Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

Name-calling by a child diagnosed with asperger’s syndrome

Rendle-Short, Wilkinson, and Danby show how social interaction is directly relevant to maintaining friendships, mental health and well-being, and supportive peer relations. Using conversation analysis, the chapter focuses on conversational participants’ pursuit of affiliation and intimacy from a language as action perspective. It focuses on the use of derogatory naming practices by a 10-year-old girl diagnosed with Asperger’s Syndrome. The analysis shows how derogatory address terms, part of a wider pattern of behaviour evident in this child’s interaction, result in behaviour that might be thought of as impolite or lacking in restraint. It also illustrates how a single case study can draw attention to the context-specific nature of interaction when working with children with Asperger’s Syndrome. The chapter contributes to our understanding of the difficulty in pinpointing, with precision and with clear evidence, what counts as a ‘social interaction difficulty’ due to the context specific nature of interaction.

IMU aided 3D visual odometry for car-like vehicles

We present a method for calculating odome- try in three-dimensions for car-like ground ve- hicles with an Ackerman-like steering model. In our approach we use the information from a single camera to derive the odometry in the plane and fuse it with roll and pitch informa- tion derived from an on-board IMU to extend to three-dimensions, thus providing odometric altitude as well as traditional x and y transla- tion. We have mounted the odometry module on a standard Toyota Prado SUV and present results from a car-park environment as well as from an off-road track.

Coverage algorithms for an under-actuated car-like vehicle in an uncertain environment

A coverage algorithm is an algorithm that deploys a strategy as to how to cover all points in terms of a given area using some set of sensors. In the past decades a lot of research has gone into development of coverage algorithms. Initially, the focus was coverage of structured and semi-structured indoor areas, but with time and development of better sensors and introduction of GPS, the focus has turned to outdoor coverage. Due to the unstructured nature of an outdoor environment, covering an outdoor area with all its obstacles and simultaneously performing reliable localization is a difficult task. In this paper, two path planning algorithms suitable for solving outdoor coverage tasks are introduced. The algorithms take into account the kinematic constraints of an under-actuated car-like vehicle, minimize trajectory curvatures, and dynamically avoid detected obstacles in the vicinity, all in real-time. We demonstrate the performance of the coverage algorithm in the field by achieving 95% coverage using an autonomous tractor mower without the aid of any absolute localization system or constraints on the physical boundaries of the area.

Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Background Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure. Results Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope. Conclusions Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.

If you're going to be a leader, at least act like it! Prejudice towards women who are tentative in leader roles

Role congruity theory predicts prejudice towards women who meet the agentic requirements of the leader role. In line with recent findings indicating greater acceptance of agentic behaviour from women, we find evidence for a more subtle form of prejudice towards women who fail to display agency in leader roles. Using a classic methodology, the agency of male and female leaders was manipulated using assertive or tentative speech, presented through written (Study 1, N = 167) or verbal (Study 2, N = 66) communications. Consistent with predictions, assertive women were as likeable and influential as assertive men, while being tentative in leadership reduced the likeability and influence of women, but not of men. Although approval of agentic behaviour from women in leadership reflects progress, evidence that women are quickly singled out for disapproval if they fail to show agency is important for understanding how they continue to be at a distinct disadvantage to men in leader roles.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

BACKGROUND Tilted disc syndrome (TDS) is associated with characteristic ocular findings. The purpose of this study was to evaluate the ocular, refractive, and biometric characteristics in patients with TDS. METHODS This case-control study included 41 eyes of 25 patients who had established TDS and 40 eyes of 20 healthy control subjects. All participants underwent a complete ocular examination, including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry, keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. RESULTS There were no significant differences in spherical equivalent (P = 0.13) and total astigmatism (P = 0.37) between groups. However, mean best spectacle-corrected visual acuity (Log Mar) was significantly worse in TDS patients (P = 0.003). The lenticular astigmatism was greater in the syndrome group, whereas the corneal component was greater in controls (P = 0.059 and P = 0.028, respectively). The measured biometric features were the same in both groups, except for the lens thickness and lens-axial length factor, which were greater in the TDS group (P = 0.007 and P = 0.055, respectively). CONCLUSIONS Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lenses were characteristic findings in patients with TDS.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

Purpose: To evaluate the ocular refractive and biometric characteristics in patients with tilted disc syndrome (TDS). Methods: This case-control study comprised 41 eyes of 25 patients with established TDS and forty eyes of 20 age- and sex-matched healthy control subjects. All had a complete ocular examination including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. Results: There were no significant differences in spherical equivalent (p = 0.334) and total astigmatism (p= 0.246) between groups. However, mean best spectacular corrected visual acuity was significantly worse in TDS patients (P < 0.001). The lenticular astigmatism was significantly greater in the syndrome group, while the corneal component was greater in the controls (p = 0.004 and p = 0.002, respectively). The measured biometric features were the same in both groups, except for the lens thickness, relative lens position, and lens-axial length factor which were greater in the TDS group (p = 0.002, p = 0.015, and p = 0.025, respectively). Conclusions: Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lens were characteristic findings in patients with TDS.

