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Purpose: To evaluate novel, automated biomarkers, pigment epithelial detachment composition indices (PEDCI) in eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy through 24 months., Methods: Retrospective analysis of 37 eyes (34 patients) with PED associated with nAMD receiving as-needed anti-VEGF treatment was performed. Best-corrected visual acuity (BCVA) and optical coherence tomography images were acquired at a treatment-naïve baseline and 3-, 6-, 12-, 18-, and 24-month visits. Previously validated automated imaging biomarkers, PEDCI-S (serous), PEDCI-N (neovascular), and PEDCI-F (fibrous) within PEDs were measured. ANOVA analysis and Spearman correlation were performed., Results: Mean BCVA (in logMAR) was 0.60 ± 0.47, 0.45 ± 0.41, 0.49 ± 0.49, 0.61 ± 0.54, 0.59 ± 0.56, and 0.67 ± 0.57 at baseline, 3, 6, 12, 18, and 24 months respectively. Overall, BCVA showed minimal worsening of 0.07 ± 0.54 logMAR (p = 0.07). 13.38 ± 3.77 anti-VEGF injections were given through 24 months. PEDCI-F showed an increase of 0.116, 0.122, 0.036, and 0.006 at months 3, 6, 12, and 18 respectively and a decrease of 0.004 at month 24 (p = 0.03); PEDCI-S showed a decrease of 0.064, 0.130, 0.091, 0.092, and 0.095 at months 3, 6, 12, 18, and 24 respectively (p = 0.16); PEDCI-N showed a decrease of 0.052 at month 3 and an increase of 0.008, 0.055, 0.086, and 0.099 at months 6, 12, 18, and 24 respectively (p = 0.06). BCVA was negatively correlated with PEDCI-F (r = -0.28, p < 0.01), and positively correlated with PEDCI-N (r = 0.28, p < 0.01) and PEDCI-S (r = 0.15, p = 0.03)., Conclusion: Longitudinal analysis of PEDCI supports their utility as biomarkers that characterize treatment related effects by quantifying the relative composition of PEDs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The strength of evidence for specific ambulatory care prescribing cascades, in which a marker drug is used to treat an adverse event caused by an index drug, has not been well characterized. To perform a structured, systematic, and transparent review of the evidence supporting ambulatory care prescribing cascades. Ninety-four potential prescribing cascades identified through a previously published systematic review. Systematic search of the literature to further characterize prescribing cascades. (1) Grading of evidence based on observational studies investigating associations between index and marker drugs, including: Level I-strong evidence [i.e. multiple high-quality studies]; Level II-moderate evidence [i.e. single high-quality study]; Level III-fair evidence [no high-quality studies but one or more moderate-quality studies]; and Level IV-poor evidence [other]. (2) Listing of the adverse event associated with the index drug in the product's United States Food and Drug Administration (FDA) label. (3) Synthesis of the evidence supporting mechanisms linking index drugs and associated adverse events. Of 99 potential cascades, 94 were supported by one or more confirmatory observational studies and were therefore included in this review. The 94 cascades related to 30 types of adverse drug reactions affecting 10 different anatomic/physiologic systems and were investigated by a total of 88 confirmatory studies, including prescription sequential symmetry analysis (n = 51), cohort (n = 30), and case-control (n = 7) studies. Overall, the evidence from observational studies was strong for 18 (19.1%) prescribing cascades, moderate for 61 (64.9%), fair for 13 (13.8%), and poor for 2 (2.1%). Although the evidence supporting mechanisms that link index drugs and associated adverse events was variable, FDA labels included information about the adverse event associated with the index drug for most (n = 86) but not all of the 94 prescribing cascades. Although we identified 18 of 94 prescribing cascades supported by strong clinical evidence and most adverse events associated with index drugs are included in FDA label, the evidentiary basis for prescribing cascades varies, with many requiring further evidence of clinical relevance., (© 2023 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)

Background: To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent., Objective: This systematic review aims to provide an overview of prescribing cascades, including dose-dependency information and recommendations that healthcare providers can use to prevent or reverse them., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Relevant literature was identified through searches in OVID MEDLINE, OVID Embase, OVID CINAHL, and Cochrane. Additionally, Web of Science and Scopus were consulted to analyze reference lists and citations. Publications in English were included if they analyzed the occurrence of prescribing cascades. Prescribing cascades were included if at least one study demonstrated a significant association and were excluded when the adverse drug reaction could not be confirmed in the Summary of Product Characteristics. Two reviewers independently extracted and grouped similar prescribing cascades. Descriptive summaries were provided regarding dose-dependency analyses and recommendations to prevent or reverse these prescribing cascades., Results: A total of 95 publications were included, resulting in 115 prescribing cascades with confirmed adverse drug reactions for which at least one significant association was found. For 52 of these prescribing cascades, information regarding dose dependency or recommendations to prevent or reverse prescribing cascades was found. Dose dependency was analyzed and confirmed for 12 prescribing cascades. For example, antipsychotics that may cause extrapyramidal syndrome followed by anti-parkinson drugs. Recommendations focused on dosage lowering, discontinuing medication, and medication switching. Explicit recommendations regarding alternative options were given for three prescribing cascades. One example was switching to ondansetron or granisetron when extrapyramidal syndrome is experienced using metoclopramide., Conclusions: In total, 115 prescribing cascades were identified and an overview of 52 of them was generated for which recommendations to prevent or reverse them were provided. Nonetheless, information regarding alternative options for managing prescribing cascades was scarce., (© 2023. The Author(s).)

Background: Children who have been exposed in utero to maternal filarial infection are immunologically less responsive to filarial antigens, have less pathology, and are more susceptible to acquire infection than offspring of uninfected mothers. Moreover children from filaria infected mothers have been shown to be less responsive to vaccination as a consequence of an impairment of their immune response. However, it is not well known how in utero exposure to parasite antigens affects cellular immune responses., Methodology: Here, 30 pregnant women were examined for the presence of microfilaria of Loa loa and Mansonella perstans in peripheral blood. At delivery, cord blood mononuclear cells (CBMC) were obtained and the CD4+T cells were phenotyped by expression of the transcription factors Tbet, RORγt, and FOXP3., Results: No significant difference was observed between newborns from infected versus uninfected mothers in the frequencies of total CD4+T cells and CD4+T cells subsets including CD4+Tbet+, CD4+RORγt+ T and CD4+CD25hiFOXP3+ T cells. However, there was a negative association between CD4+CD25hiFOXP3+T cells and CD4+Tbet+ as well as CD4+RORγt+ T cells in the infected group only (B = -0.242, P = 0.002; B = -0.178, P = 0.013 respectively)., Conclusion: Our results suggest that filarial infection during pregnancy leads to an expansion of functionally active regulatory T cells that keep TH1 and TH17 in check.

Purpose: Nonword repetition tests (NWRT) can be useful tools together with other assessment procedures for diagnosing a developmental learning disorder in bilingual children. Concerning typically developing children, however, the link between NWRT performance and language development is still unclear. The present study contributes to this discussion by investigating the link between language-dependent NWRT performance, language development, and language exposure., Methods: A total of 20 simultaneously bilingual Russian-German children, aged 4-6 years, were tested with "The Russian language proficiency test for multilingual children (SRUK)" and "Patholinguistische Diagnostik bei Sprachentwicklungsstörungen (PDSS)" as well as language-specific nonwords for Russian and German., Results: Most children scored within the mean range in SRUK. In PDSS they scored two standard deviations below the mean range in most of the subtests. NWRT in Russian significantly correlated with the NWRT in German and also positively correlated with both comprehension and production in Russian. In contrast, the German NWRT did not correlate with comprehension or with production in German. Moreover, the correlation between the German NWRT and the comprehension of grammatical structures in Russian was significant, and the correlations between the German NWRT and the two other Russian language development tests just failed to reach significance., Conclusion: High scores in both the Russian and the German NWRT offer evidence that the ability to repeat language-specific nonwords does not differ depending on language exposure. The aim to distinguish between typical and atypical language development based on NWRT can be reached only when NWRT and all possible influencing factors in typically developed children are analyzed., (© 2023. The Author(s).)

