipulated in future sham-controlled trials to maximize any potential treatment effect of taVNS in modulating cough sensitivity., Clinical Trial Registration: ACTRN12623000128695., Competing Interests: YC has numerous patents on wearables, including auricular stimulators and he is a shareholder at Stoparkinson LLC. The remaining 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ng, Guiu Hernandez, Haszard, Macrae, Huckabee and Cakmak.)

The LYMQOL Leg questionnaire is the most widely used, evidence-based tool for the assessment of health-related quality of life (HRQoL) in patients with lower limb lymphedema (LLL). It has been translated into several languages, but a German version is currently lacking. The aim of our study was to validate a German translation of LYMQOL Leg. Translation and cross-cultural adaptation were performed in accordance with ISPOR principles. A total of 103 patients with LLL from Germany, Austria, and Switzerland were interviewed twice. The content and face validity assessments indicated that the German LYMQOL Leg questionnaire was acceptable for interviewing patients with lymphedema. Comparing the LYMQOL Leg with the SF-36 demonstrated good construct validity. Reliability determined by the test-retest procedure was good (intra-class-correlation coefficients 0.68-0.92). Cronbach's alpha values ranged from 0.76 to 0.90 in both interviews, showing an acceptable internal consistency. The four domains of the questionnaire reached a cumulative variance of 52.7% in the factor analysis. The association between the lymphedema stages and the LYMQOL Leg domain scores was not significant. In conclusion, the validity of the German version of LYMQOL Leg, called LYMQOL Bein , was confirmed and thus represents a suitable tool for measuring HRQoL in German-speaking patients with LLL.

The nutritional quality of a colony significantly affects its health and strength, particularly because it is required for population growth in the early spring. We investigated the impact of various artificial pollen substitute diets on colony performance in the Republic of Korea during early spring, a critical period for colony health and growth. The colonies were provided with different diets, including the commercial product Megabee (positive control), our developed diet Test A, and four upgraded versions (Diet 1, Diet 2, Diet 3, and Diet 4) of Test A. The negative control group received no supplementary feed. Over 63 days, we observed 24 experimental colonies and assessed various parameters at the colony and individual levels. The results revealed that Diet 2 had the highest consumption and had the most positive impact on population growth, the capped brood area, colony weight, honey bees' weight, and vitellogenin levels. These findings suggested that Diet 2 is most attractive to honey bees and thus holds great promise for improving colony maintenance and development during the crucial early spring period.

Background: Local application site reactions are common with sublingual allergy immunotherapy (AIT)-tablets for the treatment of allergic rhinitis/conjunctivitis (AR/C) and occasionally lead to treatment discontinuation. Because of the lower mast cell density in the vestibular mucosa than the sublingual area, vestibular AIT-tablet administration may result in fewer adverse events (AEs). This pilot study evaluated the tolerability of the vestibular administration route of AIT-tablets compared with the sublingual route in adult subjects with AR/C., Methods: Adults (n = 164) aged 18-65 years with AR/C treated with daily birch pollen, grass pollen, ragweed pollen or house dust mite AIT in tablet form were randomized 1:1 to vestibular or sublingual administration for 28 days, followed by 28 days of sublingual administration only. The primary endpoint was the severity (mild, moderate, severe) of local treatment-related adverse events (TRAEs) during the first 28 days of treatment., Results: During the first 28 days, the percentage of subjects in the vestibular and sublingual groups reporting mild TRAEs were 55.6% versus 50.6%, respectively; moderate TRAEs were 27.2% versus 30.1%; and severe TRAEs were 12.3% versus 6.0% (p = .16). In the vestibular group, 95.1% of the subjects experienced at least one TRAE during the first period versus 81.9% in the sublingual group (p = .01) and discontinuation rates due to AEs were higher (12.3% vs. 3.6%)., Conclusion: The frequencies of subjects experiencing severe TRAEs, at least one TRAE, and discontinuations due to AEs at the initiation of AIT-tablets were numerically higher with vestibular administration than sublingual administration. Sublingual administration should remain the standard of care for subjects treated with AIT-tablets for AR/C., (© 2023 John Wiley & Sons Ltd.)

Introduction: Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance and memory decline., Methods: We conducted a cross-ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts., Results: We found high heritability for two ancestry backgrounds. Further, we found a novel ancestry locus for memory decline on chromosome 4 (rs6848524) and three loci in the non-Hispanic Black ancestry group for memory performance on chromosomes 2 (rs111471504), 7 (rs4142249), and 15 (rs74381744). In our gene-level analysis, we found novel genes for memory decline on chromosomes 1 (SLC25A44), 11 (BSX), and 15 (DPP8). Memory performance and memory decline shared genetic architecture with AD-related traits, neuropsychiatric traits, and autoimmune traits., Discussion: We discovered several novel loci, genes, and genetic correlations associated with late-life memory performance and decline., Highlights: Late-life memory has high heritability that is similar across ancestries. We discovered four novel variants associated with late-life memory. We identified four novel genes associated with late-life memory. Late-life memory shares genetic architecture with psychiatric/autoimmune traits., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, except atg-16.2, increased lifespan, and decreased neuronal PolyQ aggregates, independently of autophagosomal degradation. Neurons can secrete protein aggregates via vesicles called exophers. Inhibiting neuronal early-acting autophagy genes, except atg-16.2, increased exopher formation and exopher events extended lifespan, suggesting exophers promote organismal fitness. Lifespan extension, reduction in PolyQ aggregates and increase in exophers were absent in atg-16.2 null mutants, and restored by full-length ATG-16.2 expression in neurons, but not by ATG-16.2 lacking its WD40 domain, which mediates noncanonical functions in mammalian systems. We discovered a neuronal role for C. elegans ATG-16.2 and its WD40 domain in lifespan, proteostasis and exopher biogenesis. Our findings suggest noncanonical functions for select autophagy genes in both exopher formation and in aging., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Hematopoietic stem cell transplantation (HSCT) is a common and effective treatment for multiple malignant and non-malignant pediatric conditions. Graft-versus-host disease (GVHD) is a common complication of HSCT that can be prevented with prophylactic use of calcineurin inhibitor (CNI) immunosuppressants. A complication of HSCT and CNI use is pericardial effusion (PEF), which is frequently treated by CNI discontinuation with or without surgical intervention. No studies to date have evaluated the management of PEF without CNI discontinuation as a means of preventing GVHD flares., Methods: In this single-center retrospective study, we reviewed the management of PEF in pediatric patients post-HSCT who received conservative or surgical intervention with or without CNI discontinuation between May 2012 and June 2022., Results: Of the patients found to have PEF, all were given tacrolimus for GVHD prophylaxis. Management of PEF included surgical intervention for 83% of patients, and CNI was not discontinued for 83%. None of the patients developed GVHD during the management of PEF., Conclusions: Our results demonstrate that continuation of CNI therapy for GVHD prophylaxis did not negatively impact the disease course of PEF in post-HSCT patients., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Women demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer's disease. However, the genetic underpinnings of this sex difference in memory performance remain unclear., Methods: We conducted the largest sex-aware genetic study on late-life memory to date (N males  = 11,942; N females  = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants., Results: We identified three sex-specific loci (rs67099044-CBLN2, rs719070-SCHIP1/IQCJ-SCHIP), including an X-chromosome locus (rs5935633-EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex-specific pathway and found sex-specific genetic correlations between memory and cardiovascular, immune, and education traits., Discussion: This study showed memory is highly and comparably heritable across sexes, as well as highlighted novel sex-specific genes, pathways, and genetic correlations that related to late-life memory., Highlights: Demonstrated the heritable component of late-life memory is similar across sexes. Identified two genetic loci with a sex-interaction with baseline memory. Identified an X-chromosome locus associated with memory decline in females. Highlighted sex-specific candidate genes and pathways associated with memory. Revealed sex-specific shared genetic architecture between memory and complex traits., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Diabetic foot ulcer (DFU) is a major debilitating complication of diabetes. The lack of effective diabetic wound dressings has been a significant problem in DFU management. In this study, we aim to establish a phlorotannin-incorporated nanofibre system and determine its potential in accelerating hyperglycaemic wound healing., Methods: The effective dose of Ecklonia cava phlorotannins (ECP) for hyperglycaemic wound healing was determined prior to phlorotannin nanofibre fabrication using polyvinyl-alcohol (PVA), polyvinylpyrrolidone (PVP), and ECP. Vapour glutaraldehyde was used for crosslinking of the PVA/PVP nanofibres. The phlorotannin nanofibres were characterised, and their safety and cytocompatibility were validated. Next, the wound healing effect of phlorotannin nanofibres was determined with 2D wound scratch assay, whereas immunofluorescence staining of Collagen-I (Col-I) and Cytokeratin-14 (CK-14) was performed in human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK), respectively., Results: Our results demonstrated that 0.01 μg/mL ECP significantly improved hyperglycaemic wound healing without compromising cell viability and proliferation. Among all nanofibres, PVA/PVP/0.01 wt% ECP nanofibres exhibited the best hyperglycaemic wound healing effect. They displayed a diameter of 334.7 ± 10.1 nm, a porosity of 40.7 ± 3.3%, and a WVTR of 1718.1 ± 32.3 g/m 2 /day. Besides, the FTIR spectra and phlorotannin release profile validated the successful vapour glutaraldehyde crosslinking and ECP incorporation. We also demonstrated the potential of phlorotannin nanofibres as a non-cytotoxic wound dressing as they support the viability and proliferation of both HDF and HEK. Furthermore, phlorotannin nanofibres significantly ameliorated the impaired hyperglycaemic wound healing and restored the hyperglycaemic-induced Col-I reduction in HDF., Conclusion: Taken together, our findings show that phlorotannin nanofibres have the potential to be used as a diabetic wound dressing., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