“They are like family”: The emotional cost experienced by nurses when caring for haemodialysis patients

Background Haemodialysis (HD) nursing is characterised by frequent, intense interactions with patients over long periods of time resulting in a unique nurse-patient relationship. Due to the life-limiting nature of end-stage renal failure, nurses are likely to have repeated exposures to the death of patients with whom they have formed relationships. Repeated exposure to patient death translates into frequent grief experiences. There is scant literature on the psychological impact of patient death for nurses working in the HD setting. Aims To explore HD nurses experiences of patient death and coping mechanisms used. Methods A sequential mixed method study investigating job satisfaction, stress and burnout found that HD nurses had high levels of stress and burnout. These results were explored in more detail during 8 semi-structured interviews with HD nurses. Interviews were audio-recorded, transcribed verbatim and subjected to thematic analysis. Results Three themes were identified that highlight the stress experienced by nurses when a haemodialysis patient dies. The first theme, “quazi-family” describes the close relationship which forms between nurses and patients. The “complicated grief” theme outlines the impact of death on HD nurses, and the final theme, “remembrance” explains some of the coping mechanisms used in the grieving process. Conclusion Nurses develop individual coping mechanisms to accommodate the grief and loss experienced when a “close” patient dies. The grieving process caused by the death of patient’s needs to be recognised by nurses and nurse managers as causing psychological stress and strain.

Superior perilimbal epitheliopathy in recurrent corneal erosion syndrome

Purpose To highlight the finding of occult areas of poor epithelial adhesion in the superior perilimbal cornea in a minority of patients with recalcitrant recurrent corneal erosion syndrome presenting with corneal erosion elsewhere on the corneal surface. Patient population 31 eyes of 31 consecutive patients with corneal erosion undergoing mechanical debridement of the epithelium prior to diamond burr keratectomy for recurrent corneal erosion. Methods Determine the location and incidence of poor epithelial adhesion distant from the initial erosion by use of mechanical debridement with a dry microsponge. Results During debridement, 8 of 31 eyes (25.8%) displayed a large arcuate area of occult dysfunction of adhesion in the superior perilimbal area. None of these patients showed recurrence over a mean of 18 month after diamond burr keratectomy (95% confidence interval 0-36.9%). Conclusion Mechanical debridement with a microsponge identified a significant minority of patients with poor adhesion in the superior perilimbal cornea away from the area of obvious erosion and increased the target area for diamond burr keratectomy. This two pronged approach allowed successful management of this group.

Measuring, understanding and reducing psychotic-like experiences (PLEs) in young people

Using large community samples, an existing screening instrument for unusual beliefs and perceptual experiences was refined, and a current version of the lifetime measure was developed and tested. Importantly, high scores on the instruments were associated with psychological distress and suicide risk. Acceptability testing of a web treatment was also undertaken. Routine use of the screening instrument and web program in health services may improve identification and support of young people at risk of distress and serious psychological disorder.

Surgical fusion of early onset severe scoliosis increases survival in the child with rett syndrome: A population based study

Introduction. Rett Syndrome is a rare genetic neurodevelopmental disorder usually affecting females. Scoliosis is a common comorbidity and spinal fusion may be recommended if severe. Little is known about long term outcomes. We examined the impact of spinal fusion on survival and risk of severe lower respiratory tract infection (LRTI) in Rett Syndrome. Methods Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry of Rett Syndrome cases established in 1993, and the Australian Institute of Health and Welfare National Death Index database. An extended Cox regression model was used to estimate the effect of spinal surgery on survival in females who developed severe scoliosis (Cobb angle > 45 degrees). Generalized estimating equation modelling was used to estimate the effect of spinal surgery on the odds of developing severe LRTI. Results Severe scoliosis was identified in 140 cases (60.3%) of whom slightly fewer than half (48.6%) developed scoliosis prior to eight years of age. Scoliosis surgery was performed in 98 (69.0%) of those at a median age of 13 years 3 months (IQR 11 years 5 months – 14 years 10 months). After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (HR 0.30, 95% CI 0.12, 0.74, P = 0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06, 0.52, P = 0.002). Spinal fusion was not associated with reduction in the occurrence of a severe LRTI overall (OR 0.60, 95%CI 0.27, 1.33, P=0.206) but was associated with a large reduction in odds of severe LRTI among those with early onset scoliosis (OR 0.32, 95%CI 0.11, 0.93, P=0.036). Conclusion With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome.

