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Background: There is a paucity of recent literature investigating the sole effect of income level on the treatment and survival of patients with rectal cancer., Methods: We analyzed all cases of rectal cancer in the Rectal Cancer PUF of the NCDB from 2010 to 2020. We utilized the Median Income Quartiles 2016-2020 to define our income levels. The two lower quartiles were combined to create a lower income group, with the upper two quartiles creating the higher income group. The total cohort included 201,329 patients, with 116,843 and 84,486 in the higher and lower income groups, respectively., Results: Lower income patients were more often black (17 % vs 6 %), lived farther from the nearest hospital (33.5 miles vs 25.7 miles) despite being more likely to live in urban areas (25 % vs 7 %), and had lower levels of private insurance (36 % vs 49 %). They underwent more APRs (17 % vs 14 %) and had a 13 % higher chance of undergoing an open operation (OR 1.13, CI 1.09-1.17). Higher income patients had a 12 % reduction in 90-day (OR 0.88, 95 % CI 0.82-0.96) and overall mortality (OR 0.88, 95 % CI 0.86-0.89)., Conclusions: Clinicians should be aware that lower income patients are often faced with unique challenges that may impact care delivery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (© 2024 The Authors. Published by Elsevier Ltd.)

Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GECs), podocytes, and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis. GECs form a lumenized vascular network, which regresses in response to TGFβ. MCs respond to TGFβ by forming glomerulosclerotic-like nodules with matrix deposition. TGFβ treatment of podocytes does not alter cell morphology but increases connective tissue growth factor (CTGF) expression. BMP7 prevents TGFβ-induced GEC network regression, whereas TGFβ-induced MC nodule formation is prevented by SMAD3 siRNA knockdown or ALK5 inhibitors but not BMP7, and increased phospho-SMAD3 was observed in human glomerulosclerosis. In 3D tri-culture, GECs, podocytes, and MCs form a vascular network in which GECs and podocytes interact intimately within a matrix containing MCs. TGFβ treatment induces formation of nodules, but combined inhibition of ALK5 and CTGF is required to prevent TGFβ-induced nodule formation in tri-cellular cultures. Identification of therapeutic targets for glomerulosclerosis depends on the 3D culture of all three glomerular cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: This study aims to use 30-day readmission rates to investigate the presumption that men and women with learning disabilities (LDs, known internationally as intellectual disabilities) receive poorer quality hospital care than their non-disabled peers., Method: A 12-month retrospective audit was conducted using Hospital Episode Statistics (HES) at a single acute hospital in the East of England. This identified all in-patient admissions; admissions where the person concerned was recognised as having a LD; and all emergency readmissions within 30 days of discharge. Additionally, the healthcare records of all patients identified as having a LD and readmitted within 30 days as a medical emergency were examined in order to determine whether or not these readmissions were potentially preventable., Results: Over the study period, a total of 66 870 adults were admitted as in-patients, among whom 7408 were readmitted as medical emergencies within 30 days of discharge: a readmission rate of 11%. Of these 66 870 patients, 256 were identified as having a LD, with 32 of them experiencing at least one emergency readmission within 30 days: a readmission rate of 13%. When examined, the healthcare records pertaining to these 32 patients who had a total of 39 unique 30-day readmissions revealed that 69% (n = 26) of these readmissions were potentially preventable., Conclusion: Although overall readmission rates were similar for patients with LDs and those from the general population, patients with LDs had a much higher rate of potentially preventable readmissions when compared to a general population estimate from van Walraven et al. This suggests that there is still work to be done to ensure that this patient population receives hospital care that is both safe and of high quality., (© 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Objectives: Inflammatory bowel disease (IBD) is heritable, but a total of 163 variants commonly implicated in IBD pathogenesis account for only 25% of the heritability. Rare, highly penetrant genetic variants may also explain mendelian forms of IBD and some of the missing heritability. To test the hypothesis that rare loss-of-function mutations can be causative, we performed whole exome sequencing (WES) on 5 members of a 2-generation family of European ancestry presenting with an early-onset and atypical form of IBD., Methods: WES was performed for all of the 5 family members; the mother and 3 male offspring were affected, whereas the father was unaffected. Mapping, annotation, and filtering criteria were used to reduce candidate variants. For functional testing we performed forkhead box P3 (FOXP3) staining and a T-cell suppression assay., Results: We identified a novel missense variant in exon 6 of the X-linked FOXP3 gene. The c.694A>C substitution in FOXP3 results in a cysteine-to-glycine change at the protein position 232 that is completely conserved among all vertebrates. This variant (heterozygous in the mother and hemizygous in all 3 affected sons) did not impair FOXP3 protein expression, but significantly reduced the ability of the host's T regulatory cells to suppress an inappropriate autoimmune response. The variant results in a milder immune dysregulation, polyendocrinopathy, enteropathy, and X-linked phenotype with early-onset IBD., Conclusions: Our study illustrates the successful application of WES for making a definitive molecular diagnosis in a case of multiply affected families, with atypical IBD-like phenotype. Our results also have important implications for disease biology and disease-directed therapeutic development.