Background: Patient and public involvement (PPI) is a critical priority in research, policy, academia and advocacy organizations. PPI in dementia research is gaining momentum. However, these efforts are missing in international projects aimed at those living with advanced dementia in long-term care (LTC) homes. Additional complexities can arise in enacting PPI within the context of integration of a palliative approach to care and experiences around end-of-life in (EOL) dementia. The mySupport study involved implementing the Family Carer Decision Support (FCDS) intervention for care partners of those living with advanced dementia in LTC in six countries., Research Design and Objective: An interpretive description study was conducted to explore the perspectives of international researchers from six countries on engaging people with lived experiences of dementia and EOL care in research processes. The findings from this study informed the development of a PPI strategy and a subsequent toolkit for the FCDS intervention., Findings: Thirty-eight interviews were completed with project researchers: 12 from the United Kingdom, 8 from Canada, 7 from Ireland, 4 each from Italy and The Netherlands and 3 from the Czech Republic. Four broad themes describe international researchers' perspectives on advancing methods of engagement for people with lived experiences of dementia and EOL in international PPI activities: (1) Groundwork to engage in research; (2) planning for research activities is key; (3) focus on meaningful engagement and (4) having foresight for practical issues shaping PPI., Discussion and Implications: International projects that involve PPI can present many sources of challenges. The findings in this study highlight important considerations for foundational work for incorporating PPI in international projects. Learning from world leaders and those with lived experiences in various regions can be insightful and help share tools and resources., Patient or Public Contribution: PPI was envisioned as a critical part of conducting the mySupport study. The findings from this study informed the development of a PPI strategy and an international Strategic Guiding Council that included family carers of those living with advanced dementia in LTC homes in six countries. This manuscript focused on the perspectives of researchers on their engagement with people with lived experiences of dementia and EOL. The perspectives of persons with lived experiences on engaging in the mySupport research study will be reported in a forthcoming manuscript., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The COVID-19 pandemic led to increased telehealth utilization in outpatient otolaryngology settings. While other studies on telehealth usage in otolaryngology settings have focused on demographic disparities during the pandemic, none have yet assessed how these demographic disparities have evolved from before versus after the pandemic. This study examines 4 recent consecutive years of demographic and clinical data from a large hospital system to investigate how the COVID-19 pandemic has changed demographic patterns in telehealth utilization. We demonstrate substantial increases in the number of otolaryngology patients participating in telehealth since the beginning of the COVID-19 pandemic but with no differences in patient distributions by race or ethnicity over time. We also found that telehealth patients, on average, were younger, more likely to be English-speaking, and more likely to be female. While these disparities widened slightly after the start of the pandemic, they were also present prior to the pandemic., Competing Interests: None., (© 2024 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Introduction: Pharmacological strategies are often central to chronic pain management; however, pain treatment among non-Hispanic Black men may differ because of their disease profiles and healthcare interactions. However, less is known about pain medication prescribing and patients' satisfaction with pain treatment and management among non-Hispanic Black men with self-reported chronic pain., Purpose: This study assessed factors associated with non-Hispanic Black men being prescribed/recommended narcotics/opioids for chronic pain and their satisfaction with pain treatment/management., Methods: Data were analyzed from 286 non-Hispanic Black men with chronic pain who completed an internet-delivered questionnaire. Participants were recruited nationwide using a Qualtrics web-based panel. Logistic regression was used to identify factors associated with being prescribed/recommended narcotics/opioids for pain management treatment. Then, ordinary least squares regression was used to identify factors associated with their satisfaction level with the pain treatment/management received., Results: On average, participants were 56.2 years old and 48.3% were prescribed/recommended narcotics/opioids for chronic pain. Men with more chronic conditions (Odds Ratio [OR] = 0.57, P = 0.043) and depression/anxiety disorders (OR = 0.53, P = 0.029) were less likely to be prescribed/recommended narcotics/opioids. Men who were more educated (OR = 2.09, P = 0.044), reported more frequent chronic pain (OR = 1.28, P = 0.007), and were allowed to participate more in decisions about their pain treatment/management (OR = 1.11, P = 0.029) were more likely to be prescribed/recommended narcotics/opioids. On average, men with more frequent chronic pain (B = -0.25, P = 0.015) and pain problems (B = -0.16, P = 0.009) were less satisfied with their pain treatment/management. Men who were allowed to participate more in decisions about their pain treatment/management reported higher satisfaction with their pain treatment/management (B = 0.55, P < 0.001)., Conclusion: Playing an active role in pain management can improve non-Hispanic Black men's satisfaction with pain treatment/management. This study illustrates the importance of patient-centered approaches and inclusive patient-provider interactions to improve chronic pain management., Competing Interests: The authors have no conflicts of interest to disclose., (© 2024 Oloruntoba et al.)

