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BackgroundMicrobial keratitis is one of the leading causes of blindness globally. An overactive immune response during an infection can exacerbate damage, causing corneal opacities and vision loss. This study aimed to identify the differentially expressed genes between corneal infection patients and healthy volunteers within the cornea and conjunctiva and elucidate the contributing pathways to these conditions’ pathogenesis. Moreover, it compared the corneal and conjunctival transcriptomes in corneal-infected patients to cytokine levels in tears.MethodsCorneal and conjunctival swabs were collected from seven corneal infection patients and three healthy controls under topical anesthesia. RNA from seven corneal infection patients and three healthy volunteers were analyzed by RNA sequencing (RNA-Seq). Tear proteins were extracted from Schirmer strips via acetone precipitation from 38 cases of corneal infection and 14 healthy controls. The cytokines and chemokines IL-1β, IL-6, CXCL8 (IL-8), CX3CL1, IL-10, IL-12 (p70), IL-17A, and IL-23 were measured using an antibody bead assay.ResultsA total of 512 genes were found to be differentially expressed in infected corneas compared to healthy corneas, with 508 being upregulated and four downregulated (fold-change (FC) 2 and adjusted p

Objective:. Intent-to-treat analysis follows patients from listing to death, regardless of their transplant status, and aims to provide a more holistic scope of the progress made in adult solid-organ transplantation. Background:. Many studies have shown progress in waitlist and post-transplant survival for adult kidney, liver, heart, and lung transplants, but there is a need to provide a more comprehensive perspective of transplant outcomes for patients and their families. Methods:. Univariable and multivariable Cox regression analyses were used to analyze factors contributing to intent-to-treat survival in 813,862 adults listed for kidney, liver, heart, and lung transplants. The Kaplan–Meier method was used to examine changes in waitlist, post-transplant, and intent-to-treat survival. Transplantation rates were compared using χ2 tests. Results:. Intent-to-treat survival has steadily increased for liver, heart, and lung transplants. The percentage of patients transplanted within 1 year significantly increased for heart (57.4% from 52.9%) and lung (73.5% from 33.2%). However, the percentage of patients transplanted within 1 year significantly decreased from 35.8% to 21.2% for kidney transplant. Notably, intent-to-treat survival has decreased for kidneys despite increases in waitlist and post-transplant survival, likely because of the decreased transplant rate. Conclusion:. Intent-to-treat survival steadily improved for liver, heart, and lung transplant over the 30-year study period. Continued advancements in allocation policy, immunosuppression, and improved care of patients on the waitlist may contribute to further progress in outcomes of all organs, but the increasing discrepancy in supply and demand of donor kidneys is alarming and has impeded the progress of kidney intent-to-treat survival.

Constraining uncertainty in the global carbon cycle requires valid assessment of both surface and stored carbon in marine and coastal ecosystems (Blue Carbon) as well as terrestrial carbon (forests, peatlands, and soils) [Pendleton et al., 2012]. Quantifying the global carbon stock of coastal salt marshes, potentially the most efficient carbon-burying ecosystems in the world per area, is a key area of further research in both of these fields Pendleton et al., 2012. One of the largest challenges is that despite the fact that salt marshes often sequester carbon several meters deep, nearly all estimates of salt marsh carbon stocks consider only the upper 1 m of sediment (Windham-Myers et al., 2015) [54]. This is particularly concerning because coastal wetlands are increasingly at risk due to climate change, sea level rise, and anthropogenic disturbance and destruction (Deegan et al., 2012) [15]. Using full-depth measurements from marsh cores, we estimate the carbon stock of five salt marshes in the highly urbanized estuary of Jamaica Bay, New York and argue that partial-depth measurements can underestimate carbon stocks. These estimates use calculated carbon content and probe depth data of these marshes collected between 2000 and 2019, applying this data across the full area of the marsh obtained from satellite imagery. Carbon density measurements are then multiplied by the full-depth volume of the marshes to create an estimate of total carbon stock. In addition to calculating present-day estimates, we compare our carbon stock estimates to historical Jamaica Bay imagery to calculate historical carbon stocks and carbon loss. The carbon stock estimates presented here show a 95% carbon stock loss between 1885 and 2019 in Jamaica Bay and highlight the severe underestimation of carbon stocks without full-depth calculations. These findings have important implications for disappearing salt marshes with regard to the global carbon cycle and the incorporation of belowground carbon into global climate models. The findings are increasingly relevant for advocacy efforts aiming to conserve these marshes with sea level rise.