The endothelial cell has a remarkable ability for sub-specialisation, adapted to the needs of a variety of vascular beds. The role of developmental programming versus the tissue contextual environment for this specialization is not well understood. Here we describe a hierarchy of expression of HOX genes associated with endothelial cell origin and location. In initial microarray studies, differential gene expression was examined in two endothelial cell lines: blood derived outgrowth endothelial cells (BOECs) and pulmonary artery endothelial cells. This suggested shared and differential patterns of HOX gene expression between the two endothelial lines. For example, this included a cluster on chromosome 2 of HOXD1, HOXD3, HOXD4, HOXD8 and HOXD9 that was expressed at a higher level in BOECs. Quantative PCR confirmed the higher expression of these HOXs in BOECs, a pattern that was shared by a variety of microvascular endothelial cell lines. Subsequently, we analysed publically available microarrays from a variety of adult cell and tissue types using the whole "HOX transcriptome" of all 39 HOX genes. Using hierarchical clustering analysis the HOX transcriptome was able to discriminate endothelial cells from 61 diverse human cell lines of various origins. In a separate publically available microarray dataset of 53 human endothelial cell lines, the HOX transcriptome additionally organized endothelial cells related to their organ or tissue of origin. Human tissue staining for HOXD8 and HOXD9 confirmed endothelial expression and also supported increased microvascular expression of these HOXs. Together these observations suggest a significant involvement of HOX genes in endothelial cell positional identity.

Tumour necrosis factor (TNF) was originally described as a circulating factor that can induce haemorrhagic necrosis of tumours. It is now clear that TNF has many different functions in cancer biology. In addition to causing the death of cancer cells, TNF can activate cancer cell survival and proliferation pathways, trigger inflammatory cell infiltration of tumours and promote angiogenesis and tumour cell migration and invasion. These effects can be explained by the diverse cellular responses TNF can initiate through distinct signal transduction pathways, opening the way for more selective targeting of TNF signalling in cancer therapy., (Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

TNF signals through two distinct receptors, designated TNFR1 and TNFR2, which initiate diverse cellular effects that include cell survival, activation, differentiation, and proliferation and cell death. These cellular responses can promote immunological and inflammatory responses that eradicate infectious agents, but can also lead to local tissue injury at sites of infection and harmful systemic effects. Defining the molecular mechanisms involved in TNF responses, the effects of natural and experimental genetic diversity in TNF signalling and the effects of therapeutic blockade of TNF has increased our understanding of the key role that TNF plays in infectious disease., (Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

We describe a method for coculture of macro- or microvascular human endothelial cells (ECs) and pericytes (PCs) within a 3-dimensional (3-D) protein matrix resulting in lumenized EC cords invested by PCs. To prevent apoptotic cell death of ECs in 3-D culture, human umbilical vein or dermal microvascular ECs were transduced to express the antiapoptotic protein Bcl-2. To prevent PC-mediated gel contraction, the collagen-fibronectin gel was polymerized within a polyglycolic acid nonwoven matrix. Over the first 24-48 h, EC-only gels spontaneously formed cords that developed lumens via vacuolization; such vascular networks were maintained for up to 7 days. In EC-PC cocultures, PCs were recruited to the EC networks. PC investment of EC cords both limited the lumen diameter and increased the degree of vascular network arborization. Peg and socket junctions formed between ECs and PCs in this system, but dye transfer, indicative of gap junction formation, was not observed. This simple system can be used to analyze bidirectional signals between ECs and PCs in a 3-D geometry.

Performance data characterizing a direct optical activation device that operates either pneumatically or hydraulically are presented. This direct conversion device for optical signals offers immunity to electromagnetic interference and provides an alternative to electrooptic and electromechanical valves for actuation. The device uses a modified fluidic laminar proportional amplifier, employing laser induced deflection of the fluidic supply jet to perform the signal conversion. The pneumatic version operates at a supply pressure of 20.7 kPa having a gain of 15.5 kPa/W of optical power and a bandwidth of 140 Hz. The hydraulic version of the device operates with MIL-5606 hydraulic oil pressurized to a supply pressure of 1300 kPa. The hydraulic version has a gain of 170 kPa/W of input optical power and a bandwidth of 170 Hz. Experiments have determined that the laser induced deflection of the supply jet is a result of optical modulation of the fluid viscosity which creates an asymmetric jet flow.

A method is described for lessening the stringent vibration isolation requirements associated with conventional cw holography. This is accomplished by focusing a portion of the laser illuminating beam to a spot on the object, which then serves as a speckle reference beam for recording the object. In addition to the reduction of vibration isolation requirements, other features of the technique are as follows: Several holograms of the same scene, with different viewing directions, can be recorded simultaneously without additional reference beams, and vibration isolation requirements on the holographic plate are no greater than those associated with conventional photography. The method can also be used to determine relative phase between two points on a vibrating surface. In pulsed holography, the method can be used to eliminate residual fringes between recordings of pulsed holographic interferograms.