Immunosuppressed kidney transplant (KT) recipients produce a weaker response to COVID-19 vaccination than immunocompetent individuals. We tested antiviral IgG response in 99 KT recipients and 66 healthy volunteers who were vaccinated with mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech vaccines. A subgroup of participants had their peripheral blood leukocytes (PBLs) evaluated for the frequency of T helper 1 (Th1) cells producing IL-2, IFN-γ and/or TNF-α, and IL-10-producing T-regulatory 1 (Tr) cells. Among KT recipients, 45.8% had anti-SARS-CoV-2 IgG compared to 74.1% of healthy volunteers ( p = 0.009); also, anti-viral IgG levels were lower in recipients than in volunteers ( p = 0.001). In terms of non-responders (≤2000 U/mL IgG), Moderna's group had 10.8% and Pfizer-BioNTech's group had 34.3% of non-responders at 6 months ( p = 0.023); similarly, 15.7% and 31.3% were non-responders in Moderna and Pfizer-BioNTech groups at 12 months, respectively ( p = 0.067). There were no non-responders among controls. Healthy volunteers had higher Th1 levels than KT recipients, while Moderna produced a higher Th1 response than Pfizer-BioNTech. In contrast, the Pfizer-BioNTech vaccine induced a higher Tr1 response than the Moderna vaccine ( p < 0.05); overall, IgG levels correlated with Th1(fT TNF-α )/Tr1(fT IL-10 ) ratios. We propose that the higher number of non-responders in the Pfizer-BioNTech group than the Moderna group was caused by a more potent activity of regulatory Tr1 cells in KT recipients vaccinated with the Pfizer-BioNTech vaccine.

Cancer is the second leading cause of death attributed to disease worldwide. Current standard detection methods often rely on a single cancer marker, which can lead to inaccurate results, including false negatives, and an inability to detect multiple cancers simultaneously. Here, we developed a multiplex method that can effectively detect and classify surface proteins associated with three distinct types of breast cancer by utilizing gap-enhanced Raman scattering nanotags and machine learning algorithm. We synthesized anisotropic magnetic core-gold shell gap-enhanced Raman nanotags incorporating three different Raman reporters. These multicolor Raman nanotags were employed to distinguish specific surface protein markers in breast cancer cells. The acquired signals were deconvoluted and analyzed using classical least-squares regression to generate a surface protein profile and characterize the breast cancer cells. Furthermore, computational data obtained via finite-difference time-domain and discrete dipole approximation showed the amplification of the electric fields within the gap region due to plasmonic coupling between the two gold layers. Finally, a random forest classifier achieved an impressive classification and profiling accuracy of 93.9%, enabling effective distinguishing between the three different types of breast cancer cell lines in a mixed solution. With the combination of immunomagnetic multiplex target specificity and separation, gap-enhancement Raman nanotags, and machine learning, our method provides an accurate and integrated platform to profile and classify different cancer cells, giving implications for identification of the origin of circulating tumor cells in the blood system.

Protein-protein interactions (PPIs) play a central role in nearly all cellular processes. The strength of the binding in a PPI is characterized by the binding affinity (BA) and is a key factor in controlling protein-protein complex formation and defining the structure-function relationship. Despite advancements in understanding protein-protein binding, much remains unknown about the interfacial region and its association with BA. New models are needed to predict BA with improved accuracy for therapeutic design. Here, we use machine learning approaches to examine how well different types of interfacial contacts can be used to predict experimentally determined BA and to reveal the impact of the specific amino acids at the binding interface on BA. We create a series of multivariate linear regression models incorporating different contact features at both residue and atomic levels and examine how different methods of identifying and characterizing these properties impact the performance of these models. Particularly, we introduce a new and simple approach to predict BA based on the quantities of specific amino acids at the protein-protein interface. We found that the numbers of specific amino acids at the protein-protein interface were correlated with BA. We show that the interfacial numbers of amino acids can be used to produce models with consistently good performance across different data sets, indicating the importance of the identities of interfacial amino acids in underlying BA. When trained on a diverse set of complexes from two benchmark data sets, the best performing BA model was generated with an explicit linear equation involving six amino acids. Tyrosine, in particular, was identified as the key amino acid in controlling BA, as it had the strongest correlation with BA and was consistently identified as the most important amino acid in feature importance studies. Glycine and serine were identified as the next two most important amino acids in predicting BA. The results from this study further our understanding of PPIs and can be used to make improved predictions of BA, giving them implications for drug design and screening in the pharmaceutical industry., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Here we report preliminary data demonstrating that some patients with myalgic encephalomyelitis/chronic fatiguesyndrome (ME/CFS) may have catalytic autoantibodies that cause the breakdown of myelin basic protein (MBP). We propose that these MBP-degradative antibodies are important to the pathophysiology of ME/CFS, particularly in the occurrence of white matter disease/demyelination. This is supported by magnetic resonance imagining studies that show these findings in patients with ME/CFS and could explain symptoms of nerve pain and muscle weakness. In this work, we performed a series of experiments on patient plasma samples where we isolated and characterized substrate-specific antibodies that digest MBP. We also tested glatiramer acetate (copaxone), an FDA approved immunomodulator to treat multiple sclerosis, and found that it inhibits ME/CFS antibody digestion of MBP. Furthermore, we found that aprotinin, which is a specific serine protease inhibitor, specifically prevents breakdown of MBP while the other classes of protease inhibitors had no effect. This coincides with the published literature describing catalytic antibodies as having serine protease-like activity. Postpandemic research has also provided several reports of demyelination in COVID-19. Because COVID-19 has been described as a trigger for ME/CFS, demyelination could play a bigger role in patient symptoms for those recently diagnosed with ME/CFS. Therefore, by studying proteolytic antibodies in ME/CFS, their target substrates, and inhibitors, a new mechanism of action could lead to better treatment and a possible cure for the disease.