To investigate the contributions of cognitive flexibility, inhibition and number label knowledge to children's numerical equivalence, one hundred and one 3- to 5-year-olds were administered the dimensional change card sorting task, the day-night task and the give-a-number task. The numerical equivalence was assessed with the numerical matching task in three surface similarity conditions. Results showed that, in the high surface similarity condition, cognitive flexibility and label knowledge, rather than inhibition, were significant predictors of children's performance in numerical equivalence. In the low surface similarity and the cross-mapping conditions, only cognitive flexibility, rather than number label knowledge and inhibition, significantly explained the unique variance in numerical equivalence. Besides, cognitive flexibility explained more variation in numerical equivalence in the cross-mapping condition compared with the low surface similarity condition. These findings highlight different roles of cognitive flexibility, inhibition and number label knowledge in numerical equivalence in the three surface similarity conditions., (© 2022 British Psychological Society.)

Tracheal intubation in the critically ill is associated with serious complications, mainly cardiovascular collapse and severe hypoxemia. In this narrative review, we present an update of interventions aiming to decrease these complications. MACOCHA is a simple score that helps to identify patients at risk of difficult intubation in the intensive care unit (ICU). Preoxygenation combining the use of inspiratory support and positive end-expiratory pressure should remain the standard method for preoxygenation of hypoxemic patients. Apneic oxygenation using high-flow nasal oxygen may be supplemented, to prevent further hypoxemia during tracheal intubation. Face mask ventilation after rapid sequence induction may also be used to prevent hypoxemia, in selected patients without high-risk of aspiration. Hemodynamic optimization and management are essential before, during and after the intubation procedure. All these elements can be integrated in a bundle. An airway management algorithm should be adopted in each ICU and adapted to the needs, situation and expertise of each operator. Videolaryngoscopes should be used by experienced operators., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Understanding lexico-semantic processing is crucial for dissecting the complexities of language and its disorders. Relatedness-based measures, or those which investigate the degree of relatedness in meaning between either task items or items produced by participants, offer the opportunity to harness novel computational and analytical techniques from cognitive network science. Recognizing the need to deepen our understanding of lexico-semantic deficits through diverse experimental and analytical approaches, this review explores the use of such measures in research into language disorders. A comprehensive search of four electronic databases covering publications from the last 11 years (October 2013-September 2024) identified 38 original experimental studies employing relatedness-based measures in populations with language disorders or other neurological conditions. Articles were examined for the types of tasks used, populations studied, item selection methods and analytical approaches. The predominant use of category fluency tasks emerged across studies, with a notable absence of relatedness judgement tasks or comparable paradigms. Commonly discussed populations included individuals with post-stroke aphasia, mild cognitive impairment and schizophrenia. Analytical methods varied significantly, ranging from more traditional approaches of clustering and switching to more sophisticated computational techniques. Despite the evident utility of category fluency tasks in research and clinical settings, the review underscores a critical need to diversify experimental paradigms and probe lexico-semantic processing in a more multifaceted manner. A broadened approach in future language disorder research should incorporate innovative analytical techniques, investigations of neural correlates and a wider array of tasks employing relatedness-based measures already present in healthy populations., (© 2024 The Author(s). Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Background: Due to the high prevalence of myopia, there is a growing need for the identification of myopia intervention mechanisms and targets. Metabolomics has been gradually used to investigate changes in myopia tissue metabolites over the last few years, but the potential physiological and pathological roles of amino acids and their downstream metabolites discovered by metabolomics in myopia are not fully understood., Aim of Review: Aim to explore the possible relationship between amino acid metabolism and the occurrence and development of myopia, we collected a total of 21 experimental studies related to myopia metabolomics. Perform pathway analysis using MetaboAnalyst online software. We have identified over 20 amino acids that may be associated with the development of myopia. Among them, 19 types of amino acids are common amino acids. We discussed their possible mechanisms affecting myopia and proposed future prospects for treating myopia., Key Scientific Concepts of Review: Our analysis results show that metabolomics research on myopia involves many important amino acids. We have collected literature and found that research on amino acid metabolism in myopia mainly focuses on downstream small molecule substances. Amino acids and their downstream metabolites affect the development of myopia by participating in important biochemical processes such as oxidative stress, glucose metabolism, and lipid metabolism. Enzymes, receptors, and cytokines that regulate amino acid metabolism may become potential targets for myopia treatment., Competing Interests: Declarations. Conflict of interest: The authors declare no potential conflicts of interest in the research, authorship, and publication of this article. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Electrical stimulation enhances cellular activity, promoting tissue regeneration and repair. However, specific cells and maintaining a stable energy supply are challenges for precise cell electrical stimulation therapy. Here, force-electric conversion hydrogel microspheres (Piezo@CR MPs) is devloped to induce specific stem cell aggregation and promote chondrogenic differentiation through localized electrical stimulation. These MPs contain barium titanate (BT) nanoparticles embedded in hyaluronic acid methacrylate hydrogel MPs, with a polydopamine (pDA) coating bound to stem cell recruitment peptides (CR) via π-π conjugation and electrostatic forces. Piezo@CR MPs convert pressure (ultrasound) into electrical stimulation, directing BMSCs for colonization and chondrogenesis. In vitro, directionally migrated stem cells almost covered the Piezo@CR MP surface, generating up to 451 mV of electrical output that enhanced chondrogenic differentiation. In a rabbit osteochondral defect model, Piezo@CR MPs promoted cartilage regeneration, nearly resembling native cartilage. In a rat osteoarthritis model, they reduced cartilage degeneration and improved behavioral outcomes. Additionally, Piezo@CR MPs promoted cartilage regeneration by driving the influx of extracellular calcium and activating the p38 mitogen-activated protein kinase (MAPK) pathway. In conclusion, Piezo@CR MPs offer a new approach for precise cell type electrical stimulation therapy in treating of cartilage injuries and degeneration., (© 2024 Wiley‐VCH GmbH.)

Accurate detection of tumor margins is essential for successful cancer surgery. While indocyanine green (ICG)-based near-infrared (NIR) fluorescence (FL) surgical navigation enhances the visual identification of tumor margins, its accuracy remains subjective, underscoring the need for quantitative approaches. In this study, a high spatiotemporal fluorescence lifetime (FLT) imaging technology is developed in the second near-infrared window (NIR-II, 1000-1700 nm) for quantitative tumor margin detection, utilizing folate receptor-targeted ICG nanoprobes (FPH-ICG). FPH-ICG exhibits a significantly prolonged NIR-II FLT (750 ± 7 ps vs 260 ± 3 ps) and increased NIR-II FL brightness (FPH-ICG/ICG = 3.8). In vitro and in vivo studies confirm that FPH-ICG specifically targets folate receptor-α (FRα) on SK-OV-3 ovarian cancer cells, achieving high-contrast NIR-II FL imaging with a signal-to-background ratio of 10.8. Notably, NIR-II FLT imaging demonstrates superior accuracy (90%) and consistency in defining tumor margins compared to NIR-II FL imaging (58%) in both SK-OV-3 tumor-bearing mice and clinical tumor samples. These findings underscore the potential of NIR-II FLT imaging as a quantitative tool for guiding surgical tumor margin detection., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Microtissues, engineered to emulate the complexity of human organs, are revolutionizing the fields of regenerative medicine, disease modelling, and drug screening. Despite the promise of traditional microtissue engineering, it has yet to achieve the precision required to fully replicate organ-like structures. Enter 3D bioprinting, a transformative approach that offers unparalleled control over the microtissue's spatial arrangement and mechanical properties. This cutting-edge technology enables the detailed layering of bioinks, crafting microtissues with tissue-like 3D structures. It allows for the direct construction of organoids and the fine-tuning of the mechanical forces vital for tissue maturation. Moreover, 3D-printed devices provide microtissues with the necessary guidance and microenvironments, facilitating sophisticated tissue interactions. The applications of 3D-printed microtissues are expanding rapidly, with successful demonstrations of their functionality in vitro and in vivo. This technology excels at replicating the intricate processes of tissue development, offering a more ethical and controlled alternative to traditional animal models. By simulating in vivo conditions, 3D-printed microtissues are emerging as powerful tools for personalized drug screening, offering new avenues for pharmaceutical development and precision medicine., (© 2024 Wiley‐VCH GmbH.)

