Diagnostic performance of tomosynthesis plus synthetic mammography versus full-field digital mammography with or without tomosynthesis in breast cancer screening: A systematic review and meta-analysis.

Digital breast tomosynthesis (DBT) with full-field digital mammography (FFDM) exposes women to a higher radiation dose. A synthetic 2D mammogram (S2D) is a two-dimensional image constructed from DBT. We aim to evaluate the S2D performance when used alone or combined with DBT compared to FFDM alone or with DBT. Studies were included if they recruited screening participants and reported on S2D performance. Studies were excluded if they included symptomatic patients, imaging was for diagnostic purposes, or if participants had a breast cancer history. Meta-analyses for cancer detection rates (CDR) and Specificities were conducted where available. Differences in the performance of imaging modalities were calculated within individual studies, and these were pooled by meta-analysis. Out of 3241 records identified, 17 studies were included in the review and 13 in the meta-analysis. The estimated combined difference in CDRs per thousand among individual studies that reported on DBT plus S2D vs. FFDM and those reporting on DBT plus S2D versus DBT plus FFDM was 2.03 (95% CI 0.81-3.25) and - 0.15 (95% CI -1.17 to 0.86), respectively. The estimated difference in percent specificities was 1.13 (95% CI -0.06 to 2.31) in studies comparing DBT plus S2D and FFDM. In studies comparing DBT plus S2D and DBT plus FFDM, the estimated difference in specificities was 1.08 (95% CI 0.59-1.56). DBT plus S2D showed comparable accuracy to FFDM plus DPT and improved cancer detection to FFDM alone. Integrating S2D with DBT in breast cancer screening is safe and preserves performance.

Systematic characterization of Gossypium GLN family genes reveals a potential function of GhGLN1.1a regulates nitrogen use efficiency in cotton.

The enzyme glutamine synthetase (GLN) is mainly responsible for the assimilation and reassimilation of nitrogen (N) in higher plants. Although the GLN gene has been identified in various plants, there is little information about the GLN family in cotton (Gossypium spp.). To elucidate the roles of GLN genes in cotton, we systematically investigated and characterized the GLN gene family across four cotton species (G. raimondii, G. arboreum, G. hirsutum, and G. barbadense). Our analysis encompassed analysis of members, gene structure, cis-element, intragenomic duplication, and exploration of collinear relationships. Gene duplication analysis indicated that segmental duplication was the primary driving force for the expansion of the GhGLN gene family. Transcriptomic and quantitative real-time reverse-transcription PCR (qRT-PCR) analyses indicated that the GhGLN1.1a gene is responsive to N induction treatment and several abiotic stresses. The results of virus-induced gene silencing revealed that the accumulation and N use efficiency (NUE) of cotton were affected by the inactivation of GhGLN1.1a. This study comprehensively analyzed the GhGLN genes in Gossypium spp., and provides a new perspective on the functional roles of GhGLN1.1a in regulating NUE in cotton.

A reverse translational approach reveals the protective roles of Mangifera indica in inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.

S100A8/A9 drives the formation of procoagulant platelets through GPIbα.

S100A8/A9, also known as "calprotectin" or "MRP8/14," is an alarmin primarily secreted by activated myeloid cells with antimicrobial, proinflammatory, and prothrombotic properties. Increased plasma levels of S100A8/A9 in thrombo-inflammatory diseases are associated with thrombotic complications. We assessed the presence of S100A8/A9 in the plasma and lung autopsies from patients with COVID-19 and investigated the molecular mechanism by which S100A8/A9 affects platelet function and thrombosis. S100A8/A9 plasma levels were increased in patients with COVID-19 and sustained high levels during hospitalization correlated with poor outcomes. Heterodimeric S100A8/A9 was mainly detected in neutrophils and deposited on the vessel wall in COVID-19 lung autopsies. Immobilization of S100A8/A9 with collagen accelerated the formation of a fibrin-rich network after perfusion of recalcified blood at venous shear. In vitro, platelets adhered and partially spread on S100A8/A9, leading to the formation of distinct populations of either P-selectin or phosphatidylserine (PS)-positive platelets. By using washed platelets, soluble S100A8/A9 induced PS exposure but failed to induce platelet aggregation, despite GPIIb/IIIa activation and alpha-granule secretion. We identified GPIbα as the receptor for S100A8/A9 on platelets inducing the formation of procoagulant platelets with a supporting role for CD36. The effect of S100A8/A9 on platelets was abolished by recombinant GPIbα ectodomain, platelets from a patient with Bernard-Soulier syndrome with GPIb-IX-V deficiency, and platelets from mice deficient in the extracellular domain of GPIbα. We identified the S100A8/A9-GPIbα axis as a novel targetable prothrombotic pathway inducing procoagulant platelets and fibrin formation, in particular in diseases associated with high levels of S100A8/A9, such as COVID-19.

