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Monocytes, as well as downstream macrophages and dendritic cells, are essential players in the immune system, fulfilling key roles in homeostasis as well as in inflammatory conditions. Conventionally, driven by studies on reporter models, mouse monocytes are categorized into a classical and a non-classical subset based on their inversely correlated surface expression of Ly6C/CCR2 and CX3CR1. Here, we aimed to challenge this concept by antibody staining and reporter mouse models. Therefore, we took advantage of Cx3cr1GFP and Ccr2RFP reporter mice, in which the respective gene was replaced by a fluorescent reporter protein gene. We analyzed the expression of CX3CR1 and CCR2 by flow cytometry using several validated fluorochrome-coupled antibodies and compared them with the reporter gene signal in these reporter mouse strains. Although we were able to validate the specificity of the fluorochrome-coupled flow cytometry antibodies, mouse Ly6Chigh classical and Ly6Clow non-classical monocytes showed no differences in CX3CR1 expression levels in the peripheral blood and spleen when stained with these antibodies. On the contrary, in Cx3cr1GFP reporter mice, we were able to reproduce the inverse correlation of the CX3CR1 reporter gene signal and Ly6C surface expression. Furthermore, differential CCR2 surface expression correlating with the expression of Ly6C was observed by antibody staining, but not in Ccr2RFP reporter mice. In conclusion, our data suggest that phenotyping strategies for mouse monocyte subsets should be carefully selected. In accordance with the literature, the suitability of CX3CR1 antibody staining is limited, whereas for CCR2, caution should be applied when using reporter mice. [ABSTRACT FROM AUTHOR]

The layup quality of prepreg fibers onto complex surfaces is the most concerned issue in automated fiber placement (AFP), which is intimately related to the contact stress in tractive rolling contact. An analytical model of tractive rolling contact is proposed in this paper to clarify the defects mechanism during the AFP process, which considers the mold curvatures, mechanical properties of contacted objects, and pose information to make it suitable for irregular surfaces and arbitrary conditions. Classical Hertz theory in this model is expanded to 3D contact area, and multi‐scale deformations are united in the accurate calculation of contact stress under geometric constraints. Based on the model, the phenomena of adhesion, microslip, and the transition between them in AFP are systematically analyzed. For engineering applications, a discrete processing strategy is proposed to quickly obtain the local curvatures of the mold. Additionally, an algorithm is designed to calculate the contact stress of any path. Experimental results on an aircraft component demonstrate the accuracy of the proposed model in restoring the contact stress distribution during AFP. In conjunction with specific layup information, this model exhibits utility in forecasting laying defects and parameter optimization. Highlights: An analytical modeling approach based on Hertz theory is proposed to calculate the contact stress in automated fiber placement.A model‐based algorithm is designed and combined with the proposed discrete scheme to quickly restore the contact stress distribution.Contact states related to stress are systematically investigated and defects analysis based on computational mechanics results is illustrated. [ABSTRACT FROM AUTHOR]

Trends in moral psychology largely support the role that emotion plays in moral cognition with human lesion studies offering the most compelling evidence to date. Specifically, data from ventromedial prefrontal cortex (vmPFC) patients on moral judgment tasks has suggested the necessity of having intact emotion to behave in morally appropriate ways. However, patients with vmPFC damage also have deficits in a variety of complex judgment and decision-making tasks, regardless of whether emotion is involved. This paper argues that a basic information processing perspective of vmPFC functionality is a better interpretation of vmPFC patient deficits, specifically with the vmPFC being necessary for value assessment rather than being specific to emotion. [ABSTRACT FROM AUTHOR]

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This paper presents evidence that social categorization affects spontaneous level‐2 visual perspective taking (L2PT) differently depending on the type of social category in 8‐year‐old. In Experiment 1 (N = 46), children were paired with same‐age peers, who belonged to the same or a different minimal group. In Experiment 2 (N = 42) children participated with an adult confederate, who either shared their cultural group membership or was a member of an out‐group (inferred from a linguistic cue, accent). In Experiment 3 (N = 80), children were acting together with an adult confederate who was at the same time a member of the same or a different minimal group and shared their linguistic membership. This allowed us to investigate how these social categories influence each other. Spontaneous L2PT was not affected by the minimal group manipulation. However, accent weakened L2PT when it implied that the task partner belonged to an out‐group. When both category cues were present, accent—that could be an indicator of shared knowledge attribution—played a more pronounced role in attenuating L2PT. It is argued that social categories that are indicative of the partner's knowledge states but not ad hoc groups influence spontaneous mentalizing. [ABSTRACT FROM AUTHOR]

Background: There is an increased tendency towards adopting minimally invasive interventions in dentistry, supported by advancement in materials and techniques. However, the decision‐making process in choosing conservative or invasive treatments is influenced by several factors, particularly in permanent teeth with irreversible pulpitis. Objectives: The objective of the study was to systematically review the literature regarding factors that influence decision‐making for vital pulp therapy (VPT) as definitive treatment option in permanent mature teeth diagnosed with irreversible pulpitis. Methods: Two independent reviewers searched five electronic databases (PubMed, Embase, Web of Science, Scopus and Cochrane Library). Grey literature was searched through Google Scholar and contact with experts. Defined search keys were applied, and all peer‐reviewed literature published with no language nor publication date limits were included. The All studies investigating the factors influencing treatment decision‐making in mature permanent teeth with irreversible pulpitis were included. The quality of included studies was assessed by two independent reviewers using the Joanna Briggs Institute quality assessment tool. Results: Six articles were included in the review. All included studies used questionnaires to characterize clinician preferences and attitudes in choosing treatment options for mature permanent teeth with irreversible pulpitis. The available evidence suggests that dentist‐related factors have a significant influence on the chosen treatment in teeth with irreversible pulpitis, with speciality training and years of experience influencing the choice of VPT over other treatment options. COVID‐19 reportedly swayed the dentists' decision to favour VPT. Only one article studied the influence of patient‐related factors, such as age and presence of spontaneous pain on decision‐making. Of note, a history of cardiovascular disease moved dentists towards prescribing VPT. Discussion: Collectively, the included studies demonstrated an overriding influence of dentist‐related factors on choosing among treatment options for painful teeth diagnosed with irreversible pulpitis. Patient‐related factors were acknowledged but there are also potential factors such as socio‐economic constraints that were not included in the component studies. Conclusion: In teeth with irreversible pulpitis clinicians educational background influence the decision towards a specific treatment option. Further data, preferably derived from clinical records, is necessary in future investigations to explore the effect of other important factors related to both dentists and patients. Registration: PROSPERO database (CRD42022339653). [ABSTRACT FROM AUTHOR]

Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κβ inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Cervical kinesthesia is an important part of movement control and of great importance for daily function. Previous research on kinesthesia in whiplash-associated disorders (WAD) has focused on grades I-II. More research is needed on WAD grade III. The aim of this study was to investigate cervical kinesthesia in individuals with WAD grades II-III before and after a neck-specific exercise intervention and compare them to healthy controls. Methods: A prospective, case-control study with a treatment arm (n = 30) and a healthy control arm (n = 30) was conducted in Sweden. The WAD group received a neck-specific exercise program for 12 weeks. The primary outcome to evaluate kinesthesia was neck movement control (the Fly test). Secondary outcomes were neck disability, dizziness and neck pain intensity before and after the Fly test. Outcomes were measured at baseline and post-treatment. The control arm underwent measurements at baseline except for the dizziness questionnaire. A linear mixed model was used to evaluate difference between groups (WAD and control) and over time, with difficulty level in the Fly test and gender as factors. Results: Between-group analysis showed statistically significant differences in three out of five kinesthetic metrics (p = 0.002 to 0.008), but not for the WAD-group follow-up versus healthy control baseline measurements. Results showed significant improvements for the WAD-group over time for three out of five kinaesthesia metrics (p < 0.001 to 0.008) and for neck disability (p < 0.001) and pain (p = 0.005), but not for dizziness (p = 0.70). Conclusions: The exercise program shows promising results in improving kinesthesia and reducing neck pain and disability in the chronic WAD phase. Future research might benefit from focusing on adding kinesthetic exercises to the exercise protocol and evaluating its beneficial effects on dizziness or further improvement in kinesthesia. Impact statement: Kinesthesia can be improved in chronic WAD patients without the use of specific kinesthetic exercises. Trial registration: ClinicalTrials.gov (NCT03664934), first registration approved 11/09/2018. [ABSTRACT FROM AUTHOR]

To address the challenges of the twenty-first century, particularly the negative effects of climate change, mitigation measures such as Nature-based Solutions (NbS) are being employed. Vegetation, being a part of various NbS interventions, provides different ecosystem services that help combat current climate-related vulnerabilities. This research aims to illustrate the connection between plants' contribution to adapting to climate change and the creation of more sustainable spaces, focusing on the usage of bioretention systems (BRs) as an example of NbS. Some of the main aspects of how vegetation is selected for BRs according to qualities that may contribute to developing sustainable landscapes, along with providing key features of plants' adaptation, different taxonomic data, and specific plant species that have been demonstrated to be good candidates for planting in BRs, are also discussed. Therefore, the importance of this paper is in providing a comprehensive systematization of vegetation with insightful suggestions on plant species for future BR implementation. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is characterized by an elevated risk for cerebrovascular disease including stroke. One mechanism that may contribute to this heightened risk is an impairment in cerebrovascular carbon dioxide reactivity (CVR). We compared CVR between CKD patients stages III–IV and controls (CON) without CKD but matched for hypertension and diabetes status. CVR was measured via 5% CO2 inhalation followed by voluntary hyperventilation in 14 CKD and 11 CON participants while mean arterial pressure, end‐tidal carbon dioxide, and middle cerebral artery blood velocity (MCAv) were measured continuously. CVR was quantified as the linear relationship between etCO2 and MCAv. We observed no difference in CVR between groups. Hypercapnic CVR: CKD = 1.2 ± 0.9 cm/s/mm Hg, CON = 1.3 ± 0.8 cm/s/mm Hg, hypocapnic CVR: CKD = 1.3 ± 0.9 cm/s/mm Hg, CON = 1.5 ± 0.7 cm/s/mm Hg, integrated CVR: CKD = 1.5 ± 1.1 cm/s/mm Hg, CON = 1.7 ± 0.8 cm/s/mm Hg, p ≥ 0.48. Unexpectedly, CVR was inversely related to estimated glomerular filtration rate in CKD (R2 = 0.37, p = 0.02). We report that CVR remains intact in CKD and is inversely related to eGFR. These findings suggest that other mechanisms beyond CVR contribute to the elevated stroke risk observed in CKD. [ABSTRACT FROM AUTHOR]

The purpose of the study was to evaluate the influence of the simulated digestion process on the content of the standard cholesterol and this sterol found in fats. Additionally, the content of cholesterol oxides formed after the thermal processing of fats and standard of cholesterol was investigated in samples after performing in vitro digestion procedure. The next step was to evaluate changes in the concentration of cholesterol and cholesterol oxidation products in all analyzed samples. On that basis, the bioaccessibility of cholesterol and cholesterol oxidation products in analyzed samples was established. Cholesterol bioaccessibility ranged from 1.05% to 28.38% in thermally processed samples, while cholesterol standard samples accounted for 7.16% and 5.00%. The bioaccessibility of cholesterol oxides found in analyzed fats and fats with 0.2% addition of cholesterol standard ranged from 5.44% to 19.20%, and only in butter heated at 180°C per 1 h, it reached 47.61%. Studies show that cholesterol present in the food matrix is better protected from degradation, and oxidation during thermal treatment than the standard of cholesterol (processed without food matrix). The results of this study confirm that the bioavailability of cholesterol and its oxides are influenced by the food matrix. Practical applications: The results of our experiment can be used for further scientific analyzes related to the process of estimating the bioavailability of cholesterol and cholesterol oxidation products, which can be found in food products. [ABSTRACT FROM AUTHOR]