In recent years, impairing mitochondria in cancer cells gained attention as alternative cancer therapy. In this context, non-steroidal anti-inflammatory (NSAID) drugs are interesting candidates to damage mitochondria in cancer cells. However, routing NSAIDs specifically into the mitochondria remained a major challenge and less explored. Herein, we have synthesized a small library of Meclofenamic acid and Naproxen derivatives having ester and amide linkage with substituted triphenylphosphonium cations for mitochondria targeting. Screening in cervical cancer (HeLa), breast cancer (MCF7) and colon cancer (HCT-116) cells revealed a Meclofenamic acid derivative having ester linkage with tri (4-methoxyphenyl) phosphonium cation (8A3) which induced mitochondrial damage through mitochondrial outer membrane permeabilization (MOMP) followed by generation of reactive oxygen species (ROS) in the HCT-116 cells. This 8A3-mediated mitochondrial impairment triggered apoptosis by inhibiting Cox-2, reduction in Bcl-2/Bcl-xl expression and Caspase-3/9 cleavage leading to remarkable HCT-116 cell death. This novel mitochondrion targeted Meclofenamic acid derivative has the potential to be used as a chemical biology tool to understand the role of NSAIDs in mitochondria towards cancer therapy., (© 2024 Wiley-VCH GmbH.)

Suspoemulsions are used for food, cosmetic and pharmaceutical products, including food such as dairy products and non-dairy alternatives. Product properties, such as flow behavior or sensory perception of non-dairy products differ from those of dairy products and are therefore perceived by consumers as products of inferior quality. One reason for this may be the crystallization behavior of the added triglycerides leading to differences in solid fat content in comparison to cow milk. This is discussed with the solidity of the dispersed phase as a parameter of suspoemulsions. The solidity was varied by using low and high melting triglycerides and measuring at different temperatures. The dispersed phase fraction is φ = 30%. The droplet size distribution showed a x 50,3 of 1.2 and 3.66 μm, mimicking the droplet sizes of milk and dairy cream. Rheological frequency sweeps were carried out within a temperature range from 5°C to 50°C. The differences in solidity of the dispersed phase caused no changes in viscosity at each temperature. In contrast, oral tribology distinguished different solidities of the dispersed phase with changes in the friction coefficient. The friction coefficient was determined for increasing rotational speeds (0.01-100 mm/s), to compare the so called Stribeck curves with each other. In general, with increasing solidity of the dispersed phase, the friction coefficient increases. Comparing the Stribeck curves of pure butter fat suspoemulsion with those of plant-based fat suspoemulsions, different plant-based fats can be mixed, to mimic the friction profile of milk products in plant-based alternatives., (© 2024 The Author(s). Journal of Texture Studies published by Wiley Periodicals LLC.)

Purpose: Normative ADC values of the pineal gland in young children are currently lacking, however, these are potentially useful in the differential diagnosis of pineal involvement in trilateral retinoblastoma, which is challenging when the size of the tumor is less than 10-15 mm. The main objective of this study was to establish ADC reference values of the normal pineal gland in a large cohort of children between 0 and 4 years., Methods: This retrospective study was conducted in a tertiary pediatric hospital. We collected 64 patients with normal MRI examination (between 2017 and 2024) and clinical indication unrelated to the pineal gland, and divided them into 5 age groups (0 to 4 years). Gland size and mean ADC values were calculated, using the ellipsoid formula and ROI/histogram analysis, respectively. The established values were tested in three cases of trilateral retinoblastoma (10 to 20 months)., Results: Mean ADC values were always above 1000 × 10 - 6 mm 2 /s, while in patients with trilateral retinoblastoma they were around 800 × 10 - 6 mm 2 /s. Pineal ADC values were identical in both genders. The volume of the pineal gland showed a tendency to increase with age., Conclusions: We present ADC reference data for the pineal gland in children under 4 years of age. The distribution of mean ADC values of trilateral retinoblastoma was significantly different from the normative values, hence, the use DWI/ADC may help to identify small trilateral retinoblastoma in children with ocular pathology., Competing Interests: Declarations. Ethical approval: All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional research committee (Clinical Research Adoption Committee) and with the 1964 Helsinki Declaration and its later amendments. Informed consent: Standard clinical informed consent was obtained at the time of the scan. Informed consent for this specific study was not applicable given the retrospective nature of this research. This study does not contain any personal information that could lead to the identification of the patients. All the images used are anonymized and do not allow the individuals to be identified. Conflict of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Measurement-based care (MBC), the use of routine assessment to guide clinical decision-making, has the potential to significantly enhance the quality of mental health services for youth by improving the detection and prevention of harm. Concerns exist, however, that widespread efforts to implement MBC may have a negative impact on youth mental health care. We explore both perspectives by describing how MBC can be leveraged as a tool to detect and prevent harmful treatment in youth and how misapplication of MBC also has the potential to cause harm. This discussion focuses on how MBC can help therapists identify harm caused by ineffective practices (i.e., deterioration or no symptoms changes), poor client engagement (e.g., early drop-out, poor alliance), and adverse events (e.g., injury caused by treatment). We also discuss multi-level applications of aggregated MBC data to prevent harm through workforce development and organizational and health systems quality and cost of care improvement initiatives. Misapplication of MBC by failing to adhere to MBC best practices, overreliance on data above clinical judgement, providing insufficient organizational support, and using MBC data to justify cost containment are all discussed as possible sources of harm. We conclude with a discussion of future directions for research needed to advance the application of MBC to the prevention of harm in youth psychotherapy., Competing Interests: Compliance with Ethical Standard. Competing Interests: Vanderbilt University and Susan Douglas receive compensation related to the Peabody Treatment Progress Battery; and Susan Douglas has a financial relationship with MIRAH, and both are Measurement-Based Care (MBC) tools. The author declares a potential conflict of interest. There is a management plan in place at Vanderbilt University to monitor that this potential conflict does not jeopardize the objectivity of Dr. Douglas’ research. Elizabeth Casline, Maartje van Sonsbeek, Kelsie Okamura, and Amanda Jensen-Doss have no conflicts of interest to report., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: High-flow nasal oxygenation has been shown to improve oxygenation during induction of anaesthesia in parturients who are not obese. However, data on the efficacy of high-flow nasal oxygen in parturients living with obesity are lacking. This study investigated the effects of high-flow nasal oxygenation on pre-oxygenation and apnoea oxygenation during tracheal intubation in parturients living with obesity., Methods: This prospective, randomised clinical trial was conducted at two tertiary hospitals and included parturients with BMI > 30 kg.m -2 undergoing scheduled caesarean delivery under general anaesthesia. Parturients were allocated randomly to standard facemask or high-flow nasal oxygen groups (oxygen flow rates 10 l.min -1 and 50 l.min -1 , respectively). The primary outcome measure was arterial partial pressure of oxygen after 3 min of pre-oxygenation., Results: 54 patients completed the study. The arterial partial pressure of oxygen after 3 min of pre-oxygenation was significantly lower in parturients allocated to the standard facemask group compared with those allocated to the high-flow nasal oxygen group (mean (SD) 40.1 (8.9) kPa vs. 53.8 (9.7) kPa, p < 0.001). End-tidal oxygen concentration on commencing ventilation was also lower in parturients allocated to the standard facemask group compared with those allocated to the high flow-nasal oxygen group (mean (SD) 78.3 (5.38)% vs. 86.2 (5.10)%, p < 0.001). The arterial partial pressure of carbon dioxide post tracheal intubation and fetal outcomes were similar in both groups., Discussion: Pre-oxygenation using high-flow nasal oxygenation provided a higher arterial partial pressure of oxygen and end-tidal oxygen concentration during general anaesthesia induction than standard facemask oxygenation in parturients living with obesity; however, the differences were not clinically meaningful. High-flow nasal oxygenation may be considered as an alternative option for pre-oxygenation during rapid sequence induction in parturients living with obesity., (© 2024 Association of Anaesthetists.)