C2 Product Formation over the C1 Product and HER on the 111 Plane of Specific Cu Alloy Nanoparticles Identified through Multiparameter Optimization.

C2 products are more desirable than C1 products during CO2 electroreduction (CO2ER) because the former possess higher energy density and greater industrial value. For CO2ER, Cu is a well-known catalyst, but the selectivity toward C2 products is still a big challenge for researchers due to complex intermediates, different final products, and large space of the catalyst due to its morphology, plane, size, host surface etc. Using density functional theory (DFT) calculations, we find that alloying of Cu nanoparticles can help to enhance the selectivity toward C2 products during CO2ER with a low overpotential. By a systematic investigation of 111 planes (which prefer the C1 product in the case of bulk Cu), the alloys show the generation of C2 products via *CO-*CO dimerization (* indicates adsorbed state). It also suppresses the counter-pathway of hydrogenation of *CO to *CHO, which leads to C1 products. Further, we find that *CH2CHO is the bifurcating intermediate to distinguish between ethanol and ethylene as the final product. We have used simple graphical construction to identify the catalyst for CO2ER over HER, and vice versa. We have also defined the case of hydrogen poisoning and projected a parity plot to recognize the catalyst for C2 product evolution over the C1 product. Our study reveals that Cu-Ag and Cu-Zn catalysts selectively promote ethanol production on 111 planes. Moreover, an edge-doped 2SO2 graphene nanoribbon as the host layer further lowers the barrier and selectively promotes ethanol on Cu38- and Cu79-based alloys. This work provides new theoretical insights into designing Cu-based nanoalloy catalysts for C2 product formation on the 111 plane.

Empirical analysis of cost-effective and equitable solid waste management systems: Environmental and economic perspectives.

The solid waste management (SWM) system is in a transitional phase in developing economies, and local municipalities and waste management companies are stepping toward integrating a waste treatment approach in the scheme of waste handling. However, there is an urgent need to explore cost-effective techniques, models, and potential revenue streams to sustain the state-run waste sector self-sufficiently. The proposed SWM model aims to support the local waste sector in Islamabad, the capital city of Pakistan, with 100% service area coverage to attain environmental and economic sustainability by defining dedicated waste collection streams to ensure quality material recovery under a cost-effective approach and modality. The innovative approach is applied to allocate the tonnage to various streams as per the city's current land use plan. The estimated/cost of the cleanliness services will be USD13.1 million per annum with an estimated per ton cost of USD 23. The establishment of the proposed material recovery facility (MRF) will process about 500 t/d of waste to produce 45 t/d compost and recover 130 t/d of recyclables. The environmentally friendly model saves 2.4 million tons of CO2‒eq/month from composting and recycling. The average economic potential from MRF and debris-crushing plants, including environmental benefit value, is calculated as USD 3.97 million annually. Recovery of services fee (70%) for various collection streams based on city land use and socio-economic conditions will generate revenue of USD 7.33 million annually. The total revenue will be USD 11.31 million (86% of total annual expenditures) to track the sector's self-sufficiency. To successfully reach the Sustainable Development Goals (SDGs) and Nationally Determined Contributions (NDCs), engaging the private sector from environmentally advanced economies to collaborate in the waste sector to enhance local technical capabilities is recommended.

The central and peripheral corneal response to short-term hypoxia.