Recently, studies have reported a correlation that individuals with diabetes show an increased risk of developing Alzheimer's disease (AD). Mulberry leaves, serving as both a traditional medicinal herb and a food source, exhibit significant hypoglycemic and antioxidative properties. The flavonoid compounds in mulberry leaf offer therapeutic effects for relieving diabetic symptoms and providing neuroprotection. However, the mechanisms of this effect have not been fully elucidated. This investigation aimed to investigate the combined effects of specific mulberry leaf flavonoids (kaempferol, quercetin, rhamnocitrin, tetramethoxyluteolin, and norartocarpetin) on both type 2 diabetes mellitus (T2DM) and AD. Additionally, the role of the gut microbiota in these two diseases' treatment was studied. Using network pharmacology, we investigated the potential mechanisms of flavonoids in mulberry leaves, combined with gut microbiota, in combating AD and T2DM. In addition, we identified protein tyrosine phosphatase 1B (PTP1B) as a key target for kaempferol in these two diseases. Molecular docking and molecular dynamics simulations showed that kaempferol has the potential to inhibit PTP1B for indirect treatment of AD, which was proven by measuring the IC50 of kaempferol (279.23 μM). The cell experiment also confirmed the dose-dependent effect of kaempferol on the phosphorylation of total cellular protein in HepG2 cells. This research supports the concept of food–medicine homology and broadens the range of medical treatments for diabetes and AD, highlighting the prospect of integrating traditional herbal remedies with modern medical research. [ABSTRACT FROM AUTHOR]

The persisting presence of opportunistic pathogens like Pseudomonas aeruginosa poses a significant threat to many immunocompromised cancer patients with pulmonary infections. This review highlights the complexity of interactions in the host's defensive eicosanoid signaling network and its hijacking by pathogenic bacteria to their own advantage. Human lipoxygenases (ALOXs) and their mouse counterparts are integral elements of the innate immune system, mostly operating in the pro-inflammatory mode. Taking into account the indispensable role of inflammation in carcinogenesis, lipoxygenases have counteracting roles in this process. In addition to describing the structure-function of lipoxygenases in this review, we discuss their roles in such critical processes as cancer cell signaling, metastases, death of cancer and immune cells through ferroptosis, as well as the roles of ALOXs in carcinogenesis promoted by pathogenic infections. Finally, we discuss perspectives of novel oncotherapeutic approaches to harness lipoxygenase signaling in tumors. [ABSTRACT FROM AUTHOR]

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal–glial–immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications. [ABSTRACT FROM AUTHOR]

An organism's ability to function properly depends not solely on its diet but also on the intake of nutrients and non-nutritive bioactive compounds that exert immunomodulatory effects. This principle applies both to healthy individuals and, in particular, to those with concomitant chronic conditions, such as type 2 diabetes. However, the current food industry and the widespread use of highly processed foods often lead to nutritional deficiencies. Numerous studies have confirmed the occurrence of immune system dysfunction in patients with type 2 diabetes. This article elucidates the impact of specific nutrients on the immune system function, which maintains homeostasis of the organism, with a particular emphasis on type 2 diabetes. The role of macronutrients, micronutrients, vitamins, and selected substances, such as omega-3 fatty acids, coenzyme Q10, and alpha-lipoic acid, was taken into consideration, which outlined the minimum range of tests that ought to be performed on patients in order to either directly or indirectly determine the severity of malnutrition in this group of patients. [ABSTRACT FROM AUTHOR]

A large number of epidemiological studies have shown that consumption of fruits, vegetables, and beverages rich in (poly)phenols promote numerous health benefits from cardiovascular to neurological diseases. Evidence on (poly)phenols has been applied mainly to flavonoids, yet the role of phenolic acids has been largely overlooked. Such phenolics present in food combine with those resulting from gut microbiota catabolism of flavonoids and chlorogenic acids and those produced by endogenous pathways, resulting in large concentrations of low molecular weight phenolic metabolites in human circulation. Independently of the origin, in human intervention studies using diets rich in (poly)phenols, a total of 137 low molecular weight phenolic metabolites have been detected and quantified in human circulation with largely unknown biological function. In this review, we will pinpoint two main aspects of the low molecular weight phenolic metabolites: (i) the microbiota responsible for their generation, and (ii) the analysis (quali- and quantitative) in human circulation and their respective pharmacokinetics. In doing so, we aim to drive scientific advances regarding the ubiquitous roles of low molecular weight phenolic metabolites using physiologically relevant concentrations and under (patho)physiologically relevant conditions in humans., (© 2022 The Authors. Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

In this work, we report the structural and magnetic characterization of two new B-site rock-salt ordered double perovskites ALaCoTeO6 (A = K+ and Na+) with mixed A-site cations. KLaCoTeO6 crystallizes in the space group P4/nmm with a long-range ordering degree of 84.8% for the A-site K+/La3+ cations, whereas NaLaCoTeO6 adopts an unexpected triclinically distorted I1¯-structure with Na/La3+ disordering, validated by combined Rietveld refinements against high-resolution neutron diffraction data and Cu Kα1 X-ray powder diffraction data. Magnetic susceptibility at low temperatures shows clear antiferromagnetic (AFM) transitions for both compounds. KLaCoTeO6 exhibits the highest AFM transition temperature of 20 K amongst all the Co/Te-ordered 3C-type A2CoTeO6 (A = Pb2+, Sr2+, and Ca2+) and ALaCoTeO6 double perovskites due to its larger Co2+–O–Te6+ bond angle and A-site cationic ordering-induced larger distortion of the Co2+-based face-centered cubic sublattice. Moreover, we found that the average radius of the A-site cations plays a decisive role in the AFM transition temperatures of all these ordered double perovskites, that is, a larger A-site cation always results in a higher AFM transition temperature. This provides a strategy to subtly manipulate the magnetic properties of ordered double perovskites. [ABSTRACT FROM AUTHOR]