Purpose: To employ a validated survey for evaluation of quality of life (QoL) outcomes and associated factors in a US cohort of adult patients with acquired anophthalmia wearing a prosthesis., Methods: A retrospective cohort study was performed at a single, US academic institution of patients cared for between 2012 and 2021. The electronic medical record database was queried for adult patients with a history of evisceration or enucleation surgery and placement of an orbital implant. Identified patients were asked to anonymously complete a validated QoL questionnaire from which the Global Ocular Prosthesis Score was assessed. Summary statistics were reported, and analysis of variance was used to determine surgical and demographic factors associated with QoL survey scores., Results: A total of 81 patients completed the questionnaire. Mean age was 45.8 years (range: 18-96 years), and 54.3% of patients identified as women. Enucleation was performed in 81.4% of eyes (n = 66), while the remaining 17.3% underwent evisceration (n = 14). The mean and median Global Ocular Prosthesis Score (out of 100) were 67.51 and 68.00, respectively. Multivariate analysis demonstrated the etiologies of glaucoma (95% confidence interval: 0.84-25.40, p = 0.04) and endophthalmitis (95% confidence interval: 0.41-23.72, p = 0.04) to be significantly associated with higher total Global Ocular Prosthesis Score. Several other factors including employment status, etiology of anophthalmia, gender, and level of education were also significantly associated with subdomain scores (p < 0.05)., Conclusions: Among patients with anophthalmia wearing an ocular prosthesis, the etiology of anophthalmia was significantly associated with the Global Ocular Prosthesis Score. Employment status, etiology of anophthalmia, gender, and level of education were also observed to have statistically significant associations with subdomain scores. Knowledge of these factors moving forward may help the surgeon manage expectations, mitigate challenges, and promote higher QoL outcomes for patients with acquired anophthalmia., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Peptide receptor radionuclide therapy (PRRT) using [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-DOTATATE) represents an established treatment modality for somatostatin receptor-positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2. The studies have demonstrated that four cycles of PRRT with 177 Lu-DOTATATE prolongs progression-free survival and preserves quality of life, in patients with grade 1 and 2 advanced GEP NET. Notably, first-line PRRT using 177 Lu-DOTATATE in grade 2 and 3 GEP NET patients has also shown efficacy and safety. Furthermore, PRRT can ameliorate symptoms in patients with NET-associated functioning syndromes. Although various studies have explored alternative radionuclides for PRRT, none currently meet the criteria for routine clinical implementation. Ongoing research aims to further enhance PRRT, and the results from large clinical trials comparing PRRT with other NET treatments are anticipated, potentially leading to significant modifications in NET treatment strategies and PRRT protocols. The results of these studies are likely to help address existing knowledge gaps in the coming years. This review describes the clinical practice, recent developments and future treatment options of PRRT in patients with grade 1 and 2 GEP NET., (© 2024 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Habitat loss can lead to biotic homogenization (decrease in β diversity) or differentiation (increase in β diversity) of biological communities. However, it is unclear which of these ecological processes predominates in human-modified landscapes. We used data on vertebrates, invertebrates, and plants to quantify β diversity based on species occurrence and abundance among communities in 1367 landscapes with varying amounts of habitat (<30%, 30-60%, or >60% of forest cover) throughout the Brazilian Atlantic Forest. Decreases in habitat amount below 30% led to increased compositional similarity of vertebrate and invertebrate communities, which may indicate a process of biotic homogenization throughout the Brazilian Atlantic Forest. No pattern was detected in plant communities. We found that habitat loss was associated with a deterministic increase in faunal community similarity, which is consistent with a selected subset of species being capable of thriving in human-modified landscapes. The lack of pattern found in plants was consistent with known variation between taxa in community responses to habitat amount. Brazilian legislation requiring the preservation of 20% of Atlantic Forest native vegetation may be insufficient to prevent the biotic homogenization of faunal communities. Our results highlight the importance of preserving large amounts of habitat, providing source areas for the recolonization of deforested landscapes, and avoiding large-scale impacts of homogenization of the Brazilian Atlantic Forest., (© 2024 Society for Conservation Biology.)

Magnetic resonance imaging (MRI) is a noninvasive and radiation-free technique used for soft tissue. However, there are some limitations of the MRI modality, such as low sensitivity and poor image resolution. Artificially engineered magnetic nanoprobes have been extensively explored as a versatile platform for ultrasensitive MRI contrast agents due to their unique physiochemical characteristics and tunable magnetic properties. In this review, the emphasis is on recent progress in MRI nanoprobes with different structures and elements, including gadolinium-, iron-, manganese-based and metal-free nanoprobes. The key influencing factors and advanced engineering strategies for modulating the relaxation ratio of MRI nanoprobes are systematically condensed. Furthermore, the widespread and noninvasive visualization applications of MRI nanoprobes for real time monitoring of major organs and accurate disease diagnosing, such as cerebrovascular, ischemia, Alzheimer's disease, liver fibrosis, whole-body tumors, inflammation, as well as multi-mode imaging applications are summarized. Finally, the challenges and prospects for the future development of MRI nanoprobes are discussed, and promising strategies are specifically emphasized for improving biocompatibility, precisely engineering of optimal size, AI-driven prediction and design, and multifunctional self-assembly to enhance diagnostics. This review will provide new inspiration for artificial engineering and nanotechnology-based molecular probes for medical diagnosis and therapy with ultrasensitive MRI., (© 2024 Wiley‐VCH GmbH.)

The Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus and a class 1 carcinogen that is closely associated with a series of malignant lymphomas and epithelial cell carcinomas. Although these EBV-related cancers may exhibit different features in clinical symptoms and anatomical sites, they all have a characteristic immune-suppressed tumor immune microenvironment (TIME) that is tightly correlated with an abundance of tumor-infiltrating lymphocytes (TILs) that primarily result from the EBV infection. Overwhelming evidence indicates that an upregulation of immune-checkpoint molecules is a powerful strategy employed by the EBV to escape immune surveillance. While previous studies have mainly focused on the therapeutic effects of PD-1 and CTLA-4 blockades in treating EBV-associated tumors, several novel inhibitory receptors (e.g., CD47, LAG-3, TIM-3, VISTA, and DDR1) have recently been identified as potential targets for treating EBV-associated malignancies (EBVaMs). This review retrospectively summarizes the biological mechanisms used for immune checkpoint evasion in EBV-associated tumors. Its purpose is to update our current knowledge concerning the underlying mechanisms by which an immune checkpoint blockade triggers host antitumor immunity against EBVaMs. Additionally, this review may help investigators to more fully understand the correlation between EBV infection and tumor development and subsequently develop novel therapeutic strategies., (© 2024 Federation of American Societies for Experimental Biology.)

Purpose: 177 Lu-OncoFAP-23 is a novel FAP-targeted radioligand therapeutic (RLT) with high and prolonged tumor residence time and promising preclinical efficacy. In this work, we investigated the correlation between the injected molar dose and the in vivo tumor-to-organ ratios and tumor-targeting performance of 177 Lu-OncoFAP-23., Methods: We evaluated the quantitative biodistribution profile of 177 Lu-OncoFAP-23 at different molar doses (i.e., 3 to 2250 nmol/kg) in tumor-bearing mice by means of ex vivo gamma counting, we included 177 Lu-OncoFAP and 177 Lu-BiOncoFAP as experimental controls., Results: The biodistribution profile of 177 Lu-OncoFAP-23 strongly depends on the molar dose injected. Molar doses below 30 nmol/kg result in unwanted uptake of the compound in healthy organs, while doses higher than 725 nmol/kg determined a reduced tumor uptake due to receptor saturation. We identified an optimal molar dose ranging from 90 to 250 nmol/kg, characterized by elevated tumor uptake and adequate tumor-to-organ ratios., Conclusion: 177 Lu-OncoFAP-23 presents a favorable in vivo biodistribution profile at molar doses ranging from 90 to 250 nmol/kg in tumor-bearing mice. Our results guide the design of the first-in-human Phase I clinical trial with this novel FAP-targeted radioligand therapeutic., Competing Interests: Declarations Competing interests DN is co-founder, CEO, CSO, and President of the Scientific Advisory Board of Philogen. AG, MB and SC are employed by Philochem AG, the research and development unit of the Philogen group., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Zebrafish (Danio rerio), an alternative to rodents, are widely used in neurological, genetic, and toxicology research. The zebrafish larval spinal cord injury model has been used in neural mechanistic analyses owing to its high regenerative capacity and throughput; however, it also had several limitations in imitating rodents. Therefore, we investigated the use of adult zebrafish as an alternative model to rodents for evaluating nerve regeneration. Here, we established a novel spinal cord regeneration evaluation method, which was based on the maximum swimming speed of adult zebrafish in a custom-built hydrodynamic-based aquarium. The spinal cords of adult male zebrafish were crushed using forceps, and maximum swimming speed and histological spinal cord regeneration were evaluated. Spinal cord-injured zebrafish showed a significant decline in motor function, followed by recovery at 3 weeks postoperatively, accompanied by histological regeneration. Spinal cord regeneration can be indirectly assessed by monitoring maximum swimming speed. They were also fed a diet containing fig extract, which can promote peripheral nerve regeneration; they were fed daily starting 1 week before the operation. Maximum swimming speed was measured time-dependently until 3 weeks postoperatively. Fig-consuming fish showed improved recovery of maximum swimming speed compared to the controls, which was consistent with the histological analysis. In summary, we established a spinal cord regeneration assessment system using adult zebrafish in a customized aquarium, which enables researchers to evaluate spinal cord regeneration in adult zebrafish similar to that of rodent experiments, contributing to faster and easier screening of neuroregenerative technology., Competing Interests: Declarations Conflict of interest HM, SS, YH, TH, SM, NO, and YM are employed by Kao Corporation. This work was financially supported by the Kao Corporation. HM, SS, TH, SM, and YM are listed as inventors on patent application JP2022/028434, submitted by Kao Corporation, which covers this evaluation system and the effectiveness of figs. Ethical approval All experiments were conducted in accordance with the Animal Care and Experimentation Facility Committee of Kao Corporation. Employment HM, SS, YH, TH, SM, NO, and YM are employed by Kao Corporation., (© 2024. The Author(s).)