Background and Aims: The 30-day readmission rate is a nationally recognized quality measure with nearly one-fifth of patients being readmitted. This study aims to evaluate frailty, as measured by the hospital frailty risk score (HFRS), as a prognostic indicator for 30-day readmission after inpatient ERCP., Methods: We analyzed weighted discharge records from the 2017 Nationwide Readmissions Database (NRD) to identify patients undergoing ERCP between 01/01/2017 and 11/30/2017. Our primary outcome was the 30-day unplanned readmission rate in frail (defined as HFRS > 5) against non-frail (HFRS < 5) patients. A mixed effects multivariable logistic regression method was employed., Results: Among 68,206 weighted hospitalized patients undergoing ERCP, 31.3% were frail. Frailty was associated with higher 30-day readmission (OR 1.23, 95% CI [1.16-1.30]). Multivariable analysis showed a greater risk of readmission with cirrhosis (OR 1.26, 95% CI [1.10-1.45]), liver transplantation (OR 1.36, 95% CI [1.08-1.71]), cancer (OR 1.58, 95% CI [1.48-1.69]), and male gender (OR 1.24, 95% CI [1.18-1.31]). Frail patients also had higher mortality rate (1.8% vs 0.6%, p < 0.01)], longer LOS during readmission (6.7 vs 5.6 days, p < 0.01), and incurred more charges from both hospitalizations ($175,620 vs $132,519, p < 0.01). Sepsis was the most common primary indication for both frail and non-frail readmissions but accounted for a greater percentage of frail readmissions (17.9% vs 12.4%, p < 0.01)., Conclusions: Frailty is associated with higher readmission rates, mortality, LOS, and hospital charges for admitted patients undergoing ERCP. Sepsis is the leading cause for readmission. Independent risk factors for readmission include liver transplantation, cancer, cirrhosis, and male gender., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Photodynamic therapy (PDT) has recently emerged as a potential valuable alternative to treat microbial infections. In PDT, singlet oxygen is generated in the presence of photosensitisers and oxygen under light irradiation of a specific wavelength, causing cytotoxic damage to bacteria. This review highlights different generations of photosensitisers and the common characteristics of ideal photosensitisers. It also focuses on the emergence of ruthenium and more specifically on Ru(II) polypyridyl complexes as metal-based photosensitisers used in antimicrobial photodynamic therapy (aPDT). Their photochemical and photophysical properties as well as structures are discussed while relating them to their phototoxicity. The use of Ru(II) complexes with recent advancements such as nanoformulations, combinatory therapy and photothermal therapy to improve on previous shortcomings of the complexes are outlined. Future perspectives of these complexes used in two-photon PDT, photoacoustic imaging and sonotherapy are also discussed. This review covers the literature published from 2017 to 2023., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Type 2 diabetes impacts millions and poor maintenance of diabetes can lead to preventable complications, which is why achieving and maintaining target A1C levels is critical. Thus, we aimed to examine inequities in A1C over time, place, and individual characteristics, given known inequities across these indicators and the need to provide continued surveillance., Methods: Secondary de-identified data from medical claims from a single payer in Texas was merged with population health data. Generalized Estimating Equations were utilized to assess multiple years of data examining the likelihood of having non-target (>7% and ≥7%, two slightly different cut points based on different sources) and separately uncontrolled (>9%) A1C. Adults in Texas, with a Type 2 Diabetes (T2D) flag and with A1C reported in first quarter of the year using data from 2016 and 2019 were included in analyses., Results: Approximately 50% had A1Cs within target ranges (<7% and ≤7%), with 50% considered having non-target (>7% and ≥7%) A1Cs; with 83% within the controlled ranges (≤9%) as compared to approximately 17% having uncontrolled (>9%) A1Cs. The likelihood of non-target A1C was higher among those individuals residing in rural (vs urban) areas ( P  < .0001); similar for the likelihood of reporting uncontrolled A1C, where those in rural areas were more likely to report uncontrolled A1C ( P  < .0001). In adjusted analysis, ACA enrollees in 2016 were approx. 5% more likely (OR = 1.049, 95% CI = 1.002-1.099) to have non-target A1C (≥7%) compared to 2019; in contrast non-ACA enrollees were approx. 4% more likely to have non-target A1C (≥7%) in 2019 compared to 2016 (OR = 1.039, 95% CI = 1.001-1.079). In adjusted analysis, ACA enrollees in 2016 were 9% more likely (OR = 1.093, 95% CI = 1.025-1.164) to have uncontrolled A1C compared to 2019; whereas there was no significant change among non-ACA enrollees., Conclusions: This study can inform health care interactions in diabetes care settings and help health policy makers explore strategies to reduce health inequities among patients with diabetes. Key partners should consider interventions to aid those enrolled in ACA plans, those in rural and border areas, and who may have coexisting health inequities., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Precision engineering of the gut microbiome holds promise as an effective therapeutic approach for diseases associated with a disruption in this microbial community. Engrafting a live biotherapeutic product (LBP) in a predictable, controllable manner is key to the consistent success of this approach and has remained a challenge for most LBPs under development. We recently demonstrated high-level engraftment of Bifidobacterium longum subsp. infantis (B. infantis ) in adults when co-dosed with a specific prebiotic, human milk oligosaccharides (HMO). Here, we present a cellular kinetic-pharmacodynamic approach, analogous to pharmacokinetic-pharmacodynamic-based analyses of small molecule- and biologic-based drugs, to establish how HMO controls expansion, abundance, and metabolic output of B. infantis in a human microbiota-based model in gnotobiotic mice. Our data demonstrate that the HMO dose controls steady-state abundance of B. infantis in the microbiome, and that B. infantis together with HMO impacts gut metabolite levels in a targeted, HMO-dependent manner. We also found that HMO creates a privileged niche for B. infantis expansion across a 5-log range of bacterial inocula. These results demonstrate remarkable control of both B. infantis levels and the microbiome community metabolic outputs using this synbiotic approach, and pave the way for precision engineering of desirable microbes and metabolites to treat a range of diseases.

Uveitis masquerade syndromes are a diverse group of clinical entities which mimic conventional immune-mediated uveitis due to the presence of inflammatory signs but are resistant to anti-inflammatory therapy. Misdiagnosis hinders appropriate management in these conditions and may result in poor outcomes. This review discusses commonly encountered neoplastic and non-neoplastic disease processes that masquerade as intraocular inflammation with a focus on relevant clinical features and adjunctive investigations that are helpful in reaching a correct diagnosis., (© 2023 Royal Australian and New Zealand College of Ophthalmologists.)

Objective: To develop and psychometrically evaluate an adapted version of the Female Self-Advocacy in Cancer Survivorship (FSACS) Scale in men with a history of cancer., Methods: This psychometric instrument development and validation study used a two-phase approach to first adapt the FSACS Scale items to reflect the experience of men with a history of cancer and then evaluate the psychometric properties of the adapted scale compared to the original FSACS Scale. The study was conducted from December 2018 through April 2022 through cancer clinics, patient registries, and national advocacy organizations. We evaluated scale reliability and validity using reliability coefficients, exploratory and confirmatory factor analyses, and item analyses to determine a final set of scale items., Results: Item responses from N = 171 men with a history of cancer were evaluated to determine scale validity. After removing poor-performing items based on item-level analyses, factor analyses confirmed that a 3-factor structure of both the adapted and original FSACS Scale best fit the scale. The 10 new items did not outperform the original 20-item scale and were therefore excluded from the final scale. The final 20-item scale explained 87.94% of item variance and subscale's Cronbach α varied from 0.65 to 0.86., Conclusion: The SACS Scale can be used in research and clinical contexts to assess the propensity of men and women to get their needs, values, and priorities met in the face of a challenge., (© 2023 John Wiley & Sons Ltd.)