PURPOSE: To quantify the magnitude and recovery of central and limbal corneal oedema induced by short-term unilateral eyelid closure without contact lens wear. METHODS: The left eye of 10 adults with healthy corneas was patched using a folded eye pad for 30 min. High-resolution optical coherence tomography images (which captured the limbal and central corneal regions simultaneously) were obtained before patching, immediately after eye opening and again at 1, 2, 5, 6, 9, 10, 14 and 15 mins after eyelid opening. Oedema was measured from the limbus (scleral spur) to the central cornea (thinnest corneal location) along the horizontal meridian. RESULTS: A greater amount of limbal oedema was noted (mean [SD] 3.84 [1.79] %) compared to the central cornea (2.48 [0.61] %; p = 0.04) after 30 mins of unilateral eyelid closure. Both central and limbal corneal oedema recovered rapidly following eyelid opening, with no significant differences in the rate of corneal recovery between corneal locations (p = 0.90). CONCLUSIONS: Short-term unilateral eyelid closure resulted in ~55% more relative oedema in the limbal region compared to the central cornea. Rapid recovery of oedema and corneal overshoot (thinning beyond the baseline corneal thickness) was observed within 1-2 min of eyelid opening for both central and peripheral regions.

Alternative Approaches for the Management of Urinary Tract Infection with Crano-cure: A Randomized Clinical Trial.

Background: Urinary tract infection (UTI) is a renal infection that affects the urinary tract and is global problem related to health and many people are affected each year at some points of their lives. Modern studies about urinary tract infections show that almost one third of the world's population has been suffering from this ailment. Different antibacterial medicines have been reported to have resistance against pathogens. In order to overcome the problem, exploration for new and dynamic antibacterial agents from natural sources is the emerging trend. Primary Study Objective: The primary objective was to evaluate the efficacy and safety of the polyherbal test drug formulation, "Crano-cure", as treatment for UTIs. Methods/Design: In the current study, clinical trials were designed to evaluate the effects of the polyherbal formulation "Crano-cure" compared to the standard drug Ciprofloxacin in randomized, controlled multicenter trial of 205 patients, analyzing clinical outcomes and safety profiles. Setting and Participants: Conducted across multiple centers, including Shifa-ul-Mulk Memorial Hospital at Hamdard University Karachi and three other clinics, the study involved 205 patients aged 15-60, irrespective of their socioeconomic status. Intervention: Patients were classified into two groups i.e. control group (ciprofloxacin) and the test group (crane-cure). Polyherbal formulation of 500 mg Crano-cure capsules two times in a day were administered to the test group for 28 days. The control group was administered a control ciprofloxacin tablet 500 mg two times in a day for 28 days. Primary Outcome Measures: The drug was found safe for further clinical study after observing changes or improvements in UTI symptoms, urine culture and blood complete tests. The clinical trial was dully registered on the US National Library of Medicine, ClinicalTrials.gov Identifier: NCT04575493. The trial was accompanied in the instructions of EC (Ethical Committee). The study plan and procedures were displayed to the BASR (Board of Advance Studies and Research) and board members of the Ethical Committee (EC), which was ERB-2021-9-1. Results: Clinical study results revealed the effectiveness of Crano-cure in the management of UTIs symptoms and hematological and biochemical parameters including blood complete test, liver function tests, renal function tests and lipid profile. Moreover, the test drug Crano-cure revealed a significance level (P ≤ .05) in compliance and cost-effectiveness compared to control ciprofloxacin. Conclusion: In conclusion, Crano-cure is a safe and cost-effective alternate to Ciprofloxacin for treatment of UTIs.

Time to consider blunt needles for implant surgery? A systematic review and meta-analysis shows that blunt suture needles reduce glove perforation.