1,2-Diamination of alkenes represents an attractive way to generate differentiated vicinal diamines, which are prevalent motifs in biologically active compounds and catalysts. However, existing methods are usually limited in scope and produce diamines where one or both nitrogens are protected, adding synthetic steps for deprotection and further N-functionalization to reach a desired target. Furthermore, the range of amino groups that can be introduced at the internal position is fairly limited. Here we describe a 1,2-diamination of styrenes that directly installs a free amino group at the terminal position and a wide variety of unprotected nitrogen nucleophiles (primary or secondary alkyl or aromatic amines, sulfoximines, N-heterocycles, and ammonia surrogate) at the internal position. Two complementary sets of conditions encompass electronically activated and deactivated styrenes with diverse substitution patterns and functional groups. Moreover, this strategy can be extended to the 1,2-aminothiolation of styrenes., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Aim: This qualitative study explored the lived experiences of the patients with microphthalmia and anophthalmia and their parents, focusing on the healthcare, school settings and daily life challenges to improve patient management., Methods: In-depth interviews were conducted in Stockholm, Sweden, from October 2022 to June 2023. Participants were recruited through the St Erik Eye Hospital database (2008-2022), and the data was analysed using reflexive thematic analysis., Results: The study included 15 patients (9 female and 6 male), with a median age of 21 years (range 15-31), and 1 parent per patient. Five key themes were identified from the parental interviews and three from the patient interviews. Both groups emphasised the need for improvements in healthcare, including better physician continuity, emotional support, information provision and prosthesis functionality. Families of those with severe bilateral visual impairment highlighted the need for additional school and daily life support. While some parents had future concerns, most patients viewed their condition as a natural part of life., Conclusion: Patients and parents shared insights on the psychosocial impact and suggested improvements in the healthcare and school settings, providing valuable guidance for enhancing care and management for this patient group., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Purpose: Educational impact is dependent on student engagement. Assessment design can provide a scaffold for student engagement to determine the focus of student efforts. Little is known about how medical students engage with assessment. Therefore, we asked the following research question: How do medical students engage with the process of assessment and their assessment data in 2 clinical assessment systems?, Method: This multi-institutional, cross-sectional constructivist grounded theory study of fourth-year undergraduate medical students at the University of Washington and Cleveland Clinic Lerner College of Medicine assessed 2 different assessment systems: traditional tiered grading, in which clerkship grades were summative, and programmatic assessment, in which students received low-stake, narrative feedback across clerkships with progress based on aggregated performance data in student portfolios. All fourth-year students were invited to participate in one-on-one semistructured interviews guided by student engagement theory between September 2022 and January 2023. Verbatim transcripts underwent iterative, qualitative analysis., Results: Twenty-two medical students were interviewed, 13 from a traditional grading assessment system and 9 from a programmatic assessment system. Three major ways in which assessment systems affected how students engaged with their assessments were categorized into the affective, cognitive, and behavioral domains of engagement: as a sociocultural statement of value, as the cognitive load associated with the assessment system and practices themselves, and as the locus of power and control in learning and authentic practice., Conclusions: Medical students' beliefs about assessment goals, cognitive burden of assessment, and relationships with others significantly affected their engagement with their assessments. In assessment systems that reward grading and an archetypal way of being, students report engaging by prioritizing image over learning. In programmatic assessment systems, students describe more fully and authentically engaging in their assessment for and as learning. Systems of assessment communicate what is rewarded, and you get what you reward., (Copyright © 2024 the Association of American Medical Colleges.)

Anti-synthetase syndrome (AS) is a subset of idiopathic inflammatory myopathy (IIM) characterized by the presence of anti-aminoacyl-transfer RNA synthetase accompanied by myositis, interstitial lung disease and other clinical features. According to a recent multicentric study, 31% of AS patients present skin lesions compatible with dermatomyositis, but sclerodermiform features are rare. Therefore, we aimed to report the case of a patient with simultaneous diagnosis of AS, deep morphea, vasculitic neuropathy, and myelodysplastic syndrome and review the current literature regarding these uncommon associations. A 57 year old man with axial and symmetrical proximal muscle weakness, skin thickening and B symptoms, later diagnosed with PL7 + AS, deep morphea, myelodysplastic syndrome (MDS) and vasculitic neuropathy documented by histopathologic studies and immunologic assessments. Since both AS and deep morphea share the vasculopathic changes and type II interferon-induced inflammation, we hypothesize that they may share pathogenic mechanisms. The muscle biopsy of the patient was consistent with AS and showed focal neutrophil infiltration. The patient received intensive immunosuppressive therapy for AS and vasculitic neuropathy, with high dose steroids, intravenous immunoglobulin (IVIg) and rituximab. Nonetheless, he suffered an unfavorable evolution with a fatal outcome due to septic shock. Albeit sclerodermiform features are rare in patients with AS, we propose a pathogenic link among AS, deep morphea and the autoimmune/autoinflammatory signs of MDS. The vasculopathic changes along with the activation of the innate and adaptive immune system leading to the production of proinflammatory cytokines may have been one of the contributing factors for the coexisting diagnosis of the patient., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fish ear bones, known as otoliths, are often collected in fisheries to assist in management, and are a common sample type in museum and national archives. Beyond their utility for ageing, morphological and trace element analysis, otoliths are a repository of valuable genomic information. Previous work has shown that DNA can be extracted from the trace quantities of tissue remaining on the surface of otoliths, despite the fact that they are often stored dry at room temperature. However, much of this work has used reduced representation sequencing methods in clean lab conditions, to achieve adequate yields of DNA, libraries and ultimately single-nucleotide polymorphisms (SNPs). Here, we pioneer the use of small-scale (spike-in) sequencing to screen contemporary otolith samples prepared in regular molecular biology (in contrast to clean) laboratories for contamination and quality levels, submitting for whole-genome resequencing only samples above a defined endogenous DNA threshold. Despite the typically low quality and quantity of DNA extracted from otoliths, we are able to produce whole-genome libraries and ultimately sets of filtered, unlinked and even putatively adaptive SNPs of ample numbers for downstream uses in population, climate and conservation genomics. By comparing with a set of tissue samples from the same species, we are able to highlight the quality and efficacy of otolith samples from DNA extraction and library preparation, to bioinformatic preprocessing and SNP calling. We provide detailed schematics, protocols and scripts of our approach, such that it can be adopted widely by the community, improving the use of otoliths as a source of valuable genomic data., (© 2024 The Author(s). Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Background: Mechanical ventilation is a core intervention in critical care, but may also lead to negative consequences. Therefore, ventilator weaning is crucial for patient recovery. Numerous weaning interventions have been investigated, but an overview of interventions to evaluate different foci on weaning research is still missing., Aim: To provide an overview of interventions associated with ventilator weaning., Study Design: We conducted a scoping review. A systematic search of the Medline, CINAHL and Cochrane Library databases was carried out in May 2023. Interventions from studies or reviews that aimed to extubate or decannulate mechanically ventilated patients in intensive care units were included. Studies concerning children, outpatients or non-invasive ventilation were excluded. Screening and data extraction were conducted independently by three reviewers. Identified interventions were thematically analysed and clustered., Results: Of the 7175 records identified, 193 studies were included. A total of six clusters were formed: entitled enteral nutrition (three studies), tracheostomy (17 studies), physical treatment (13 studies), ventilation modes and settings (47 studies), intervention bundles (42 studies), and pharmacological interventions including analgesic agents (8 studies), sedative agents (53 studies) and other agents (15 studies)., Conclusions: Ventilator weaning is widely researched with a special focus on ventilation modes and pharmacological agents. Some aspects remain poorly researched or unaddressed (e.g. nutrition, delirium treatment, sleep promotion)., Relevance to Clinical Practice: This review compiles studies on ventilator weaning interventions in thematic clusters, highlighting the need for multidisciplinary care and consideration of various interventions. Future research should combine different interventions and investigate their interconnection., (© 2024 The Author(s). Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