Analysis of killer immunoglobulin-like receptor genes in ankylosing spondylitis

Objectives: To assess the possible association of killer immunoglobulin-like receptor (KIR) genes, specifically KIR3DL1, KIR3DS1 and KIR3DL2, with ankylosing spondylitis (AS). Methods: 14 KIR genes were genotyped in 200 UK patients with AS and 405 healthy controls using multiplex polymerase chain reaction. Sequence-specific oligonucleotide probes were used to subtype 368 cases with AS and 366 controls for 12 KIR3DL2 alleles. Differences in KIR genotypes and KIR3DL2 allele frequencies were assessed using the χp2p test. Results: KIR3DL1 and KIR3DS1 gene frequencies were very similar in cases with AS and controls (odds ratio = 1.5, 95% confidence interval 0.8 to 3.0, and odds ratio = 1.02, 95% confidence interval 0.2 to 5.3, respectively). KIR3DL2 allele frequencies were not significantly different between cases with AS and controls. Conclusions: Neither the KIR gene content of particular KIR haplotypes nor KIR3DL2 polymorphisms contribute to AS.

Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice

Objective Spondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However, in genetically prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP-70W163C-mutant (SKG) mice injected intraperitoneally with β-1,3-glucan (curdlan). Methods Eight weeks after curdlan injection in wild-type or IL-17A-/- SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti-IL-23 or anti-IL-22. Cytokine production and endoplasmic reticulum (ER) stress were determined in affected organs. Results In curdlan-treated SKG mice, arthritis, enthesitis, and ileitis were IL-23 dependent. Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in the ileum, where it amplified ER stress, goblet cell dysfunction, and proinflammatory cytokine production. IL-17A was pathogenic, while IL-22 was protective against ileitis. IL-22+CD3- innate-like cells were increased in lamina propria mononuclear cells of ileitis-resistant BALB/c mice, which developed ileitis after curdlan injection and anti-IL-22. Conclusion In response to systemic β-1,3-glucan, intestinal IL-23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL-17/IL-22-dependent enthesitis. Innate IL-22 production promotes ileal tolerance.

A systematic review of axillary web syndrome (AWS)

Introduction Axillary web syndrome (AWS) can result in early post-operative and long-term difficulties following lymphadenectomy for cancer and should be recognised by clinicians. This systematic review was conducted to synthesise information on AWS clinical presentation and diagnosis, frequency, natural progression, grading, pathoaetiology, risk factors, symptoms, interventions and outcomes. Methods Electronic searches were conducted using Cochrane, Pubmed, MEDLINE, CINAHL, EMBASE, AMED, PEDro and Google Scholar until June 2013. The methodological quality of included studies was determined using the Downs and Black checklist. Narrative synthesis of results was undertaken. Results Thirty-seven studies with methodological quality scores ranging from 11 to 26 on a 28-point scale were included. AWS diagnosis relies on inspection and palpation; grading has not been validated. AWS frequency was reported in up to 85.4 % of patients. Biopsies identified venous and lymphatic pathoaetiology with five studies suggesting lymphatic involvement. Twenty-one studies reported AWS occurrence within eight post-operative weeks, but late occurrence of greater than 3 months is possible. Pain was commonly reported with shoulder abduction more restricted than flexion. AWS symptoms usually resolve within 3 months but may persist. Risk factors may include extensiveness of surgery, younger age, lower body mass index, ethnicity and healing complications. Low-quality studies suggest that conservative approaches including analgesics, non-steroidal anti-inflammatory drugs and/or physiotherapy may be safe and effective for early symptom reduction. Conclusions AWS appears common. Current evidence for the treatment of AWS is insufficient to provide clear guidance for clinical practice. Implications for Cancer Survivors Cancer survivors should be informed about AWS. Further investigation is needed into pathoaetiology, long-term outcomes and to determine effective treatment using standardised outcomes.