BACKGROUND: Despite a recent Cochrane Review demonstrating blunt suture needles are safer for surgeons, the use of blunt suture needles has not become widely adopted. In the 'Implant Era', with the value of medical implant companies to surpass $145 billion by 2027, should we re-examine the use of blunt suture needles, especially to reduce infection in implant surgery? We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing whether blunt suture needles reduce risks to surgeons and patients. METHODS: A systematic review and meta-analysis was performed per PRISMA guidelines. PubMed, Cochrane and EMBASE databases were searched for RCTs. Dichotomous variables were pooled as risk ratios (RR) and associated 95% confidence intervals (CI) using the MH method. Random or fixed effects modelling use was based on statistical heterogeneity (I2). RESULTS: 14 RCTs were identified with 2488 patients. The RCTs included laparotomies, caesarean sections, episiotomies, and orthopaedic surgeries. Blunt suture needles when compared with sharp needles resulted in a significant reduction in glove perforation; RR: 0.47, 95% CI [0.37 to 0.60] and needlestick injuries, RR: 0.50, 95% CI [0.26 to 0.97]. Sharp needles caused more wound infections, but the result was not statistically significant; RR: 2.73, 95% CI [0.54 to 13.76], p 0.22. Surgeon's satisfaction decreased with blunt needles compared with sharp (RR: 1.22, 95% CI [1.09 to 1.37]). CONCLUSION: Blunt suture needles are safer than sharp needles for surgeons and likely reduce risks to patients. This, however, comes at the cost of decreased ease of use. The authors recommend the routine use of blunt suture needles, especially in implant surgery.

Particulate matter retention and removal efficiency in ten tree species of semi-arid environment.

Modern era has witnessed particulate matter (PM) become one of the biggest threats for the existence of biological species. Therefore, a study was performed in Faisalabad city to evaluate PM retention and removal efficiency of ten local tree species. Branch samples were collected from urban, sub-urban and rural areas in September 2020 (183 days after rain), and in August 2021 (30 days after rain). Results showed that total PM load, PM>10 and PM10-2.5 retention was the highest in urban followed by sub-urban and rural area. PM>10, PM10-2.5, total PM, and PM deposition rate decreased significantly in the following order, F. benghalensis > T. arjuna > S. cumini > A. scholaris > F. religiosa > E. camaldulensis > D sissoo > C lancifolius > B. ceiba > M. alba during both years 2020, and 2021. During the artificial rainfall experiment, total PM removed by the species also followed the same order however, PM removal efficiency was the highest in B. ceiba and M. alba followed by E. camaldulensis, C. lancifolius, D. sissoo, T. arjuna, S. cumini, A. scholaris, F. religiosa and F. benghalensis. Therefore, it can be concluded that species selection must be done skillfully for congested urban environment.

Owing to excessive industrialization and motorization, optimizing particulate matter (PM) removal from the atmosphere has become imperative. Since, trees can help in controlling the atmospheric PM therefore, current study aimed to evaluate the efficiency of ten tree species in controlling the atmospheric PM. These species belong to arid and semi-arid regions have not been characterized for the efficiency in removing PM from the atmosphere. The results will help in the selection of efficient local tree species for controlling atmospheric PM especially in the congested urban environment.

Transcription Factor PecS Mediates Agrobacterium fabrum Fitness and Survival.

The transcriptional regulator PecS is encoded by select bacterial pathogens. For instance, in the plant pathogen Dickeya dadantii, PecS controls a range of virulence genes, including pectinase genes and the divergently oriented gene pecM, which encodes an efflux pump through which the antioxidant indigoidine is exported. In the plant pathogen Agrobacterium fabrum (formerly named Agrobacterium tumefaciens), the pecS-pecM locus is conserved. Using a strain of A. fabrum in which pecS has been disrupted, we show here that PecS controls a range of phenotypes that are associated with bacterial fitness. PecS represses flagellar motility and chemotaxis, which are processes that are important for A. fabrum to reach plant wound sites. Biofilm formation and microaerobic survival are reduced in the pecS disruption strain, whereas the production of acyl homoserine lactone (AHL) and resistance to reactive oxygen species (ROS) are increased when pecS is disrupted. AHL production and resistance to ROS are expected to be particularly relevant in the host environment. We also show that PecS does not participate in the induction of vir genes. The inducing ligands for PecS, urate, and xanthine, may be found in the rhizosphere, and they accumulate within the plant host upon infection. Therefore, our data suggest that PecS mediates A. fabrum fitness during its transition from the rhizosphere to the host plant. IMPORTANCE PecS is a transcription factor that is conserved in several pathogenic bacteria, where it regulates virulence genes. The plant pathogen Agrobacterium fabrum is important not only for its induction of crown galls in susceptible plants but also for its role as a tool in the genetic manipulation of host plants. We show here that A. fabrum PecS controls a range of phenotypes, which would confer the bacteria an advantage while transitioning from the rhizosphere to the host plant. This includes the production of signaling molecules, which are critical for the propagation of the tumor-inducing plasmid. A more complete understanding of the infection process may inform approaches by which to treat infections as well as to facilitate the transformation of recalcitrant plant species.