Objective: Precision medicine is an area with great potential for mental health, but has made limited gains prognostically in predicting effective treatments. For refugees exposed to violence, culture may be a crucial factor in predicting treatment outcomes., Method: For this study, 290 participants from three regions (Afghanistan, the Great Lakes region of Africa, and Iraq and Syria) participated in a randomized controlled trial of an advocacy-based intervention. Emotional distress symptoms were measured prior to intervention, midintervention (3 months), postintervention (6 months), and follow-up (6 months after the end of intervention). Number of traumatic events, resource access, social support, and English proficiency were tested for potential predictive effects on intervention outcome., Results: Multilevel generalized linear models revealed that Afghans' ( B = -0.259, SE = 0.108, p = .013), and Great Lakes Africans' ( B = -0.116, SE = 0.057, p = .042) emotional distress symptoms improved as a function of the intervention, while Iraqis and Syrians showed no intervention effects. For Afghans, English proficiency ( B = -0.453, SE = 0.157, p < .01) and social support ( B = -0.179, SE = 0.086, p = .037) were most strongly correlated to emotional distress, while for Africans, resource access ( B = -0.483, SE = 0.082, p < .001) and social support ( B = -0.100, SE = 0.048, p = .040) were the strongest predictors of emotional distress., Conclusions: Response to advocacy-based interventions and active ingredients may be influenced by culture; findings have implications for refugees and precision medicine. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background and Objectives: Strategies to manage the coronavirus disease 2019 (COVID-19) pandemic included widespread use of physical distancing measures. These well-intended strategies adversely affected long-term care (LTC) residents' socialization and their caregiving arrangements, leading to exacerbation of social isolation and emotional distress for both residents and their caregivers. This study aimed to understand how these measures affected informal caregivers of people living in LTC homes in Ontario. Strategies to increase socialization and promote social connection during and post-COVID-19 were also explored., Research Design and Methods: This qualitative study used descriptive and photovoice approaches. Of the 9 potential caregivers identified, 6 participated in the study and shared their experiences and photographic reflections in virtual focus group sessions., Results: Findings highlighted the increased social isolation experienced by people living in LTC and their caregivers during COVID-19. Caregivers reported pronounced declines in residents' well-being and were frustrated by challenges connecting with their family members during quarantine. Attempts made by LTC homes to maintain social connections, such as window visits and video calls, did not fulfill the social needs of residents and their caregivers., Discussion and Implications: Findings underscore a need for better social support and resources for both LTC residents and their caregivers going forward to prevent further isolation and disengagement. Even in times of lockdown, LTC homes must implement policies, services, and programs that promote meaningful engagement for older adults and their families., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Joint replacement is a common surgery and is predominantly utilized for treatment of osteoarthritis in the aging population. The longevity of many of these implants depends on bony ingrowth. Here, we provide an overview of current techniques in osteogenesis (inducing bone growth onto an implant), which is affected by aging and inflammation. In this review we cover the biologic underpinnings of these processes as well as the clinical applications. Overall, aging has a significant effect at the cellular and macroscopic level that impacts osteosynthesis at bone-metal interfaces after joint arthroplasty; potential solutions include targeting prolonged inflammation, preventing microbial adhesion, and enhancing osteoinductive and osteoconductive properties.

Objective: Fear of Cancer Recurrence (FCR) is highly prevalent among cancer survivors and leads to decreased quality of life and increased healthcare costs. We assessed the effectiveness of a guided online primary care intervention for FCR, compared to waiting list., Methods: In this RCT, participants were recruited online and randomised 1:1. All adults who finished successful curative cancer treatment between 3 months and 10 years ago, wanted support for FCR, and had sufficient Dutch skills were eligible. The intervention consisted of a 10-week online programme and three to five video calling sessions with a trained mental health worker. After 6 months, the control group received the same intervention. The primary outcome was the difference between the groups in the change in FCR severity from baseline (T0) to 6 months (T2), measured online with the short form of the Fear of Cancer Recurrence Inventory., Results: One hundred and seventy-three participants were enroled and randomised to the intervention (n = 86) or control group (n = 87). FCR severity dropped 2.1 points more in the intervention group than in the control group (2.7 points (SD = 3.9) versus 0.6 points (SD = 3.6), t(154) = 3.4, p = 0.0007). General mental well-being also improved significantly in the intervention group and remained stable in the control group. These improvements remained at 10 months follow up., Conclusions: This easily accessible and relatively inexpensive intervention effectively reduces FCR and has potential to replace or precede existing more intensive psychological treatments, improving patients' access to care., Trial Registration: The trial was prospectively registered in the Netherlands Trial Register on 25-02-2019 with number NL7573., (© 2023 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Objective: Issues regarding clinician communication remain an important source of complaints within healthcare. This systematic review aims to determine cancer patients' and their family caregivers' views on which clinicians' communication behaviors can harm (i.e. eliciting negative feelings/consequences for patients/family caregivers)., Methods: We searched for all types of peer-reviewed studies that determined adult (≥18 years) cancer patients' and/or family caregivers' perspectives on which clinicians' communication behaviors can harm in several databases (PubMed, Embase, Web of Science, Cochrane Library, Emcare, PsycINFO and Academic Search Premier), supplemented by expert-consultation. Studies were screened using the Artificial intelligence screening tool of ASReview and data was analyzed using Thematic Analysis. To assess the quality of the studies the Qualsyst critical appraisal tool was used., Results: A total of 47 studies were included. Four main themes of harmful communication behaviors were identified: (1) Lack of tailored information provision (e.g. giving too little or too much/specific information) (2) Lack of tailored decision making (ranging from; patient exclusion, to the patients' responsibility, and/or haste) (3) Lack of feeling seen and heard (seen as a disease, not as a human being; not listened to concerns and emotions) (4) Lack of feeling held and remembered (forgotten agreements; lack of care continuity)., Conclusions: Our results reveal an overview of patients' and family caregivers' perspectives on which clinicians' communication behaviors can harm. Harm could be prevented when information and decision involvement are tailored and patients' and family caregivers' needs to feel seen, heard, held and remembered are met., (© 2023 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Objective: Approximately 25% of cancer patients suffer from cancer-related fatigue (CRF) after cancer treatment. CRF is a multi-factorial condition affected by several interrelated protective and perpetuating factors. As most studies merely assessed bivariate associations, more insight into the complex relationships among these constructs is needed. We applied the multivariate network approach to gain a better understanding of how patients' fatigue, perpetuating and protective factors are dynamically interconnected., Method: Between February and August 2022, 30 cancer patients filled out a carefully developed ecological momentary assessment questionnaire (EnergyInSight) five times a day for at least 21 days while being on the waitlist for psychological care for CRF. We performed a multi-level vector autoregression analysis to examine the interconnectedness among fatigue, protective factors (allowing rest, acceptance, and self-efficacy) and perpetuating factors (worrying, catastrophizing, and feeling guilty)., Results: In the contemporaneous network (concurrent associations), higher acceptance and self-efficacy were associated with lower fatigue, whereas all other factors were associated with higher fatigue. The strongest relationships were between worrying and feeling guilty and between acceptance and allowing rest. In the temporal network (lagged associations), fatigue was related to two factors: higher self-efficacy preceded lower fatigue, and higher fatigue preceded increased allowing rest., Conclusions: Taking all included factors into account, the networks identified self-efficacy and allowing rest as key protective factors of CRF. Patients may benefit from psychological interventions that cultivate self-efficacy, as it seems to pave the way to reduced fatigue., (© 2023 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Renin-angiotensin system inhibitors (RASi), particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), are commonly used in the treatment of hypertension and are recommended for kidney protection. Uncertainty remains about the effectiveness of RASi being used as first-line antihypertensive therapy on eGFR maintenance compared to its alternatives, especially for those with no or early-stage chronic kidney disease (CKD). We conducted a retrospective cohort study of 19,499 individuals (mean age 64.1, 43.5% males) from primary care in Singapore with 4.5 median follow-up years. The study cohort included newly diagnosed individuals with hypertension (whose eGFR was mainly in CKD stages G1-G2) and initiated on ACEIs, ARBs, beta-blockers (BBs), calcium channel blockers (CCBs) or diuretics (Ds) as first-line antihypertensive monotherapy. We compared the estimated glomerular filtration rate (eGFR) curve before/after the drug initiation over time of patients under different drug classes and analyzed the time to declining to a more advanced stage CKD. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounding factors. Two key findings were observed. First, after initiating antihypertensive drugs, the eGFR almost maintained the same as the baseline in the first follow-up year, compared with dropping 3 mL/min/1.73 m 2 per year before drug initiation. Second, ARBs were observed to be slightly inferior to ACEIs (HR = 1.14, 95% CI = (1.04, 1.23)) and other antihypertensive agents (HR = 1.10, 95% CI = (1.01, 1.20)) in delaying eGFR decline to a more advanced CKD stage in the study population. Our results showed that initiating antihypertensive agents can significantly maintain eGFR for those newly diagnosed patients with hypertension. However, RASi may not be superior to other antihypertensive agents in maintaining eGFR levels for non-CKD or early stages CKD patients., (© 2023. The Author(s).)