Background: Retinal degeneration results from disruptions in retinal homeostasis due to injury, disease, or aging and triggers peripheral leukocyte infiltration. Effective immune responses rely on coordinated actions of resident microglia and recruited macrophages, critical for tissue remodeling and repair. However, these phagocytes also contribute to chronic inflammation in degenerated retinas, yet the precise coordination of immune response to retinal damage remains elusive. Recent investigations have demonstrated that phagocytic cells can produce extracellular traps (ETs), which are a source of self-antigens that alter the immune response, which can potentially lead to tissue injury. Methods: Innovations in experimental systems facilitate real-time exploration of immune cell interactions and dynamic responses. We integrated in vivo imaging with ultrastructural analysis, transcriptomics, pharmacological treatments, and knockout mice to elucidate the role of phagocytes and their modulation of the local inflammatory response through extracellular traps (ETs). Deciphering these mechanisms is essential for developing novel and enhanced immunotherapeutic approaches that can redirect a specific maladaptive immune response towards favorable wound healing in the retina. Results: Our findings underscore the pivotal role of innate immune cells, especially macrophages/monocytes, in regulating retinal repair and inflammation. The absence of neutrophil and macrophage infiltration aids parenchymal integrity restoration, while their depletion, particularly macrophages/monocytes, impedes vascular recovery. We demonstrate that macrophages/monocytes, when recruited in the retina, release chromatin and granular proteins, forming ETs. Furthermore, the pharmacological inhibition of ETosis support retinal and vascular repair, surpassing the effects of blocking innate immune cell recruitment. Simultaneously, the absence of ETosis reshapes the inflammatory response, causing neutrophils, helper, and cytotoxic T-cells to be restricted primarily in the superficial capillary plexus instead of reaching the damaged photoreceptor layer. Conclusions: Our data offer novel insights into innate immunity's role in responding to retinal damage and potentially help developing innovative immunotherapeutic approaches that can shift the immune response from maladaptive to beneficial for retinal regeneration. [ABSTRACT FROM AUTHOR]

Background. Diabetes mellitus (DM) presents a significant global health challenge with considerable cardiovascular implications. Coenzyme Q10 (CoQ10) has gained recognition for its potential as a natural antioxidant supplement in the management of diabetes and its associated cardiovascular complications. Aim. This comprehensive review systematically examines the scientific rationale underlying the therapeutic properties of CoQ10 in mitigating the impact of diabetes and its cardiovascular consequences. The analysis encompasses preclinical trials (in vitro and in vivo) and clinical studies evaluating the efficacy and mechanisms of action of CoQ10. Result & Discussion. Findings reveal that CoQ10, through its potent antioxidant and anti-inflammatory attributes, demonstrates significant potential in reducing oxidative stress, ameliorating lipid profiles, and regulating blood pressure, which are crucial aspects in managing diabetes-induced cardiovascular complications. CoQ10, chemically represented as C59H90O4, was administered in capsule form for human studies at doses of 50, 100, 150, 200, and 300 mg per day and at concentrations of 10 and 20 μM in sterile powder for experimental investigations and 10 mg/kg in powder for mouse studies, according to the published research. Clinical trials corroborate these preclinical findings, demonstrating improved glycemic control, lipid profiles, and blood pressure in patients supplemented with CoQ10. Conclusion. In conclusion, CoQ10 emerges as a promising natural therapeutic intervention for the comprehensive management of diabetes and its associated cardiovascular complications. Its multifaceted impacts on the Nrf2/Keap1/ARE pathway, oxidative stress, and metabolic regulation highlight its potential as an adjunct in the treatment of diabetes and related cardiovascular disorders. However, further extensive clinical investigations are necessary to fully establish its therapeutic potential and assess potential synergistic effects with other compounds. [ABSTRACT FROM AUTHOR]

While polyphenol consumption is often associated with an increased abundance of beneficial microbes and decreased opportunistic pathogens, these relationships are not completely described for polyphenols consumed via habitual diet, including culinary herb and spice consumption. This analysis of the International Cohort on Lifestyle Determinants of Health (INCLD Health) cohort uses a dietary questionnaire and 16s microbiome data to examine relationships between habitual polyphenol consumption and gut microbiota in healthy adults (n = 96). In this exploratory analysis, microbial taxa, but not diversity measures, differed by levels of dietary polyphenol consumption. Taxa identified as exploratory biomarkers of daily polyphenol consumption (mg/day) included Lactobacillus, Bacteroides, Enterococcus, Eubacterium ventriosum group, Ruminococcus torques group, and Sutterella. Taxa identified as exploratory biomarkers of the frequency of polyphenol-weighted herb and spice use included Lachnospiraceae UCG-001, Lachnospiraceae UCG-004, Methanobrevibacter, Lachnoclostridium, and Lachnotalea. Several of the differentiating taxa carry out activities important for human health, although out of these taxa, those with previously described pro-inflammatory qualities in certain contexts displayed inverse relationships with polyphenol consumption. Our results suggest that higher quantities of habitual polyphenol consumption may support an intestinal environment where opportunistic and pro-inflammatory bacteria are represented in a lower relative abundance compared to those with less potentially virulent qualities. [ABSTRACT FROM AUTHOR]

The pollution of soil and aquatic systems by inorganic and organic chemicals has become a global concern. Economical, eco-friendly, and sustainable solutions are direly required to alleviate the deleterious effects of these chemicals to ensure human well-being and environmental sustainability. In recent decades, biochar has emerged as an efficient material encompassing huge potential to decontaminate a wide range of pollutants from soil and aquatic systems. However, the application of raw biochars for pollutant remediation is confronting a major challenge of not getting the desired decontamination results due to its specific properties. Thus, multiple functionalizing/modification techniques have been introduced to alter the physicochemical and molecular attributes of biochars to increase their efficacy in environmental remediation. This review provides a comprehensive overview of the latest advancements in developing multiple functionalized/modified biochars via biological and other physiochemical techniques. Related mechanisms and further applications of multiple modified biochar in soil and water systems remediation have been discussed and summarized. Furthermore, existing research gaps and challenges are discussed, as well as further study needs are suggested. This work epitomizes the scientific prospects for a complete understanding of employing modified biochar as an efficient candidate for the decontamination of polluted soil and water systems for regenerative development. [ABSTRACT FROM AUTHOR]