Phosphorus and carbohydrate metabolism contributes to low phosphorus tolerance in cotton.

Low phosphorus (P) is one of the limiting factors in sustainable cotton production. However, little is known about the performance of contrasting low P tolerant cotton genotypes that might be a possible option to grow in low P condition. In the current study, we characterized the response of two cotton genotypes, Jimian169 a strong low P tolerant, and DES926 a weak low P tolerant genotypes under low and normal P conditions. The results showed that low P greatly inhibited growth, dry matter production, photosynthesis, and enzymatic activities related to antioxidant system and carbohydrate metabolism and the inhibition was more in DES926 as compared to Jimian169. In contrast, low P improved root morphology, carbohydrate accumulation, and P metabolism, especially in Jimian169, whereas the opposite responses were observed for DES926. The strong low P tolerance in Jimian169 is linked with a better root system and enhanced P and carbohydrate metabolism, suggesting that Jimian169 is a model genotype for cotton breeding. Results thus indicate that the Jimian169, compared with DES926, tolerates low P by enhancing carbohydrate metabolism and by inducing the activity of several enzymes related to P metabolism. This apparently causes rapid P turnover and enables the Jimian169 to use P more efficiently. Moreover, the transcript level of the key genes could provide useful information to study the molecular mechanism of low P tolerance in cotton.

Differential responses of contrasting low phosphorus tolerant cotton genotypes under low phosphorus and drought stress.

BACKGROUND: Drought is one of the main reasons for low phosphorus (P) solubility and availability. AIMS: The use of low P tolerant cotton genotypes might be a possible option to grow in drought conditions. METHODS: This study investigates the tolerance to drought stress in contrasting low P-tolerant cotton genotypes (Jimian169; strong tolerant to low P and DES926; weak tolerant to low P). In hydroponic culture, the drought was artificially induced with 10% PEG in both cotton genotypes followed by low (0.01 mM KH2PO4) and normal (1 mM KH2PO4) P application. RESULTS: The results showed that under low P, PEG-induced drought greatly inhibited growth, dry matter production, photosynthesis, P use efficiency, and led to oxidative stress from excessive malondialdehyde (MDA) and higher accumulation of reactive oxygen species (ROS), and these effects were more in DES926 than Jimian169. Moreover, Jimian169 alleviated oxidative damage by improving the antioxidant system, photosynthetic activities, and an increase in the levels of osmoprotectants like free amino acids, total soluble proteins, total soluble sugars, and proline. CONCLUSIONS: The present study suggests that the low P-tolerant cotton genotype can tolerate drought conditions through high photosynthesis, antioxidant capacity, and osmotic adjustment.

PEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation.