Background and Objectives: There is conflicting evidence on the significance of adrenocorticotrophic hormone (ACTH) staining in the prognosis of nonfunctioning pituitary neuroendocrine tumors (NFpitNETs). The objective of this study was to define the effect of ACTH immunostaining on clinical and radiographic outcomes of stereotactic radiosurgery (SRS) for NFpitNETs., Methods: This retrospective, multicenter study included patients managed with SRS for NFpitNET residuals. The patients were divided into 2 cohorts: (1) silent corticotroph (SC) for NFpitNETs with positive ACTH immunostaining and (2) non-SC NFpitNETs. Rates of local tumor control and the incidence of post-treatment pituitary and neurological dysfunction were documented. Factors associated with radiological and clinical outcomes were also analyzed., Results: The cohort included 535 patients from 14 centers with 84 (15.7%) patients harboring silent corticotroph NFpitNETs (SCs). At last follow-up, local tumor progression occurred in 11.9% of patients in the SC compared with 8.1% of patients in the non-SC cohort (P = .27). No statistically significant difference was noted in new-onset hypopituitarism rates (10.7% vs 15.4%, P = .25) or visual deficits (3.6% vs 1.1%, P = .088) between the 2 cohorts at last follow-up. When controlling for residual tumor volume, maximum dose, and patient age and sex, positive ACTH immunostaining did not have a significant correlation with local tumor progression (hazard ratio = 1.69, 95% CI = 0.8-3.61, P = .17)., Conclusion: In contemporary radiosurgical practice with a single fraction dose of 8-25 Gy (median 15 Gy), ACTH immunostaining in NFpitNETs did not appear to confer a significantly reduced rate of local tumor control after SRS., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: To analyze the involvement of the posterior cingulate gyrus (PCG) during mesial temporal lobe seizures (MTLS)., Methods: We retrospectively reviewed the stereo-EEG (SEEG) recordings of patients with MTLS performed in our institution from February 2013 to December 2020. Only patients who had electrode implantation in the PCG were included. Patients with lesions that could potentially alter the seizure spread pathways were excluded. We assessed the propagation patterns of MTLS with respect to the different structures sampled., Results: Nine of 97 patients who had at least one seizure originating in the mesial temporal region met the inclusion criteria. A total of 174 seizures were analyzed. The PCG was the first site of propagation in most of the cases (8/9 patients and 77.5% of seizures, and 7/8 patients and 65.6% of seizures after excluding an outlier patient). The fastest propagation times were towards the contralateral mesial temporal region and ipsilateral PCG. Seven patients underwent standard anterior temporal lobectomy and, of these, all but one were Engel 1 at last follow up., Conclusion: We found the PCG to be the first propagation site of MTLS in this group of patients. These results outline the relevance of the PCG in SEEG planning strategies. Further investigations are needed to corroborate whether fast propagation to the PCG predicts a good surgical outcome., Competing Interests: Disclosure of interests Dr. Burneo holds the Jack Cowin Chair in Epilepsy Research from Western University. Dr. Mirsattari has received honorarium for speaking engagements for UCB Canada Inc., Eisai Co. Ltd (Canada), and Sunovion Pharmaceuticals Canada Inc. He has been member of the Epilepsy National Advisory Board for UCB Canada Inc., Eisai Co. Ltd (Canada) and Sunovion Pharmaceuticals Canada Inc. Dr. Steven receives educational funds from Livanova and receives speaker fees from UCB Canada and Medtronic Canada. Dr. Lee-Jones receives unrestricted educational grants from UCB and Sunovion. The remaining authors have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diabetic wounds are slow healing wounds characterized by disordered healing processes and frequently take longer than three months to heal. One of the defining characteristics of impaired diabetic wound healing is an abnormal and unresolved inflammatory response, which is primarily brought on by abnormal macrophage innate immune signaling activation. The persistent inflammatory state in a diabetic wound may be attributed to inflammatory pathways such as nuclear factor kappa B (NF-ĸB) and nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which have long been associated with inflammatory diseases. Despite the available treatments for diabetic foot ulcers (DFUs) that include debridement, growth factor therapy, and topical anti-bacterial agents, successful wound healing is still hampered. Further understanding of the molecular mechanism of these pathways could be useful in designing potential therapeutic targets for diabetic wound healing. This review provides an update and novel insights into the roles of NF-ĸB and NLRP3 pathways in the molecular mechanism of diabetic wound inflammation and their potential as therapeutic targets in diabetic wound healing., 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 © 2023. Published by Elsevier Inc.)

Evidence on the influence of patient characteristics on HbA 1c treatment response for add-on medications in patients with type 2 diabetes (T2D) is unclear. This study aims to investigate the predictors of HbA 1c treatment response for three add-on medications (sulfonylureas (SU), dipeptidyl peptidase-4 (DPP-4) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor) in metformin monotherapy treated patients with T2D. This retrospective cohort study was conducted using the electronic health record data from six primary care clinics in Singapore. A total of 9748 adult patients with T2D on metformin monotherapy receiving SU, DPP-4 or SGLT-2 add-on were 1:1 propensity score matched to patients receiving other add-on medications. Patient demographics, laboratory results, diabetes related complications, comedications, and treatment response at two endpoints (HbA 1c reduction ≥ 1% at 6th month, HbA 1c goal attainment < 7% at 12th month) were examined. Multiple logistic regression analyses were used to identify patient characteristics associated with the treatment responses. After matching, there were 1073, 517, and 290 paired cohorts of SU, DPP-4 and SGLT-2 respectively. Besides baseline HbA 1c , patients with longer hypertension disease duration and higher cholesterol HDL were associated with better treatment response to SU medication add-on. Lower estimated glomerular filtration rate (eGFR), and angiotensin-II receptor medications were associated with better treatment response to DPP-4 add-on. Lower cholesterol HDL, higher creatinine serum, absence of renal complications and beta-blockers medications were associated with better treatment response to SGLT-2 add-on. The cholesterol HDL, creatinine serum, eGFR, hypertension disease duration, angiotensin-II receptors and beta-blockers class of medications can influence the HbA 1c treatment response for SU, DPP-4 and SGLT-2 add-on medications. Knowing the patients' characteristics that influence treatment response can assist in guiding clinical decisions when selecting the appropriate add-on medication, ultimately helping to prevent the development of diabetes-related complications., (© 2023. The Author(s).)