Anthocyanins, due to their antioxidant effects, are candidates to reduce inflammation and the risk of inflammatory diseases. Therefore, through conducting a systematic review and meta‐analysis, we tried to find the effect of purified anthocyanins on serum levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α). Databases including, ISI Web of Science, Scopus, ClinicalTrials.gov, PubMed, and Cochrane Library were searched up to June 2023. The meta‐analysis was done by calculating mean differences and their standard deviations. Calculating the statistical heterogeneity of intervention effects was performed through I‐squared statistics and Cochran's Q test. The pooled estimate showed a significant decrease in serum levels of CRP, TNF‐α, and IL‐6 (weighted mean difference (WMD) = −0.12 mg/L, 95% confidence interval (CI) = −0.21 to −0.02, p = 0.013; WMD = −1.37 pg/mL, 95% CI = −1.79 to −0.96; p < 0.001; WMD = −1.43 pg/mL, 95% CI = −1.87 to −1.00; p < 0.001, respectively). Subgroup analysis results revealed purified anthocyanins significantly decreased serum levels of CRP among participants with serum levels of CRP≥1.52 mg/L, at‐risk/unhealthy status, and in trials with intervention duration ≥84 days, anthocyanins dose ≥320 mg/day, and sample size ≥85 subjects. Regarding TNF‐α and IL‐6, out results showed that there was a significant effect of purified anthocyanins on serum levels of TNF‐α and IL‐6 in most subgroups. The results of our study indicated that purified anthocyanins significantly decreased serum levels of CRP, TNF‐α, and IL‐6. However, further high‐quality studies are needed to firmly establish the efficacy of purified anthocyanins. [ABSTRACT FROM AUTHOR]

Cellular senescence and the senescence‐associated secretory phenotype (SASP) contribute to age‐related arterial dysfunction, in part, by promoting oxidative stress and inflammation, which reduce the bioavailability of the vasodilatory molecule nitric oxide (NO). In the present study, we assessed the efficacy of fisetin, a natural compound, as a senolytic to reduce vascular cell senescence and SASP factors and improve arterial function in old mice. We found that fisetin decreased cellular senescence in human endothelial cell culture. In old mice, vascular cell senescence and SASP‐related inflammation were lower 1 week after the final dose of oral intermittent (1 week on—2 weeks off—1 weeks on dosing) fisetin supplementation. Old fisetin‐supplemented mice had higher endothelial function. Leveraging old p16‐3MR mice, a transgenic model allowing genetic clearance of p16INK4A‐positive senescent cells, we found that ex vivo removal of senescent cells from arteries isolated from vehicle‐ but not fisetin‐treated mice increased endothelium‐dependent dilation, demonstrating that fisetin improved endothelial function through senolysis. Enhanced endothelial function with fisetin was mediated by increased NO bioavailability and reduced cellular‐ and mitochondrial‐related oxidative stress. Arterial stiffness was lower in fisetin‐treated mice. Ex vivo genetic senolysis in aorta rings from p16‐3MR mice did not further reduce mechanical wall stiffness in fisetin‐treated mice, demonstrating lower arterial stiffness after fisetin was due to senolysis. Lower arterial stiffness with fisetin was accompanied by favorable arterial wall remodeling. The findings from this study identify fisetin as promising therapy for clinical translation to target excess cell senescence to treat age‐related arterial dysfunction. [ABSTRACT FROM AUTHOR]

A total of 180 growing pigs (Duroc × Landrace × Yorkshire) with an initial body weight (BW) of 23.58 ± 0.8 kg were used in this experiment. According to initial BW and sex, pigs were randomly allotted three dietary treatments, 12 replicates (pen) per treatment, and five pigs per pen. The three dietary treatments were basal diet (CON) and basal diet supplemented with either 0.1% Bacillus and Saccharomyces spp.-based probiotics complex (BS1) or 0.2% probiotics complex (BS2). The whole experiment lasted 42 days. The results showed that the BW of pigs fed the BS1 diet was significantly higher than those fed the CON diet on day 42 (P < 0.05). The average daily gain (ADG) of pigs receiving BS1 and BS2 diets was higher than those fed CON diet during days 21–42, whereas during the overall experiment period ADG (P < 0.05) was higher in only BS1 compared with CON group. The NH3 and H2S emissions on day 42 were reduced from the feces of pigs fed probiotic complex-supplemented diets. Therefore, adding 0.1% probiotic complex to the late-phase diet of growing pigs can more effectively improve BW and daily gain and reduce harmful gas emissions. [ABSTRACT FROM AUTHOR]

The dairy–cereal‐based food, known as Doowina, is one of the traditional fermented foods in Iran. We aimed to improve the health‐promoting properties of Doowina by using turnips, butternut squash, and sourdough as a new functional food with high nutritional value and antioxidant activity. Therefore, the physicochemical, microbial, and sensory properties of samples with nutritional supplements (8% turnip and 8% butternut squash) and different concentrations of sourdough (0, 0.5, and 1%) were studied during 0, 3, 6, and 9 days of fermentation time. The results showed that there was no significant difference (p <.05) in the moisture and ash content between the different formulations of Doowina. There was also no significant difference (p <.05) in the phenolic compound content and antioxidant activity of the Doowina samples during the fermentation period. However, the number of lactic acid bacteria (LAB) increased significantly (p <.05) until the 6th day of fermentation, and the protein content decreased significantly (p <.05) in all samples during the fermentation period. According to the results, the samples with butternut squash and sourdough had the highest total phenolic content, the highest antioxidant activity, the highest linoleic acid content, and the highest sensory rating of all samples. [ABSTRACT FROM AUTHOR]

The article informs about American Journal of Respiratory and Critical Care Medicine expresses gratitude to the diligent reviewers who contributed their expertise to manuscript evaluation from January to December 2023. Topic include the extensive list includes professionals from various disciplines, showcasing their commitment to maintaining the journal's high standards through thorough review and analysis.