Age-related macular degeneration (AMD) is an emerging cause of blindness in aged people worldwide. One of the key signs of AMD is the degeneration of the retinal pigment epithelium (RPE), which is indispensable for the maintenance of the adjacent photoreceptors. Because of impaired energy metabolism resulting from constant light exposure, hypoxia, and oxidative stress, accumulation of drusen in AMD-affected eyes is observed. Drusen contain damaged cellular proteins, lipoprotein particles, lipids and carbohydrates and they are related to impaired protein clearance, inflammation, and extracellular matrix modification. When autophagy, a major cellular proteostasis pathway, is impaired, the accumulations of intracellular lipofuscin and extracellular drusen are detected. As these aggregates grow over time, they finally cause the disorganisation and destruction of the RPE and photoreceptors leading to visual loss. In this review, the role of autophagy in drusen biogenesis is discussed since impairment in removing cellular waste in RPE cells plays a key role in AMD progression. In the future, means which improve intracellular clearance might be of use in AMD therapy to slow the progression of drusen formation., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Introduction: Patients requiring emergent endotracheal intubation are at higher risk of post-intubation hypotension due to altered physiology in critical illness. Post-intubation hypotension increases mortality and hospital length of stay, however, the impact of vasopressors on its incidence and outcomes is not known. This scoping review identified studies reporting hemodynamic data in patients undergoing emergent intubation to provide a literature overview on post-intubation hypotension in cohorts that did and did not receive vasopressors., Methods: A systematic search of CINAHL, Cochrane, EMBASE and PubMed-Medline was performed from database inception until September 28, 2023. Two independent reviewers completed the title and abstract screen, full text review and data extraction per PRISMA guidelines. Studies including patients < 18 years or intubations during cardiac arrest were excluded. Primary outcome was the presence of hypotension within 30 min of emergent intubation. Secondary outcomes included mortality at 1 h and in-hospital., Results: The systematic search yielded 13,126 articles, with 61 selected for final inclusion. There were 24,547 patients with a mean age of 57.2 years and a slight male predominance (63.8%). Respiratory failure was the most common intubation indication. Across 18 studies reporting on vasopressor use prior to intubation, 1171/7085 patients received vasopressors pre-intubation. Post-intubation hypotension occurred in 22.2% of patients across all studies, and in 34.3% of patients in studies where vasopressor administration pre-intubation was specifically reported. One-hour mortality of patients across all studies and within the vasopressor use studies was 1.2% and 1.6%, respectively. In-hospital mortality across studies was 21.5%, and 13.1% in studies which reported on vasopressor use pre-intubation., Conclusion: Patients requiring emergent intubation have a high rate of post-intubation hypotension and in-hospital mortality. While there is an intuitive rationale for the use of vasopressors during emergent intubation, current evidence is limited to support a definitive change in clinical practice at this time., Competing Interests: Declarations Conflict of interest PM has been a junior instructor for AIME and The RESUS course but has not received honoraria for these. JG has received honoraria as an instructor for AIME and The RESUS course. OL is Co-Chair for Sepsis Canada; however, this is not a paid position. The remaining authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to the Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Atherosclerosis is an age-related pathological process associated with elevated levels of legumain in plaques and plasma. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the role of legumain in the progression of atherosclerotic plaques, with a particular focus on functional and phenotypic changes in CD4 + T cells. Apolipoprotein E-deficient (Apoe -/- ) mice were crossed with legumain-deficient (Lgmn -/- ) mice to generate Lgmn -/- Apoe -/- mice. CD4 + T cells accumulated in the atherosclerotic plaques of Apoe -/- mice fed a high-fat diet. Deletion of legumain attenuated the deposition of CD4 + T cells in plaques and reduced the number of atherosclerotic lesions. The levels of CD4 + T cells in the blood, lymph nodes, and spleen were decreased in Lgmn -/- mice. Transcriptomic analysis revealed that the deletion of legumain decreased the differentiation, survival, and function of CD4 + memory T cells by suppressing the T cell receptor (TCR) signaling pathway. These changes are accompanied by the downregulation of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and the reduced release of interleukin (IL)-2 and interferon (IFN)-γ. These results suggest that legumain deficiency may play a role in the development of atherosclerosis by impairing the survival, proliferation, and function of CD4 + T cells. Inhibition of legumain activity may be an innovative therapy for the treatment of atherosclerosis., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Introduction: Routine outcome monitoring (ROM) and feedback is an evidence-supported strategy for evaluating alcohol and other drug (AOD) treatment outcomes. However, the implementation of ROM and feedback into AOD services remains a significant challenge. Research aimed at understanding client perspectives on ROM and feedback is needed to facilitate successful implementation. This study examined experiences with and perceptions of ROM and feedback in a sample of clients receiving AOD treatment., Methods: Interviews and online surveys were conducted with N = 26 people (13 male; M age  = 36.12 years, SD = 10.29) enrolled in an AOD treatment program in Australia. Data analysis of the transcripts was guided by thematic analysis, while descriptive statistics were used to analyse quantitative survey data., Results: Four major themes were identified in the qualitative data: (i) ROM and feedback is valuable to AOD treatment; (ii) clear and concise outcome measures with an integrated feedback loop are vital to reliable ROM; (iii) desire for visual and verbal feedback that highlights progress; and (iv) ROM and feedback can be emotionally challenging., Discussion and Conclusions: Participants valued ROM when it was clearly integrated within AOD treatment and they received feedback on their responses. Potential facilitators to implementing and improving the provision of ROM and feedback in AOD treatment include: (i) a clear, treatment-based rationale to foster client buy-in for ROM and maximise AOD treatment benefit; (ii) brief outcome measure surveys; and (iii) graphical visualisations of ROM feedback., (© 2024 Australasian Professional Society on Alcohol and other Drugs.)

Objective: Although parenting programs are the most widely used approach to reduce disruptive behavior in children, there is a notable lack of understanding of the exact changes in parenting that underlie their effects. Challenges include the frequent use of composite measures of parenting behavior and insufficient power to detect mediation effects and individual differences in these in individual trials., Method: Individual participant data from 14 European randomized controlled trials of social learning-based parenting programs were pooled to examine which specific parenting behaviors best explain program effects. Participants included 3,252 families with children ages 1 to 13 years. Parental use of praise, tangible rewards, physical discipline, harsh verbal discipline, and not following through on discipline were included as putative mediators. Additionally, the study explored whether subgroups of families showing different mediational pathways exist., Results: Changes in parenting partially mediated program effects, with all included parenting behaviors except parental use of praise serving as unique mediators. Less harsh verbal discipline and increased following through on discipline were the strongest mediators. The study identified 3 subgroups with distinct responses to parenting programs. Most families benefited, partly through increased following through on discipline; families with the least or most difficulties were more likely to benefit less or not at all., Conclusion: These findings offer insight into the specific parenting behavior changes key to reducing disruptive child behavior, while highlighting the need for innovative research methodologies to gain a deeper understanding of individual differences in parenting program benefits and mechanisms., Study Preregistration Information: Study Preregistration: Individual Participant Data Meta-analysis: Individual Differences in Mediators of Parenting Program Effects on Disruptive Behavior; https://doi.org/10.1016/j.jaac.2023.11.005., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The therapeutic relationship plays a crucial role in nursing care for people with mental illness. Adopting a systemic and person-centred approach that considers the individual experiences and needs of the person is paramount. However, no instruments were found in the literature designed to evaluate the nurse-patient therapeutic relationship from the perspective of a person with mental illness. This study aimed to develop and evaluate the psychometric properties of an instrument for assessing the quality of the nurse-patient therapeutic relationship from the patient's perspective. An e-Delphi study was conducted to develop the assessment tool, and a psychometric study was carried out to examine its psychometric properties. The sample comprised 240 adults with mental illness. Internal consistency was assessed using Cronbach's alpha and the Omega coefficient. The final structure of the assessment instrument included 24 items distributed across two factors, explaining 64.2% of the variance. Cronbach's alpha was 0.94, and the Omega coefficient was 0.96. The intraclass correlation coefficient was 0.84 (95% CI: 0.66-0.92). The therapeutic relationship assessment scale (TRAS-Patient) shows good psychometric properties. This is a relevant tool for assessing the quality of the nurse-patient therapeutic relationship from the patient's perspective, thus promoting a patient-centred approach and responding to the patient's needs. Mental health nurses can access a tool for evaluating the nurse-patient therapeutic relationship centred on disciplinary knowledge. This enables patient involvement in care, enhanced care and person-centred practice., (© 2024 The Author(s). International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