Local cell therapy has recently gained attention for the treatment of joint diseases and fractures. Mesenchymal stem cells (MSCs) are not only involved in osteogenesis and angiogenesis, but they also have immunomodulatory functions, such as inducing macrophage migration during bone regeneration via macrophage crosstalk. C-C motif chemokine ligand 2 (CCL2), a known inflammatory mediator, is associated with the migration of macrophages during inflammation. This study examined the utility of CCL2 as a therapeutic target for local cell therapy. Using lentiviral vectors for rabbit MSCs, genetically modified CCL2 overexpressing MSCs were generated. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture, and cell migration assays were also performed. Additionally, co-cultures were performed with endothelial cells (ECs), and angiogenesis was evaluated using a tube formation assay. Overexpression of CCL2 did not affect bone formation under monoculture conditions but promoted chemotaxis and osteogenesis when co-cultured with macrophages. Furthermore, CCL2 -overexpression promoted tube formation in co-culture with ECs. These results suggest that CCL2 induces macrophage chemotaxis and osteogenesis by promoting crosstalk between MSCs and macrophages; CCL2 also stimulates ECs to induce angiogenesis. These findings indicate that CCL2 may be a useful therapeutic target for local cell therapy in areas of bone loss.

Objective: To develop a deep learning algorithm (DLA) to detect diabetic kideny disease (DKD) from retinal photographs of patients with diabetes, and evaluate performance in multiethnic populations., Materials and Methods: We trained 3 models: (1) image-only; (2) risk factor (RF)-only multivariable logistic regression (LR) model adjusted for age, sex, ethnicity, diabetes duration, HbA1c, systolic blood pressure; (3) hybrid multivariable LR model combining RF data and standardized z-scores from image-only model. Data from Singapore Integrated Diabetic Retinopathy Program (SiDRP) were used to develop (6066 participants with diabetes, primary-care-based) and internally validate (5-fold cross-validation) the models. External testing on 2 independent datasets: (1) Singapore Epidemiology of Eye Diseases (SEED) study (1885 participants with diabetes, population-based); (2) Singapore Macroangiopathy and Microvascular Reactivity in Type 2 Diabetes (SMART2D) (439 participants with diabetes, cross-sectional) in Singapore. Supplementary external testing on 2 Caucasian cohorts: (3) Australian Eye and Heart Study (AHES) (460 participants with diabetes, cross-sectional) and (4) Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) (265 participants with diabetes, cross-sectional)., Results: In SiDRP validation, area under the curve (AUC) was 0.826(95% CI 0.818-0.833) for image-only, 0.847(0.840-0.854) for RF-only, and 0.866(0.859-0.872) for hybrid. Estimates with SEED were 0.764(0.743-0.785) for image-only, 0.802(0.783-0.822) for RF-only, and 0.828(0.810-0.846) for hybrid. In SMART2D, AUC was 0.726(0.686-0.765) for image-only, 0.701(0.660-0.741) in RF-only, 0.761(0.724-0.797) for hybrid., Discussion and Conclusion: There is potential for DLA using retinal images as a screening adjunct for DKD among individuals with diabetes. This can value-add to existing DLA systems which diagnose diabetic retinopathy from retinal images, facilitating primary screening for DKD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Context: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized., Objective: To analyze postoperative serum cortisol and recurrence rates in Cushing disease., Methods: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables., Results: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001)., Conclusion: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Adult chimpanzees Tatu and Loulis lived at the Fauna Foundation sanctuary. They had acquired signs of American Sign Language (ASL) while young and continued to use them as adults. Caregivers with proficiency in ASL maintained daily sign language records during interactions and passive observation. Sign checklists were records of daily vocabulary use. Sign logs were records of signed interactions with caregivers and other chimpanzees. This study reports sign use from eight years of these records. Tatu and Loulis used a majority of their base vocabularies consistently over the study period. They used signs that they had acquired decades earlier and new signs. Their utterances served a variety of communicative functions, including responses, conversational devices, requests, and descriptions. They signed to caregivers, other chimpanzees, including those who did not use signs, and to themselves privately. This indicates the importance of a stimulating and interactive environment to understand the scope of ape communication and, in particular, their use of sign language.

Purpose: Although identified as a key competency domain and a needed area of professional development, interpersonal communication in breast cancer care patient navigation is understudied. Moreover, the patient-navigator relationship may be influenced by the interpersonal communication skills and behaviors of the patient navigator. This paper reports on the interpretation step of a concept mapping study, where key stakeholders shared their perspectives on six identified interpersonal communication components of breast cancer care patient navigation., Methods: This study utilized concept mapping, a community-engaged mixed method approach. After conducting brainstorming, sorting, and concept mapping analysis, a six-cluster concept map of interpersonal communication in breast cancer care patient navigation was identified. Interpretation sessions with each participant group (patients, patient navigators, administrators) allowed both naming and more in-depth exploration of the six clusters. The sessions were led by a facilitator, the PI, and were audio recorded and transcribed., Results: Six 2-h interpretation sessions were conducted with 21 participants, including patients with breast cancer, breast cancer patient navigators (lay or medically trained), and patient navigation administrators from Western Pennsylvania. Through a group consensus process, the six clusters were named. Participants identified that all six identified components were essential to patient navigation, but the ability to build patient-centered trust and relationships and maintain professional communication were the most impactful components of the patient-navigator relationship., Conclusion: These findings validate the importance of interpersonal skills and behaviors of patient navigators in breast cancer care. These findings can inform the patient navigation role description, competencies, and the development of curriculum for training and metrics for evaluation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hand trauma, comprising injuries to both the hand and wrist, affects over five million people per year in the NHS, resulting in 250 000 operations each year. Surgical site infection (SSI) following hand trauma surgery leads to significant morbidity. Triclosan-coated sutures may reduce SSI in major abdominal surgery but have never been tested in hand trauma. Feasibility needs to be ascertained before a definitive trial can be delivered in hand trauma., Methods: A multicentre feasibility RCT of antimicrobial sutures versus standard sutures involving adults undergoing surgery for hand trauma to evaluate feasibility for a definitive trial. Secondary objectives were incidence of SSI in both groups, hand function measured with patient-reported outcome measures, health-related quality of life and change in employment. Randomization was performed on a 1:1 basis, stratified by age of the patient and whether the injury was open or closed, using a secure, centralized, online randomization service. Participants were blinded to allocation., Results: 116 participants were recruited and randomized (60 intervention, 56 control). Of 227 screened, most were eligible (89.5 per cent), and most who were approached agreed to be included in the study (84.7 per cent). Retention was low: 57.5 per cent at 30 days, 52 per cent at 90 days and 45.1 per cent at 6 months. Incidence of SSI was >20 per cent in both groups. Hand function deteriorated after injury but recovered to near pre-injury levels during the study period., Conclusions: Risk of SSI after hand trauma is high. A definitive RCT of antimicrobial sutures in hand trauma surgery is feasible, if retention is improved., Trial Registration: ISRCTN10771059., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Study Objectives: To examine whether drivers are aware of sleepiness and associated symptoms, and how subjective reports predict driving impairment and physiological drowsiness., Methods: Sixteen shift workers (19-65 years; 9 women) drove an instrumented vehicle for 2 hours on a closed-loop track after a night of sleep and a night of work. Subjective sleepiness/symptoms were rated every 15 minutes. Severe and moderate driving impairment was defined by emergency brake maneuvers and lane deviations, respectively. Physiological drowsiness was defined by eye closures (Johns drowsiness scores) and EEG-based microsleep events., Results: All subjective ratings increased post night-shift (p < 0.001). No severe drive events occurred without noticeable symptoms beforehand. All subjective sleepiness ratings, and specific symptoms, predicted a severe (emergency brake) driving event occurring in the next 15 minutes (OR: 1.76-2.4, AUC > 0.81, p < 0.009), except "head dropping down". Karolinska Sleepiness Scale (KSS), ocular symptoms, difficulty keeping to center of the road, and nodding off to sleep, were associated with a lane deviation in the next 15 minutes (OR: 1.17-1.24, p<0.029), although accuracy was only "fair" (AUC 0.59-0.65). All sleepiness ratings predicted severe ocular-based drowsiness (OR: 1.30-2.81, p < 0.001), with very good-to-excellent accuracy (AUC > 0.8), while moderate ocular-based drowsiness was predicted with fair-to-good accuracy (AUC > 0.62). KSS, likelihood of falling asleep, ocular symptoms, and "nodding off" predicted microsleep events, with fair-to-good accuracy (AUC 0.65-0.73)., Conclusions: Drivers are aware of sleepiness, and many self-reported sleepiness symptoms predicted subsequent driving impairment/physiological drowsiness. Drivers should self-assess a wide range of sleepiness symptoms and stop driving when these occur to reduce the escalating risk of road crashes due to drowsiness., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