Sixteen-head automatic tape laying of non-crimped carbon-fibre-reinforced plastic is performed, and the fibre alignment is compared with that produced via hand laying. The effect of fibre alignment is tested via quasi-static and cyclic three-point bending tests. Using the Fill Multilayer (a 16-head tape-laying machine), precision fibre laying of unidirectional fabrics is performed with deliberate misalignment to examine the effect of fibre orientation and investigate the random effect on longitudinal misalignment. The automatic tape-layered coupons are compared with hand-layered carbon fibre tapes to investigate the relationship between the fibre alignment and the flexural strength. A 52% reduction in the fibre alignment scatter is achieved via the Fill Multilayer. Fibre orientation increases lead to a higher flexural strength of 16.08% for Fill Multilayer-made coupons compared with hand-layered samples. An investigation of the correlation between fibre alignment and flexural strength shows that shear-based failure increases exponentially as the alignment decreases. Fill Multilayer-made coupons have a higher void concentration due to ultrasonic welding, but also the highest modulus and flexural strength, as fibre misalignment is reduced to 1.68°, with a modulus degradation of 1.4%. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis‐3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid‐chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro‐inflammatory signaling lipids from ω‐6 poly‐unsaturated fatty acids (PUFAs), including 15‐hydroxyeicosatetraenoic (HETE), 12‐HETE, and 11‐HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro‐resolving lipid mediator from ω‐3 PUFAs, 14(S)‐hydroxy docosahexaenoic acid (14S‐HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor‐outcome patients with sepsis and may serve as targets for future therapies. [ABSTRACT FROM AUTHOR]

Friedreich's ataxia (FRDA) is a rare childhood neurologic disorder, affecting 1 in 50,000 Caucasians. The disease is caused by the abnormal expansion of the GAA repeat sequence in intron 1 of the FXN gene, leading to the reduced expression of the mitochondrial protein frataxin. The disease is characterised by progressive neurodegeneration, hypertrophic cardiomyopathy, diabetes mellitus and musculoskeletal deformities. The reduced expression of frataxin has been suggested to result in the downregulation of endogenous antioxidant defence mechanisms and mitochondrial bioenergetics, and the increase in mitochondrial iron accumulation thereby leading to oxidative stress. The confirmation of oxidative stress as one of the pathological signatures of FRDA led to the search for antioxidants which can be used as therapeutic modality. Based on this observation, antioxidants with different mechanisms of action have been explored for FRDA therapy since the last two decades. In this review, we bring forth all antioxidants which have been investigated for FRDA therapy and have been signed off for clinical trials. We summarise their various target points in FRDA disease pathway, their performances during clinical trials and possible factors which might have accounted for their failure or otherwise during clinical trials. We also discuss the limitation of the studies completed and propose possible strategies for combinatorial therapy of antioxidants to generate synergistic effect in FRDA patients. [ABSTRACT FROM AUTHOR]

Background: Although oral hygiene is closely related to various diseases, it is sub-optimal in the Intensive Care Unit (ICU). Oral care in the ICU is challenged by nursing workloads, low staffing, and higher acuity patients, there are few policies and written guidelines for oral care. Nurses often delegate oral care to nursing assistants (NAs) whose role is overlooked. This study is to explore the perspectives, obstacles, and challenges of NAs in the oral care of the ICU. Methods: A qualitative study and semi-structured interviews were conducted with NAs in three ICU units, and Colaizzi’s phenomenological method was used to analyze the records. Results: Initially, 13 NAs met the inclusion criteria, and two did not participate in this study as they refused to be recorded. Finally, 11 ICU NAs were interviewed, with three receiving face-to-face interviews and eight receiving telephone interviews. Using Colaizzi’s phenomenological method, two themes and eight subthemes emerged from the data, we examined the self-perception, barriers and challenges of NAs regarding oral care and identified the subthemes: (1) The target audience, frequency, and importance; (2) Role; (3) Evaluation; (4) Patient-related factors; (5) Oral care tools; (6) Psychology of NAs; (7) Lack of education and training; (8) Lack of team support. Conclusion: Nursing assistants whose roles are overlooked by the nursing team are important members of the ICU team. Though oral care is closely related to disease prevention, it is rarely considered an essential task. Major barriers to implementing oral care in the ICU environment and patients include the psychological quality of participants, non-standard education and training, and inadequate team support. The expectation is that medical personnel will prioritize oral hygiene and recognize the significance of NAs in nursing work. Furthermore, future ICU oral care should investigate suitable tools and mouthwashes, simplified and standardized processes, standardized training, and multidisciplinary team collaboration. [ABSTRACT FROM AUTHOR]

Glaucoma is a neurodegenerative disease of the retina characterized by the irreversible loss of retinal ganglion cells (RGCs) leading to visual loss. Degeneration of RGCs and loss of their axons, as well as damage and remodeling of the lamina cribrosa are the main events in the pathogenesis of glaucoma. Different molecular pathways are involved in RGC death, which are triggered and exacerbated as a consequence of a number of risk factors such as elevated intraocular pressure (IOP), age, ocular biomechanics, or low ocular perfusion pressure. Increased IOP is one of the most important risk factors associated with this pathology and the only one for which treatment is currently available, nevertheless, on many cases the progression of the disease continues, despite IOP control. Thus, the IOP elevation is not the only trigger of glaucomatous damage, showing the evidence that other factors can induce RGCs death in this pathology, would be involved in the advance of glaucomatous neurodegeneration. The underlying mechanisms driving the neurodegenerative process in glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress and neuroinflammation. In glaucoma, like as other neurodegenerative disorders, the immune system is involved and immunoregulation is conducted mainly by glial cells, microglia, astrocytes, and Müller cells. The increase in IOP produces the activation of glial cells in the retinal tissue. Chronic activation of glial cells in glaucoma may provoke a proinflammatory state at the retinal level inducing blood retinal barrier disruption and RGCs death. The modulation of the immune response in glaucoma as well as the activation of glial cells constitute an interesting new approach in the treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) affects about 200 million people worldwide, causing leakage of blood components into retinal tissues, leading to activation of microglia, the resident phagocytes of the retina, promoting neuronal and vascular damage. The microglial receptor, CX3CR1, binds to fractalkine (FKN), an anti-inflammatory chemokine that is expressed on neuronal membranes (mFKN), and undergoes constitutive cleavage to release a soluble domain (sFKN). Deficiencies in CX3CR1 or FKN showed increased microglial activation, inflammation, vascular damage, and neuronal loss in experimental mouse models. To understand the mechanism that regulates microglia function, recombinant adeno-associated viral vectors (rAAV) expressing mFKN or sFKN were delivered to intact retinas prior to diabetes. High-resolution confocal imaging and mRNA-seq were used to analyze microglia morphology and markers of expression, neuronal and vascular health, and inflammatory mediators. We confirmed that prophylactic intra-vitreal administration of rAAV expressing sFKN (rAAV–sFKN), but not mFKN (rAAV–mFKN), in FKNKO retinas provided vasculo- and neuro-protection, reduced microgliosis, mitigated inflammation, improved overall optic nerve health by regulating microglia-mediated inflammation, and prevented fibrin(ogen) leakage at 4 weeks and 10 weeks of diabetes induction. Moreover, administration of sFKN improved visual acuity. Our results elucidated a novel intervention via sFKN gene therapy that provides an alternative pathway to implement translational and therapeutic approaches, preventing diabetes-associated blindness. [ABSTRACT FROM AUTHOR]