The genetic analysis of potato is hampered by the complexity of tetrasomic inheritance. An ongoing effort aims to transform the clonally propagated tetraploid potato into a seed-propagated diploid crop, which would make genetic analyses much easier owing to disomic inheritance. Here, we construct and report the large-scale genetic and heterotic characteristics of a diploid F 2 potato population derived from the cross of two highly homozygous inbred lines. We investigate 20,382 traits generated from multi-omics dataset and identify 25,770 quantitative trait loci (QTLs). Coupled with gene expression data, we construct a systems-genetics network for gene discovery in potatoes. Importantly, we explore the genetic basis of heterosis in this population, especially for yield and male fertility heterosis. We find that positive heterotic effects of yield-related QTLs and negative heterotic effects of metabolite QTLs (mQTLs) contribute to yield heterosis. Additionally, we identify a PME gene with a dominance heterotic effect that plays an important role in male fertility heterosis. This study provides genetic resources for the potato community and will facilitate the application of heterosis in diploid potato breeding., (© 2024. The Author(s).)

Background: Glycoprotein (GP)VI is a platelet-specific collagen receptor required for platelet activation during hemostasis. Platelet reactivity toward collagen is routinely assessed during diagnostic workup of platelet disorders. GPVI can be activated by inducing receptor clustering with suspensions of fibrillar collagen or synthetic cross-linked collagen-related peptide (CRP-XL). However, these suspensions are poorly standardized or difficult to produce. Nanobodies are small recombinant camelid-derived heavy-chain antibody variable regions. They are highly stable, specific, and ideal candidates for developing a stable GPVI agonist for diagnostic assays., Objectives: Develop a stable nanobody-based GPVI agonist., Methods: Nanobody D2 (NbD2) was produced as dimers and purified. Tetramers were generated via C-terminal fusion of dimers with click chemistry. Nanobody constructs were functionally characterized with light transmission aggregometry (LTA) in platelet-rich plasma and whole blood flow cytometry. Diagnostic performance was assessed in patients with inherited platelet function disorders with LTA and flow cytometry., Results: NbD2 was specific for human platelet GPVI. Dimers did not result in platelet activation in LTA or flow cytometry settings and fully inhibited CRP-XL-induced P-selectin expression and fibrinogen binding in whole blood and attenuated collagen-induced platelet aggregation in platelet-rich plasma. However, NbD2 tetramers caused full platelet aggregation, as well as P-selectin expression and fibrinogen binding. NbD2 tetramers were able to discriminate between inherited platelet function disorder patients and healthy controls based on fibrinogen binding, similar to CRP-XL., Conclusion: Nanobody tetramers to GPVI induce platelet activation and can be used to assess the GPVI pathway in diagnostic assays., (© 2024 The Author(s).)

Background: The surgical decision for limb-salvage with free tissue transfer (FTT), partial foot amputation (PFA), or below-knee amputation (BKA) for complex lower extremity (LE) wounds hinges on several factors, including patient choice and baseline function. However, patient-reported outcome measures (PROMs) on LE function, pain, and QoL for chronic LE wound interventions are limited. Thus, the study aim was to compare PROMs in patients who underwent FTT, PFA, or BKA for chronic LE wounds., Methods: PROMs were collected via QR code for all adult chronic LE wound patients who presented to a tertiary wound center between June 2022 and June 2023. A cross-sectional analysis of patients who underwent FTT, PFA, or BKA was conducted. The 12-Item Short Survey (SF-12), PROM Information System Pain Intensity (PROMIS-3a), and Lower Extremity Functional Scale (LEFS) were completed at 1, 3, and 6 months and 1, 3, and 5 years postoperatively. Patient demographics, comorbidities, preoperative characteristics, and amputation details were collected., Results: Of 200 survey sets, 71 (35.5%) underwent FTT, 51 (25.5%) underwent PFA, and 78 (39.0%) underwent BKA. Median postoperative time points of survey completion between FTT (6.2 months, IQR: 23.1), PFA (6.8 months, IQR: 15.5), and BKA (11.1 months, IQR: 21.3) patients were comparable (P = 0.8672). Most patients were male (n = 92, 76.0%) with an average age and body mass index (BMI) of 61.8 ± 12.6 years and 30.3 ± 7.0 kg/m2, respectively. Comorbidities for FTT, PFA, and BKA patients included diabetes mellitus (DM; 60.6% vs 84.2% vs 69.2%; P = 0.165), peripheral vascular disease (PVD; 48.5% vs 47.4% vs 42.3%; P = 0.790), and chronic kidney disease (CKD; 12.1% vs 42.1% vs 30.8%; P = 0.084). No significant differences were observed between FTT, PFA, and BKA patients in mean overall PROMIS-3a T-scores (49.6 ± 14.8 vs 54.2 ± 11.8 vs 49.6 ± 13.7; P = 0.098), LEFS scores (37.5 ± 18.0 vs 34.6 ± 18.3 vs 38.5 ± 19.4; P = 0.457), or SF-12 scores (29.6 ± 4.1 vs 29.5 ± 2.9 vs 29.0 ± 4.0; P = 0.298)., Conclusion: Patients receiving FTT, PFA, or BKA for chronic LE wounds achieve comparable levels of LE function, pain, and QoL postoperatively. Patient-centered functionally based surgical management for chronic LE wounds using interdisciplinary care, preoperative medical optimization, and proper patient selection optimizes postoperative PROMs., Competing Interests: Conflicts of interest disclosures: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Advanced airway management is a skill that is used every day in patient care settings throughout the world. Albeit common, it is not benign. Advanced airway management may either be elective or urgent; in either case, it may result in significant patient morbiidity and mortality. The complications of difficult or failed endotracheal intubation can be severe and include death or permanent neurologic injury. Difficulty or failure with advanced airway management often coincides with the onset of hypoxia. The onset of hypoxia affects both the patient and the airway manager. While hypoxemia may result in dysrhythmias and ultimately cardiac arrest for the patient, it adds time pressure and stress to the airway manager, and thus may impact successful performance. In this review, we will discuss how to identify patients at risk for rapid desaturation during advanced airway management. Additionally, methods of peri-oxygenation throughout the performance of airway management will be discussed., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This review highlights the development of plant proteins from a wide variety of sources, as most of the research and development efforts to date have been limited to a few sources including soy, chickpea, wheat, and pea. The native structure of plant proteins during production and their impact on food colloids including emulsions, foams, and gels are considered in relation to their fundamental properties, while highlighting the recent developments in the production and processing technologies with regard to their impacts on the molecular properties and aggregation of the proteins. The ability to quantify structural, morphological, and rheological properties can provide a better understanding of the roles of plant proteins in food systems. The applications of plant proteins as dairy and meat alternatives are discussed from the perspective of food structure formation. Future directions on the processing of plant proteins and potential applications are outlined to encourage the generation of more diverse plant-based products., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The parasitic mite, Varroa destructor has posed a threat to the health and survival of European honey bees, Apis mellifera worldwide. There is a prevailing belief that small comb cells could provide a management tool against Varroa mites. However, the hypothesis that smaller cells can impede Varroa reproduction has not been fully tested. Here, we tested this hypothesis under laboratory conditions by using two distinct Varroa in vitro rearing systems: one involved gelatin capsules of different sizes, specifically size 00 (0.95 mL) versus size 1 (0.48 mL), and the second consisted of brood comb cells drawn on 3D printed foundations with varying cell sizes, ranging from 5.0 mm to 7.0 mm at 0.5 mm intervals., Results: The results showed that mother mites in size 00 cells had significantly lower fecundity and fertility compared to those in size 1 cells. Interestingly, the reproductive suppression in larger cells could be reversed by adding an extra worker larva. Similarly, gonopore size of mother mites was smaller in size 00 cells, but restored with another host larva. Furthermore, both the fecundity and fertility of mother mites decreased linearly with the size of brood comb cells., Conclusions: Our results suggest that the reproduction of V. destructor is hindered by larger cells, possibly because larger brood cells disperse or weaken host volatile chemical cues that are crucial for Varroa reproduction. The insights derived from this study are expected to hold significant implications for the implementation of Varroa management programs. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