Human serum albumin (HSA) efficiently transports drugs in vivo: most are organic. Therefore, it is important to delineate the binding of small molecules to HSA. Here, for the first time, we show that HSA binding depends not only on the identity of the d 8 metal ion, Ni II or Pd II , of their complexes with bis(pyrrole-imine), H 2 PrPyrr, but on the pH level as well. Fluorescence quenching data for native and probe-bound HSA showed that sites close to Trp-214 (subdomain IIA) are targeted. The affinity constants, K a , ranged from ~3.5 × 10 3 M -1 to ~1 × 10 6 M -1 at 37 °C, following the order Pd(PrPyrr) > Ni(PrPyrr) at pH levels of 4 and 7; but Ni(PrPyrr) > Pd(PrPyrr) at a pH level of 9. Ligand uptake is enthalpically driven, dependent mainly on London dispersion forces. The induced CD spectra for the protein-bound ligands could be simulated by hybrid QM:MM TD-DFT methods, allowing us to delineate the binding site of the ligands and to prove that the metal chelates neither decompose nor demetallate after uptake by HSA. The transport and delivery of the metal chelates by HSA in vivo is therefore feasible.

Objectives: Caregiver strain often stems from unmet needs and is a risk factor for poor physical and psychological health. This study aims to identify factors associated with caregiver strain among middle-aged and older non-Hispanic Black and Hispanic male caregivers living with one or more chronic conditions., Design: Data were analyzed from 418 male caregivers collected through Qualtrics Online Panels using an internet-delivered survey instrument (55.7% non-Hispanic Black, 44.3% Hispanic). Three ordinal regression models were fitted to assess factors associated with Caregiver Strain Scale tertiles: one for all men, one for non-Hispanic Black men only; and one for Hispanic men only., Results: Similarities and differences were observed between the two groups in terms of factors associated with higher caregiver strain (i.e. lower disease self-management efficacy scores, providing ≥20 h of care per week). Uniquely for Non-Hispanic Black male caregivers, higher caregiver strain was associated with living with more children under the age of 18 ( β  = 0.35, P  = 0.011) and feeling more socially disconnected ( β  = 0.41, P  = 0.008). Uniquely for Hispanic male caregivers, higher caregiver strain levels were associated with experiencing lower pain levels ( β  = -0.14, P  = 0.040) and higher fatigue levels ( β  = 0.23, P  < 0.001)., Conclusion: Findings from this study suggest that non-Hispanic Black and Hispanic men with chronic conditions have differing caregiving experiences. While bolstering social connectedness and caregiver support services may offset caregiver strain, tailored mental health and disease management programming are needed to meet the specific needs of non-Hispanic Black and Hispanic male caregivers.

Objectives: Although public efforts to reduce tobacco use have been successful, millions of US adults currently smoke tobacco. Reducing the public health burden of tobacco use disorder (TUD) and eliminating disparities experienced by underresourced communities requires increased accessibility to services. The goal of this study was to assess whether prescriptions for evidence-based medications for tobacco treatment showed steeper growth rates among community health clinics providing specialty TUD services as compared with treatment as usual., Methods: Clinic-wide data on prescriptions for smoking cessation pharmacotherapy at 18 primary care or mental health community clinics operated by Los Angeles County were retrieved for 4 years of an ongoing implementation trial. Specialty services included behavioral counseling and medications for tobacco treatment. Descriptive statistics characterized prescriptions rates across clinics and time. Analyses compared the slopes of the changes between intervention groups across time for primary care and mental health sites., Results: Within primary care clinics, the most commonly prescribed smoking cessation medications were nicotine patches, nicotine gum, and varenicline. Throughout the trial, all clinics displayed increased rates of prescribing smoking cessation medications. Analytic results supported overall steeper increases in prescription rates for these medications among clinics randomized to specialty services versus treatment as usual within primary care ( P = 0.020) and mental health sites ( P = 0.004)., Conclusions: This work provides support for the effectiveness of community-based implementation interventions that promote prescribing smoking cessation medications with the potential to reduce health disparities among communities at greater risk for TUD and its consequences., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

The prevalence of type 2 diabetes (T2D) is increasing among non-Hispanic Black and Hispanic communities, especially among men who develop this chronic condition at earlier ages. Personal agency and social support are vital aspects to diabetes management. However, less is known about the relationship between these variables among men living with diabetes. The purposes of this study were to identify (1) levels of personal agency to manage health, (2) sources of social supports to manage health based on personal agency levels, and (3) factors associated with lower personal agency to manage health. Cross-sectional data from non-Hispanic Black ( n = 381) and Hispanic ( n = 292) men aged 40 years or older with T2D were collected using an internet-delivered questionnaire. Three binary logistic regression models were fitted to assess sociodemographics, health indicators, and support sources associated with weaker personal agency to manage health. About 68% of participants reported having the strongest personal agency relative to 32.1% reporting weaker personal agency. Men who relied more on their spouse/partner (odds ratio [OR] = 1.22, p = .025), coworkers (OR = 1.59, p = .008), or faith-based organizations (OR = 1.29, p = .029) for ongoing help/support to improve their health and manage health problems were more likely to have weaker personal agency. Conversely, men who relied more on their health care providers for ongoing help/support to improve their health and manage health problems were less likely to have weaker personal agency to manage health (OR = 0.74, p < .001). Findings suggest personal agency may influence men's support needs to manage T2D, which may also be influenced by cultural, socioeconomics, and the composition of social networks., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.