Dysregulation of leukocyte trafficking, lipid metabolism, and other metabolic processes are the hallmarks that underpin and drive pathology in obesity. Current clinical management targets alternations in lifestyle choices (e.g. exercise, weight loss) to limit the impact of the disease. Crucially, re-gaining control over the pathogenic cellular and molecular processes may offer an alternative, complementary strategy for obese patients. Here we investigate the impact of the immunopeptide, PEPITEM, on pancreas homeostasis and leukocyte trafficking in mice on high-fed obesogenic diet (HFD). Both prophylactic and therapeutic treatment with PEPITEM alleviated the effects of HFD on the pancreas, reducing pancreatic beta cell size. Moreover, PEPITEM treatment also limited T-cell trafficking (CD4+ T-cells and KLRG1+ CD3+ T-cells) to obese visceral, but not subcutaneous, adipose tissue. Similarly, PEPITEM treatment reduced macrophage numbers within the peritoneal cavity of mice on HFD diet at both 6 and 12 weeks. By contrast, PEPITEM therapy elevated numbers of T and B cells were observed in the secondary lymphoid tissues (e.g. spleen and inguinal lymph node) when compared to the untreated HFD controls. Collectively our data highlights the potential for PEPITEM as a novel therapy to combat the systemic low-grade inflammation experienced in obesity and minimize the impact of obesity on pancreatic homeostasis. Thus, offering an alternative strategy to reduce the risk of developing obesity-related co-morbidities, such as type 2 diabetes mellitus, in individuals at high risk and struggling to control their weight through lifestyle modifications.

New biologic (Ab-IPL-IL-17) for IL-17-mediated diseases: identification of the bioactive sequence (nIL-17) for IL-17A/F function.

OBJECTIVES: Interleukin (IL) 17s cytokines are key drivers of inflammation that are functionally dysregulated in several human immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). Targeting these cytokines has some therapeutic benefits, but issues associated with low therapeutic efficacy and immunogenicity for subgroups of patients or IMIDs reduce their clinical use. Therefore, there is an urgent need to improve the coverage and efficacy of antibodies targeting IL-17A and/or IL-17F and IL-17A/F heterodimer. METHODS AND RESULTS: Here, we initially identified a bioactive 20 amino acid IL-17A/F-derived peptide (nIL-17) that mimics the pro-inflammatory actions of the full-length proteins. Subsequently, we generated a novel anti-IL-17 neutralising monoclonal antibody (Ab-IPL-IL-17) capable of effectively reversing the pro-inflammatory, pro-migratory actions of both nIL-17 and IL-17A/F. Importantly, we demonstrated that Ab-IPL-IL-17 has less off-target effects than the current gold-standard biologic, secukinumab. Finally, we compared the therapeutic efficacy of Ab-IPL-IL-17 with reference anti-IL-17 antibodies in preclinical murine models and samples from patients with RA and IBD. We found that Ab-IPL-IL-17 could effectively reduce clinical signs of arthritis and neutralise elevated IL-17 levels in IBD patient serum. CONCLUSIONS: Collectively, our preclinical and in vitro clinical evidence indicates high efficacy and therapeutic potency of Ab-IPL-IL-17, supporting the rationale for large-scale clinical evaluation of Ab-IPL-IL-17 in patients with IMIDs.

Galectin-9 mediates neutrophil capture and adhesion in a CD44 and ß2 integrin-dependent manner.

Neutrophil trafficking is a key component of the inflammatory response. Here, we have investigated the role of the immunomodulatory lectin Galectin-9 (Gal-9) on neutrophil recruitment. Our data indicate that Gal-9 is upregulated in the inflamed vasculature of RA synovial biopsies and report the release of Gal-9 into the extracellular environment following endothelial cell activation. siRNA knockdown of endothelial Gal-9 resulted in reduced neutrophil adhesion and neutrophil recruitment was significantly reduced in Gal-9 knockout mice in a model of zymosan-induced peritonitis. We also provide evidence for Gal-9 binding sites on human neutrophils; Gal-9 binding induced neutrophil activation (increased expression of ß2 integrins and reduced expression of CD62L). Intra-vital microscopy confirmed a pro-recruitment role for Gal-9, with increased numbers of transmigrated neutrophils following Gal-9 administration. We studied the role of both soluble and immobilized Gal-9 on human neutrophil recruitment. Soluble Gal-9 significantly strengthened the interaction between neutrophils and the endothelium and inhibited neutrophil crawling on ICAM-1. When immobilized, Gal-9 functioned as an adhesion molecule and captured neutrophils from the flow. Neutrophils adherent to Gal-9 exhibited a spread/activated phenotype that was inhibited by CD18 and CD44 neutralizing antibodies, suggesting a role for these molecules in the pro-adhesive effects of Gal-9. Our data indicate that Gal-9 is expressed and released by the activated endothelium and functions both in soluble form and when immobilized as a neutrophil adhesion molecule. This study paves the way for further investigation of the role of Gal-9 in leukocyte recruitment in different inflammatory settings.