Individual aged with various change in cell and cellular microenvironments and the skeletal system undergoes physiological changes that affect the process of bone fracture healing. These changes are accompanied by alterations in regulating critical genes involved in this healing process. Unfortunately, the elderly are particularly susceptible to hip bone fractures, which pose a significant burden associated with higher morbidity and mortality rates. A notable change in older adults is the increased expression of activation, adhesion, and migration markers in circulating monocytes. However, there is a decrease in the expression of co-inhibitory molecules. Recently, research evidence has shown that the migration of specific monocyte subsets to the site of hip fracture plays a crucial role in bone resorption and remodeling, especially concerning age-related factors. In this review, we summarize the current knowledge about uniqueness characteristics of monocytes, and their potential regulation and moderation to enhance the healing process of hip fractures. This breakthrough could significantly contribute to the comprehension of aging process at a fundamental aging mechanism through this initiative would represent a crucial stride for diagnosing and treating age related hip fracture. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) emerges as a severe crisis to public health and requires global action. The occurrence of bacterial pathogens with multi‐drug resistance appeals to exploring alternative therapeutic strategies. Antivirulence treatment has been a positive substitute in seeking to circumvent AMR, which aims to target virulence factors directly to combat bacterial infections. Accumulated evidence suggests that plant‐derived natural products, which have been utilized to treat infectious diseases for centuries, can be abundant sources for screening potential virulence‐arresting drugs (VADs) to develop advanced therapeutics for infectious diseases. This review sums up some virulence factors and their actions in various species of bacteria, as well as recent advances pertaining to plant‐derived natural products as VAD candidates. Furthermore, we also discuss natural VAD‐related clinical trials and patents, the perspective of VAD‐based advanced therapeutics for infectious diseases and critical challenges hampering clinical use of VADs, and genomics‐guided identification for VAD therapeutic. These newly discovered natural VADs will be encouraging and optimistic candidates that may sustainably combat AMR. [ABSTRACT FROM AUTHOR]

Diet is currently recognized as a major modifiable agent of human health. In particular, dietary nitrate has been increasingly explored as a strategy to modulate different physiological mechanisms with demonstrated benefits in multiple organs, including gastrointestinal, cardiovascular, metabolic, and endocrine systems. An intriguing exception in this scenario has been the brain, for which the evidence of the nitrate benefits remains controversial. Upon consumption, nitrate can undergo sequential reduction reactions in vivo to produce nitric oxide (*NO), a ubiquitous paracrine messenger that supports multiple physiological events such as vasodilation and neuromodulation. In the brain, *NO plays a key role in neurovascular coupling, a fine process associated with the dynamic regulation of cerebral blood flow matching the metabolic needs of neurons and crucial for sustaining brain function. Neurovascular coupling dysregulation has been associated with neurodegeneration and cognitive dysfunction during different pathological conditions and aging. We discuss the potential biological action of nitrate on brain health, concerning the molecular mechanisms underpinning this association, particularly via modulation of *NO-dependent neurovascular coupling. The impact of nitrate supplementation on cognitive performance was scrutinized through preclinical and clinical data, suggesting that intervention length and the health condition of the participants are determinants of the outcome. Also, it stresses the need for multimodal quantitative studies relating cellular and mechanistic approaches to function coupled with behavior clinical outputs to understand whether a mechanistic relationship between dietary nitrate and cognitive health is operative in the brain. If proven, it supports the exciting hypothesis of cognitive enhancement via diet. [ABSTRACT FROM AUTHOR]

Taking the visual perspective of another individual is an important skill in social communication, and is termed visual perspective-taking (VPT). Individuals with autism spectrum disorder who have deficits in social interaction show relatively lower performance on VPT tasks than individuals who achieve age-appropriate developmental milestones. Thus, researchers have attempted to teach VPT skills and component behaviors to children with autism spectrum disorder. This pilot study evaluated the effects of a technology-based intervention on VPT skills in an adolescent male with autism spectrum disorder and moderate intellectual disabilities using a multiple-probe across behaviors design. Using a training package composed of multi-view videos with feedback, we trained the participant to discriminate whether the experimenter could see an object and to discriminate between right or left based on the experimenter's perspective. The results showed that the percentage of correct responses for each skill increased when the training package was applied. Furthermore, we observed generalization of VPT skills to untrained lab and natural environment settings. We discussed (1) the possibility that training multiple exemplars resulted in broad generalization, (2) the effectiveness of experiencing other people's perspectives when training VPT skills, and (3) the potential and limitations of multi-view videos for clinical application based on the results of the social validity questionnaire. [ABSTRACT FROM AUTHOR]

Enhancing electronic transport properties of thermoelectric oxides is of great technological importance. Oxides are promising candidates for waste heat harvesting at elevated temperatures as well as for electricity generation in low‐power applications. To this purpose, fundamental understanding of their electrical and thermal conduction mechanisms is essential. Herein, the conduction mechanism of CaMnO3 materials is focused on and how dopant identity and amount alter the kinetic properties of charge transport is investigated. Ca1−xRxMnO3 compounds with R = Y and La are synthesized, where 0 ≤ x ≤ 0.13, and the electrical conductivity and Seebeck coefficient for temperatures ranging from 300 to 1050 K, indicating that Y‐doped compounds are usually more conductive than their La‐doped counterparts, are measured. Analysis of both in terms of the small polaron hopping model reveals that Y doping reduces conduction activation energies, resulting in higher electrical conductivity and charge carrier mobility. Remarkably high values of thermoelectric power factor for the Ca0.97La0.03MnO3 compound, for example, 300 μWm−1 K−2 at 1050 K are observed; furthermore, these values are preserved for a wide temperature range, rendering this compound a good candidate for heat‐to‐electrical power generation at elevated temperatures. [ABSTRACT FROM AUTHOR]