To prevent the global average temperature from increasing more than 1.5°C and lower the concentration of greenhouse gases (GHGs) in the atmosphere, most emissions trajectories necessitate the implementation of strategies that include both GHG mitigation and negative emissions technologies (NETs). For NETs, there are unique research challenges faced by both CO2 capture and utilization to scale in an economically feasible manner. Starting with incumbent methods, wherein CO2 is recovered from a high concentration source, and moving toward CO2 capture from more widely available dilute sources, we outline how CO2 capture systems interface with downstream utilization in flow reactors. To provide a real-world point of comparison, we analyze CO2 sourcing for Air Company's CO2-to-alcohols pilot and demonstration scale deployments in Brooklyn, New York, USA and Calgary, Alberta, Canada as case studies. The degree of reduction in atmospheric CO2 depends on product alcohol usage; for example, use as a fixed chemical feedstock provides longer term emissions reduction than as a fuel, which is eventually oxidized. Lastly, we discuss the barriers that are present for economic scale-up of CO2 capture and utilization technologies broadly.

Leimyosarcomas arising from the stroma of the prostate are very rare, accounting for 0.1% of malignancies. We describe a case that closely mimicked benign prostatic hypertrophy on magnetic resonance imaging. Due to the low incidence of disease there is no high level evidence for management. We advocate neoadjuvant radiotherapy followed by radical prostatectomy with pelvic lymph node dissection. Diagnosis and expedient management is critical.

Axolotls and other salamanders can regenerate entire limbs after amputation as adults, and much recent effort has sought to identify the molecular programs controlling this process. While targeted mutagenesis approaches like CRISPR/Cas9 now permit gene-level investigation of these mechanisms, genetic screening in the axolotl requires an extensive commitment of time and space. Previously, we quantified CRISPR/Cas9-generated mutations in the limbs of mosaic mutant axolotls before and after regeneration and found that the regenerated limb is a highfidelity replicate of the original limb (Flowers et al. 2017). Here, we circumvent aforementioned genetic screening limitations and present methods for a multiplex CRISPR/Cas9 haploid screen in chimeric axolotls (MuCHaChA), which is a novel platform for haploid genetic screening in animals to identify genes essential for limb regeneration.

Background: The population of many countries is aging and a significant number of elderly patients with soft-tissue sarcoma are being seen at cancer centers. The unique therapeutic and prognostic implications of treating soft-tissue sarcoma in geriatric patients warrant further consideration in order to optimize outcomes.Patients and Methods: This is a single-institution retrospective study of consecutive non-metastatic primary extremity and trunk high-grade sarcomas surgically treated between 1996 and 2012, with at least 2 years of follow-up for survivors. Patient characteristics and oncological outcomes were compared between age groups (≥80 vs.

Across many southern regions of Australia, native grasslands have become seriously threatened by human activity, with only a fraction of the original areas remaining undisturbed. In particular, the introduction and establishment of exotic invasive weeds has caused significant degradation to the ecosystems in these areas by contributing to a decrease in native plant density and diversity, and this has ultimately led to major changes to the ecosystem structure and function. One such example is Galenia pubescens. Our objective of this study was to assess the effectiveness of four different attempts to control G. pubescens: herbicide control with glyphosate; organic herbicide control with pine oil; the application of mulch; and the addition of seeds of native species to the seedbank. Results shows that any one single control strategy is insufficient to control G. pubescens, and, in addition, it has shown that regeneration of native vegetation is limited unless direct seeding is applied. There was a strong indication that a combined strategy employing more than two of the aforementioned techniques is likely to be the most effective approach, at least in the short term. Underscoring the complexity of this task, our analysis on foliage cover of G. pubescens shows that the interaction of pine oil and glyphosate treatments appeared to be very effective after six months, but were not so effective after 18 months. By contrast, seeding with native seeds was not particularly effective at six months, but its longer-term contribution appears to be effective at 18 months. Further, our results obtained from the seedbank abundance study indicate that time alone was not a significant factor in restoration of the grasslands (p = 0.165); however there were interactions with time, shown by time*glyphosate (p = 0.008) and time*seeding (p = 0.016). Both interactions indicated that the applications of glyphosate and seeding were more beneficial after 18 months compared to six months. However, full regeneration of invaded native grasslands may not be possible unless further restoration programs are re-implemented after the first cycle of G. pubescens' treatments have been completed.