Interleukin-17 (IL-17) triggers systemic inflammation, peripheral vascular dysfunction, and related prothrombotic state in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most prevalent forms of neurodegenerative disorders. Previously, we have shown that in vivo administration of an IL-17 neutralizing antibody (IL-17Ab) rescues amyloid-ß-induced neuro-inflammation and memory impairment, demonstrating the pivotal role of IL-17 in AD-derived cognitive deficit. Recently, AD has been recognized as a more intriguing pathology affecting vascular networks and platelet function. However, not much is known about peripheral vascular inflammation and how pro-inflammatory circulating cells/mediators could affect peripheral vessels' function. This study aimed to evaluate whether IL-17Ab treatment could also impact peripheral AD features, such as systemic inflammation, peripheral vascular dysfunction, and related pro-thrombotic state in a non-genetic mouse model of AD. Mice were injected intracerebroventricularly with Aß1-42 peptide (3 µg/3 µl). To evaluate the systemic/peripheral protective profile of IL-17Ab, we used an intranasal administration of IL-17Ab (1 µg/10 µl) at 5, 12, and 19 days after Aß1-42 injection. Circulating Th17/Treg cells and related cyto-chemokines, haematological parameters, vascular/endothelial reactivity, platelets and coagulation function in mice were evaluated. IL-17Ab treatment ameliorates the systemic/peripheral inflammation, immunological perturbance, vascular/endothelial impairment and pro-thrombotic state, suggesting a key role for this cytokine in fostering inflammatory processes that characterize the multifaced aspects of AD.

Central and peripheral scleral lens-induced corneal oedema.

PURPOSE: To quantify the magnitude of central and peripheral scleral lens-induced corneal oedema for a range of fluid reservoir thicknesses, and to compare these experimental results with theoretical models of corneal oedema both with and without limbal metabolic support (i.e., the lateral transport of metabolites and the influence of the limbal vasculature). METHODS: Ten young healthy participants wore scleral lenses (KATT™, Capricornia Contact Lenses) fitted with low (mean 141 µm), medium (482 µm) and high (718 µm) central fluid reservoir thickness values across three separate study visits. The scleral lens thickness, fluid reservoir thickness and stromal corneal oedema were measured using optical coherence tomography. Oedema was quantified across the central (0-2.5 mm from the corneal apex) and peripheral (1.25-3 mm from the scleral spur) cornea. Experimental data were compared with published theoretical models of central to peripheral corneal oedema. RESULTS: Stromal oedema varied with fluid reservoir thickness (p < 0.001) for both central and peripheral regions. The mean (standard deviation) stromal oedema was greater for the medium (2.08 (1.21)%) and high (2.22 (1.31)%) fluid reservoir thickness conditions compared to the low condition (1.00 (1.01)%) (p ≤ 0.01). Stromal oedema gradually increased from the corneal centre to the periphery by ~0.3% on average (relative increase of 18%), but the change did not reach statistical significance. This trend of increasing, rather than decreasing, oedema towards the limbus is consistent with theoretical modelling of peripheral oedema without metabolic support from the limbus. CONCLUSIONS: The central and peripheral cornea displayed a similar magnitude of oedema, with increasing levels observed for medium and high fluid reservoir thicknesses. The gradual increase in oedema towards the limbus is consistent with a 'without limbal metabolic support' theoretical model.

Impact of Scleral Lens Front Surface Eccentricity on Visual Acuity, Contrast Sensitivity, and Higher-Order Aberrations in Eyes With Keratoconus.