During the fetal period, oxygenated blood from the placenta flows through the umbilical vein (UV), portal sinus, ductus venosus (DV), and inferior vena cava (IVC) to the heart. This venous route varies regionally in many aspects. Herein, we sought to characterize the venous route's morphological features and regional differences during embryonic and early-fetal periods. Twenty-nine specimens were selected for high-resolution digitized imaging; 18 embryos were chosen for histological analysis. The venous route showed a primitive, large, S-shaped curved morphology with regional narrowing and dilation at Carnegie stage (CS) 15. Regional differences in vessel-wall differentiation became apparent from approximately CS20. The vessel wall was poorly developed in most DV parts; local vessel-wall thickness at the inlet was first detected at CS20. The lumen of the venous route changed from a nonuniform shape to a relatively round and uniform morphology after CS21. During the early-fetal period, two large bends were observed around the passage of the umbilical ring and at the inlet of the liver. The length ratio of the extrahepatic UV to the total venous route increased. The sectional area gradually increased during embryonic development, whereas differences in sectional area between the DV, UV, and IVC became more pronounced in the early-fetal period. Furthermore, differences in the sectional area between the narrowest part of the DV and other hepatic veins and the transverse sinus became more pronounced. In summary, the present study described morphological, morphometric, and histological changes in the venous route throughout embryonic and early-fetal development, clarifying regional characteristics., (© 2024 American Association for Anatomy.)

Purpose: Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA)., Methods: An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician-researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements., Results: The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care., Conclusion: Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Various female reproductive disorders affect millions of women worldwide and bring many troubles to women's daily life. Let alone, gynecological cancer (such as ovarian cancer and cervical cancer) is a severe threat to most women's lives. Endometriosis, pelvic inflammatory disease, and other chronic diseases-induced pain have significantly harmed women's physical and mental health. Despite recent advances in the female reproductive field, the existing challenges are still enormous such as personalization of disease, difficulty in diagnosing early cancers, antibiotic resistance in infectious diseases, etc. To confront such challenges, nanoparticle-based imaging tools and phototherapies that offer minimally invasive detection and treatment of reproductive tract-associated pathologies are indispensable and innovative. Of late, several clinical trials have also been conducted using nanoparticles for the early detection of female reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics. However, these nanoparticle trials are still nascent due to the body's delicate and complex female reproductive system. The present review comprehensively focuses on emerging nanoparticle-based imaging and phototherapies applications, which hold enormous promise for improved early diagnosis and effective treatments of various female reproductive organ diseases., (© 2023 Wiley‐VCH GmbH.)

The existence of LUCA in the distant past is the logical consequence of the binary mechanism of cell division. The biosphere in which LUCA and contemporaries were living was the product of a long cellular evolution from the origin of life to the second age of the RNA world. A parsimonious scenario suggests that the molecular fabric of LUCA was much simpler than those of modern organisms, explaining why the evolutionary tempo was faster at the time of LUCA than it was during the diversification of the three domains. Although LUCA was possibly equipped with a RNA genome and most likely lacked an ATP synthase, it was already able to perform basic metabolic functions and to produce efficient proteins. However, the proteome of LUCA and its inferred metabolism remains to be correctly explored by in-depth phylogenomic analyses and updated datasets. LUCA was probably a mesophile or a moderate thermophile since phylogenetic analyses indicate that it lacked reverse gyrase, an enzyme systematically present in all hyperthermophiles. The debate about the position of Eukarya in the tree of life, either sister group to Archaea or descendants of Archaea, has important implications to draw the portrait of LUCA. In the second alternative, one can a priori exclude the presence of specific eukaryotic features in LUCA. In contrast, if Archaea and Eukarya are sister group, some eukaryotic features, such as the spliceosome, might have been present in LUCA and later lost in Archaea and Bacteria. The nature of the LUCA virome is another matter of debate. I suggest here that DNA viruses only originated during the diversification of the three domains from an RNA-based LUCA to explain the odd distribution pattern of DNA viruses in the tree of life., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This case-control study investigated the long-term evolution of multidrug-resistant bacteria (MDRB) over a 5-year period associated with the use of selective oropharyngeal decontamination (SOD) in the intensive care unit (ICU). In addition, effects on health care-associated infections and ICU mortality were analysed., Methods: We investigated patients undergoing mechanical ventilation > 48 h in 11 adult ICUs located at 3 campuses of a university hospital. Administrative, clinical, and microbiological data which were routinely recorded electronically served as the basis. We analysed differences in the rates and incidence densities (ID, cases per 1000 patient-days) of MDRB associated with SOD use in all patients and stratified by patient origin (outpatient or inpatient). After propensity score matching, health-care infections and ICU mortality were compared., Results: 5034 patients were eligible for the study. 1694 patients were not given SOD. There were no differences in the incidence density of MDRB when SOD was used, except for more vancomycin-resistant Enterococcus faecium (0.72/1000 days vs. 0.31/1000 days, p < 0.01), and fewer ESBL-producing Klebsiella pneumoniae (0.22/1000 days vs. 0.56/1000 days, p < 0.01). After propensity score matching, SOD was associated with lower incidence rates of ventilator-associated pneumonia and death in the ICU but not with ICU-acquired bacteremia or urinary tract infection., Conclusions: Comparisons of the ICU-acquired MDRB over a 5-year period revealed no differences in incidence density, except for lower rate of ESBL-producing Klebsiella pneumoniae and higher rate of vancomycin-resistant Enterococcus faecium with SOD. Incidence rates of ventilator-associated pneumonia and death in the ICU were lower in patients receiving SOD., (© 2022. The Author(s).)

Influenza viruses have been posing a great threat to public health and animal industry. The developed vaccines have been widely used to reduce the risk of potential pandemic; however, the ongoing antigenic drift makes influenza virus escape from host immune response and hampers vaccine efficacy. Until now, the genetic basis of antigenic variation remains largely unknown. In this study, we used A/swine/Guangxi/18/2011 (GX/18) and A/swine/Guangdong/104/2013 (GD/104) as models to explore the molecular determinant for antigenic variation of Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs) and found that the GD/104 virus exhibited 32- to 64-fold lower antigenic cross-reactivity with antibodies against GX/18 virus. Therefore, we generated polyclonal antibodies against GX/18 or GD/104 virus and a monoclonal antibody (mAb), named mAb102-95, targeted to the haemagglutinin (HA) protein of GX/18 virus and found that a single amino acid substitution at position 158 in HA protein substantially altered the antigenicity of the virus. The reactivity of GX/18 virus containing G158E mutation with the mAb102-95 decreased eightfold than that of the parental strain. Contrarily, the reactivity of GD/104 virus bearing E158G mutation with the mAb102-95 increased by 32 times as compared with that of the parental virus. Structural analysis showed that the amino acid mutation from G to E was accompanied with the R group changing from -H to -(CH 2 ) 2 -COOH. The induced steric effect and increased hydrophilicity of HA protein surface probably jointly contributed to the antigenic drift of EA H1N1 SIVs. Our study provides experimental evidence that G158E mutation in HA protein affects the antigenic property of EA H1N1 SIVs and widens our horizon on the antigenic drift of influenza virus., (© 2021 Wiley-VCH GmbH.)