Salamanders are unparalleled among tetrapods in their ability to regenerate many structures, including entire limbs, and the study of this ability may provide insights into human regenerative therapies. The complex structure of the limb poses challenges to the investigation of the cellular and molecular basis of its regeneration. Using CRISPR/Cas, we genetically labelled unique cell lineages within the developing axolotl embryo and tracked the frequency of each lineage within amputated and fully regenerated limbs. This allowed us, for the first time, to assess the contributions of multiple low frequency cell lineages to the regenerating limb at once. Our comparisons reveal that regenerated limbs are high fidelity replicas of the originals even after repeated amputations.

We report the early results of nine patients with periacetabular malignancies treated with Enneking and Dunham type 2 resection and reconstruction using extracorporeally irradiated (ECI) tumour bone combined with total hip arthroplasty (THA). Diagnosis was chondrosarcoma in six patients, osteosarcoma in two patients, and metastatic renal cell carcinoma in one patient. All patients underwent surgical resection and the resected specimen was irradiated with 50 Gy in a single fraction before being prepared for reimplantation as a composite autograft. The mean follow-up was 21 months (range, 3–59). All patients were alive at latest follow-up. No local recurrence was observed. One patient serially developed three pulmonary metastases, all of which were resected. One experienced hip dislocation due to incorrect seating of an acetabular liner. This was successfully treated with revision of the liner with no further episodes of instability. There were no cases of deep infection or loss of graft. The average Musculoskeletal Tumor Society (MSTS) score was 75% (range, 57–87%). Type 2 pelvic reconstruction with ECI and THA has shown excellent early oncological and functional results in our series. Preservation of the gluteus maximus and hip abductors is important for joint stability and prevention of infection.

Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS). We investigated the cell specific gene and protein expression variation controlled by the CD40 genetic variant(s) associated with MS, i.e. the T-allele at rs1883832. Previously we had shown that the risk allele is expressed at a lower level in whole blood, especially in people with MS. Here, we have defined the immune cell subsets responsible for genotype and disease effects on CD40 expression at the mRNA and protein level. In cell subsets in which CD40 is most highly expressed, B lymphocytes and dendritic cells, the MS-associated risk variant is associated with reduced CD40 cell-surface protein expression. In monocytes and dendritic cells, the risk allele additionally reduces the ratio of expression of full-length versus truncated CD40 mRNA, the latter encoding secreted CD40. We additionally show that MS patients, regardless of genotype, express significantly lower levels of CD40 cell-surface protein compared to unaffected controls in B lymphocytes. Thus, both genotype-dependent and independent down-regulation of cell-surface CD40 is a feature of MS. Lower expression of a co-stimulator of T cell activation, CD40, is therefore associated with increased MS risk despite the same CD40 variant being associated with reduced risk of other inflammatory autoimmune diseases. Our results highlight the complexity and likely individuality of autoimmune pathogenesis, and could be consistent with antiviral and/or immunoregulatory functions of CD40 playing an important role in protection from MS.

The IL7Rα gene is unequivocally associated with susceptibility to multiple sclerosis (MS). Haplotype 2 (Hap 2) confers protection from MS, and T cells and dendritic cells (DCs) of Hap 2 exhibit reduced splicing of exon 6, resulting in production of relatively less soluble receptor, and potentially more response to ligand. We have previously shown in CD4 T cells that IL7Rα haplotypes 1 and 2, but not 4, respond to interferon beta (IFNβ), the most commonly used immunomodulatory drug in MS, and that haplotype 4 (Hap 4) homozygotes have the highest risk of developing MS. We now show that IL7R expression increases in myeloid cells in response to IFNβ, but that the response is haplotype-dependent, with cells from homozygotes for Hap 4 again showing no response. This was shown using freshly derived monocytes, in vitro cultured immature and mature monocyte-derived dendritic cells, and by comparing homozygotes for the common haplotypes, and relative expression of alleles in heterozygotes (Hap 4 vs not Hap 4). As for T cells, in all myeloid cell subsets examined, Hap 2 homozygotes showed a trend for reduced splicing of exon 6 compared to the other haplotypes, significantly so in most conditions. These data are consistent with increased signaling being protective from MS, constitutively and in response to IFNβ. We also demonstrate significant regulation of immune response, chemokine activity and cytokine biosynthesis pathways by IL7Rα signaling in IFNβ -treated myeloid subsets. IFNβ-responsive genes are over-represented amongst genes associated with MS susceptibility. IL7Rα haplotype may contribute to MS susceptibility through reduced capacity for IL7Rα signalling in myeloid cells, especially in the presence of IFNβ, and is currently under investigation as a predictor of therapeutic response.