PURPOSE: To investigate the effect of front surface eccentricity (FSE) of scleral lenses (SLs) on corrected distance visual acuity (CDVA), contrast sensitivity (CS), and higher-order aberrations (HOAs) in keratoconic eyes. METHODS: Fifteen keratoconic eyes fitted with BostonSight SCLERAL lenses of different eccentricity values (FSE0=0, FSE1=0.30, and FSE2=0.60). CDVA, CS, and HOAs were measured at baseline and after 30 min of SL wear. CDVA and CS were measured with the Early Treatment Diabetic Retinopathy Study and Pelli-Robson chart, respectively, and iTrace aberrometer was used to evaluate the HOAs. RESULTS: Baseline CDVA was 0.30±0.29, which significantly improved to 0.10±0.11, 0.05±0.06, and 0.05±0.08 logMAR with FSE0, FSE1, and FSE2, respectively ( P <0.05). The post hoc showed no significant difference between eccentricities. Baseline CS was 1.19±0.47, which improved to 1.54±0.12, 1.59±0.10, and 1.60±0.11 with FSE0, FSE1, and FSE2, respectively ( P <0.01), but post hoc showed no significant difference between eccentricities. A statistically significant reduction was found in HOAs when compared with baseline ( P <0.01). Comparison between eccentricities showed a significant difference only between FSE0 and FSE1 for RMS coma ( P =0.01) and RMS spherical aberrations ( P =0.004) where FSE1 showed better performance in reducing HOAs compared with FSE0. HO-RMS, RMS secondary astigmatism, and RMS trefoil showed no significant difference between eccentricities, but FSE1 and FSE2 performed superior to FSE0. CONCLUSION: BostonSight SCLERAL lenses with varying eccentricities corrected a significant amount of HOAs and improved CDVA and CS in keratoconus patients. Practitioners should be aware of this distinct feature of SLs and use it as needed to improve visual performance.

Assessment of genomic breeding values and their accuracies for carcass traits in Jeju Black cattle using whole-genome SNP chip panels.

The objective of the present study was to evaluate the breeding value and accuracy of genomic estimated breeding values (GEBVs) of carcass traits in Jeju Black cattle (JBC) using Hanwoo steers and JBC as a reference population using the single-trait animal model. Our research included genotype and phenotype information on 19,154 Hanwoo steers with 1097 JBC acting as the reference population. Likewise, the test population consisted of 418 genotyped JBC individuals with no phenotypic records for those carcass traits. For estimating the accuracy of GEBV, we divided the entire population into three groups. Hanwoo and JBC make up the first group; Hanwoo and JBC, who has both the genotype and phenotypic records, are referred to as the reference (training) population, and JBC, who lacks phenotypic information is referred to as the test (validation) population. The second group consists of the JBC (without phenotype) as the test population and Hanwoo as a reference population with phenotype and genotypic data. The only JBCs in the third group are those who have genotypic and phenotypic data on them as a reference population but no phenotypic data on them as a test population. The single-trait animal model was used in all three groups for statistical purposes. The reference populations estimated heritabilities for carcass weight (CWT), eye muscle area (EMA), backfat thickness (BF), and marbling score (MS) as 0.30, 0.26, 0.26, and 0.34 for the Hanwoo steer and 0.42, 0.27, 0.26, and 0.48 for JBC. The average accuracy for carcass traits in Group 1 was 0.80 for the Hanwoo and JBC reference population compared with 0.73 for the JBC test population. Although the average accuracy for carcass traits in Group 2 was 0.80, it was 0.80 for the Hanwoo reference population and only 0.56 for the JBC test population. The average accuracy for the JBC reference and test populations was 0.68 and 0.50, respectively, when they were included in the accuracy comparison without the Hanwoo reference population. Groups 1 and 2 used Hanwoo as reference population, which led to a better average accuracy; however, Group 3 only used the JBC reference and test population, which led to a lower average accuracy. This might be due to the fact that Group 3 used a smaller reference size than the group that came before it and that the genetic makeup of the Hanwoo and JBC breeds differed. The GEBV accuracy for MS was higher than that of other traits across all three analysis groups, followed by CWT, EMA, and BF, which may be partially explained by the MS traits' higher heritability. This study suggests that in order to achieve more accuracy, a large reference population particular to a breed should be established. Therefore, to increase the accuracy of GEBV prediction and the genetic benefit from genomic selection in JBC, individual reference breeds, and large populations are required.