Purpose: The airway defense mechanism of cough is essential for human survival. Recognition is growing about the distinct role of speech-language pathologists in the nonpharmacological management of various cough disorders. This clinical focus article aims to deliver relevant education about normal and pathological cough to strengthen existing clinical knowledge and skills. Conclusions: The neuronal pathways underlying normal cough function are complex. Cough problems refer to either reduced or heightened cough stemming from various disease processes, and both clinical presentations have detrimental consequences. Current evidence supports that patients who suffer from cough dysfunction benefit from nonpharmacological interventions offered via speech therapy as an adjunct to medical treatments. Speech therapy strategies apply the higher cognitive components of cough by focusing on the deliberate modification and coordination of respiration. Future research priorities are positioned toward improving clinical outcomes for cough disorders. [ABSTRACT FROM AUTHOR]

Fourteen kilograms of minced meat were divided into 4 groups (about 3.5 Kg for each group). All samples were examined to study the effect of the addition of 1% fruit peel extracts (banana, orange, and pomegranate) on the extension of the shelf life of such food article. Reduction of APC after 6 days in samples treated with banana, orange, and pomegranate peel reached 83.9 %, 91.6 %, and 95.4%, respectively and reduction of articles coliform reached 75.8%, 90.3 %, and 93% while S. aureus count reduced by 77.5%, 89%, and 96.5 %, respectively. Fruit peels decreased pH values compared with the control sample during storage at 4°C for 10 days. pH values of samples treated with banana peel decreased from 5.63 to 5.61 at zero time and from 6.71 to 5.84 on the 6th day and orange peel decreased to 5.58 and to 5.70 while pomegranate to 5.56 and to 5.67 at zero time and on the 6th day of storage, respectively. TVB-N values of samples treated with banana decreased from 1.97 to 1.89 at zero time and from 29.58 to 9.83 on the 6th day and orange peel decreased to 1.84 and to 7.90 while pomegranate to 1.81 and to 6.88 at zero time and on the 6th day. TBA values of samples treated with banana peel decreased from 1.22 to 0.25 on the 6th day but orange peel decreased to 0.02 and to 0.19 and with pomegranate to 0.02 and to 0.14 at zero time and on the 6th day of storage, respectively. In general, the incorporation of banana, orange, and pomegranate peel powder into minced meat as natural preservatives improved color, odor, appearance, consistency, and overall acceptability and extended their shelf life during storage. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR)-associated vision loss is a devastating disease affecting the working-age population. Retinal pathology is due to leakage of serum components into retinal tissues, activation of resident phagocytes (microglia), and vascular and neuronal damage. While short-term interventions are available, they do not revert visual function or halt disease progression. The impact of microglial inflammatory responses on the neurovascular unit remains unknown. In this study, we characterized microglia–vascular interactions in an experimental model of DR. Early diabetes presents activated retinal microglia, vascular permeability, and vascular abnormalities coupled with vascular tortuosity and diminished astrocyte and endothelial cell-associated tight-junction (TJ) and gap-junction (GJ) proteins. Microglia exclusively bind to the neuronal-derived chemokine fractalkine (FKN) via the CX3CR1 receptor to ameliorate microglial activation. Using neuron-specific recombinant adeno-associated viruses (rAAVs), we therapeutically overexpressed soluble (sFKN) or membrane-bound (mFKN) FKN using intra-vitreal delivery at the onset of diabetes. This study highlights the neuroprotective role of rAAV-sFKN, reducing microglial activation, vascular tortuosity, fibrin(ogen) deposition, and astrogliosis and supporting the maintenance of the GJ connexin-43 (Cx43) and TJ zonula occludens-1 (ZO-1) molecules. The results also show that microglia–vascular interactions influence the vascular width upon administration of rAAV-sFKN and rAAV-mFKN. Administration of rAAV-sFKN improved visual function without affecting peripheral immune responses. These findings suggest that overexpression of rAAV-sFKN can mitigate vascular abnormalities by promoting glia–neural signaling. sFKN gene therapy is a promising translational approach to reverse vision loss driven by vascular dysfunction. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal (GI) complications in lung transplant recipients can occur any time during the post‐operative period, leading to prolonged morbidity and mortality. Despite the negative association between GI complications and patient outcomes, little is known about their incidence and risk factors for their development in pediatric lung transplant recipients. Methods: We performed a retrospective chart review at one pediatric tertiary center to describe the frequency of GI complications in lung transplant recipients. We identified potential risk factors for the diagnosis of gastroparesis, gastroesophageal reflux disease (GERD) and aspiration in the post‐transplant period. Lastly, we investigated the association of these complications with mortality and graft survival. Results: 84.3% of lung transplant recipients experienced at least one GI complication in the post‐transplant period. Gastroparesis (52.9%), GERD (41.2%), and oropharyngeal dysphagia/laryngeal penetration (33.3%) were the most common complications diagnosed. Post‐operative opioid exposure was a risk factor for gastroparesis, with the odds increasing 3.0% each day a patient was prescribed opioids (p =.021). The risk of death or retransplant in individuals who experienced gastroparesis was 2.7 times higher than those not diagnosed with gastroparesis (p =.027). Conclusion: Exposure to opioids in the post‐operative period is a risk factor for gastroparesis and a prolonged hospitalization placed patients at risk for aspiration. Gastroparesis was associated with increased patient mortality and graft failure, while aspiration and GERD had no effect on long term outcomes. Future prospective studies investigating the relationship between opioid use and the development of a gastroparesis are necessary to improve patient outcomes. [ABSTRACT FROM AUTHOR]