Orientalism, as a paradigm expounded by Edward W. Said, has been influential in literary studies. Here it is critically evaluated with reference to Augustan poetry, in relation to three different ethnic groups : Indians, Egyptians and Parthians. The shield of Aeneas is the point of departure. Some of the shortcomings of Saidian Orientalism can be circumvented by the adoption of concepts from human geography.

Influenza A infection is a global disease that has been responsible for four pandemics over the last one hundred years. However, it remains poorly understood as to why some infected individuals succumb to life threatening complications whilst others recover and are relatively unaffected. Using gene-expression analysis of circulating leukocytes, here we show that the progression towards severe influenza A infection is characterised by an abnormal transcriptional reprogramming of cell cycle and apoptosis pathways. In severely infected humans, leukocyte gene-expression profiles display opposing cell cycle activities; an increased aberrant DNA replication in the G(1)/S phase yet delayed progression in the G(2)/M phase. In mild infection, cell cycle perturbations are fewer and are integrated with an efficient apoptotic program. Importantly, the loss of integration between cell cycle perturbations and apoptosis marks the transition from a mild viral illness to a severe, life threatening infection. Our findings suggest that circulating immune cells may play a significant role in the evolution of the host response. Further study may reveal alternative host response factors previously unrecognized in the current disease model of influenza.

Abstract Background The facial branchiomotor neurons of cranial nerve VII undergo a stereotyped tangential migration in the zebrafish hindbrain that provides an ideal system for examining the complex interactions between neurons and their environment that result in directed migration. Several studies have shown the importance of the planar cell polarity pathway in facial branchiomotor neuron migration but the role of apical-basal polarity has not been determined. Here we examine the role of the PAR-aPKC complex in forming the basal structures that guide facial branchiomotor neurons on an appropriate migratory path. Results High resolution timelapse imaging reveals that facial branchiomotor neurons begin their migration by moving slowly ventrally and posteriorly with their centrosomes oriented medially and then, upon contact with the Laminin-containing basement membrane at the rhombomere 4-rhombomere 5 boundary, speed up and reorient their centrosomes on the anterior-posterior axis. Disruption of the PAR-aPKC complex members aPKCλ, aPKCζ, and Pard6gb results in an ectopic ventral migration in which facial branchiomotor neurons escape from the hindbrain through holes in the Laminin-containing basement membrane. Mosaic analysis reveals that the requirement for aPKC is cell-nonautonomous, indicating that it is likely required in the surrounding polarized neuroepithelium rather than in facial motor neurons themselves. Ventral facial motor neuron ectopia can be phenocopied by mutation of lamininα1, suggesting that it is defects in maintenance of the laminin-containing basement membrane that are the likely cause of ventral mismigration in aPKCλ+ζ double morphants. Conclusions Our results suggest that the laminin-containing ventral basement membrane, dependent on the activity of the PAR-aPKC complex in the hindbrain neuroepithelium, is both a substrate for migration and a boundary that constrains facial branchiomotor neurons to the appropriate migratory path.

Abstract Background Syndromic surveillance is increasingly being evaluated for its potential for early warning of increased disease activity in the population. However, interpretation is hampered by the difficulty of attributing a causative pathogen. We described the temporal relationship between laboratory counts of influenza and respiratory syncytial virus (RSV) detection and alternative groupings of Emergency Department (ED) respiratory diagnoses. Methods ED and laboratory data were obtained for the south-eastern area of Sydney, NSW for the period 1 June 2001 - 1 December 2006. Counts of ED visits and laboratory confirmed positive RSV and influenza cases were aggregated by week. Semi-parametric generalized additive models (GAM) were used to determine the association between the incidence of RSV and influenza and the incidence of respiratory syndrome ED presentations while controlling for temporal confounders. Results For every additional RSV laboratory count, ED diagnoses of bronchiolitis increased by 3.1% (95%CI: 2.7%-3.5%) in the same week. For every additional influenza laboratory count, ED diagnoses of influenza-like illness increased by 4.7% (95%CI: 4.2%-5.2%) one week earlier. Conclusion In this study, large increases in ED diagnoses of bronchiolitis and influenza-like illness were independent and proxy indicators for RSV and influenza activity, respectively.