Mesenchymal stem cells for kidney transplantation

Published online: July 24, 2014The long term consequence of immunosuppressive therapy in kidney transplantation has prompted investigation of alternative means to modify the immune response to the allograft. Cell based therapies are potentially attractive as they may provide a long lasting immunomodulatory effect, may repair tissues and reduce the necessity to take immunosuppressive drug therapy. Of the current cell therapies, mesenchymal stem cells have now been trialled in small numbers of human kidney transplantation with apparent safety and potential efficacy. Many issues however need to be resolved before these cells will become mainstays of transplant immunosuppression including ex vivo modification to enhance immunomodulatory properties, cell number, route and frequency of administration as well as cellular source of origin.Bron Lett, Kisha N Sivanathan, P Toby Coate

COVID and the Kidney:An Update

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has led to a global pandemic that continues to be responsible for ongoing health issues for people worldwide. Immunocompromised individuals such as kidney transplant recipients and dialysis patients have been and continue to be among the most affected, with poorer outcomes after infection, impaired response to COVID-19 vaccines, and protracted infection. The pandemic also has had a significant impact on patients with underlying chronic kidney disease (CKD), with CKD increasing susceptibility to COVID-19, risk of hospital admission, and mortality. COVID-19 also has been shown to lead to acute kidney injury (AKI) through both direct and indirect mechanisms. The incidence of COVID-19 AKI has been decreasing as the pandemic has evolved, but continues to be associated with adverse patient outcomes correlating with the severity of AKI. There is also increasing evidence examining the longer-term effect of COVID-19 on the kidney demonstrating continued decline in kidney function several months after infection. This review summarizes the current evidence examining the impact of COVID-19 on the kidney, covering both the impact on patients with CKD, including patients receiving kidney replacement therapy, in addition to discussing COVID-19 AKI.<br/

COVID and the Kidney:An Update

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has led to a global pandemic that continues to be responsible for ongoing health issues for people worldwide. Immunocompromised individuals such as kidney transplant recipients and dialysis patients have been and continue to be among the most affected, with poorer outcomes after infection, impaired response to COVID-19 vaccines, and protracted infection. The pandemic also has had a significant impact on patients with underlying chronic kidney disease (CKD), with CKD increasing susceptibility to COVID-19, risk of hospital admission, and mortality. COVID-19 also has been shown to lead to acute kidney injury (AKI) through both direct and indirect mechanisms. The incidence of COVID-19 AKI has been decreasing as the pandemic has evolved, but continues to be associated with adverse patient outcomes correlating with the severity of AKI. There is also increasing evidence examining the longer-term effect of COVID-19 on the kidney demonstrating continued decline in kidney function several months after infection. This review summarizes the current evidence examining the impact of COVID-19 on the kidney, covering both the impact on patients with CKD, including patients receiving kidney replacement therapy, in addition to discussing COVID-19 AKI.<br/

The interaction of class and gender in illness narratives

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2008 BSA Publications Ltd.Perspectives on gender and identity that emphasize variability of performance, local context and individual agency have displaced earlier paradigms.These are now perceived to have supported gender stereotypes and language ideologies by emphasizing gender difference and homogeneity within genders. In a secondary analysis of health and illness narratives we explore the interaction of class and gender in individuals' constructions of gendered identity. High social class men perform gender in particularly varied ways and we speculate that this variable repertoire, including the use of what was once termed `women's language', is linked to a capacity to maintain social distinction and authority. Men's performance of conventional masculinity is often threatened by both the experience of illness and being interviewed about personal experience. Lower social class women in particular demonstrate an intensification of a pre-existing informal family and support group culture, marking successful members by awarding them the accolade of being `lovely'.ESR

Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial

Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs). Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results: In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers. Conclusions: Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs

The structure of a potassium-selective ion channel reveals a hydrophobic gate regulating ion permeation

Protein dynamics are essential to function. One example of this is the various gating mechanisms within ion channels, which are transmembrane proteins that act as gateways into the cell. Typical ion channels switch between an open and closed state via a conformational transition which is often triggered by an external stimulus, such as ligand binding or pH and voltage differences. The atomic resolution structure of a potassium-selective ion channel named NaK2K has allowed us to observe that a hydro­phobic residue at the bottom of the selectivity filter, Phe92, appears in dual conformations. One of the two conformations of Phe92 restricts the diameter of the exit pore around the selectivity filter, limiting ion flow through the channel, while the other conformation of Phe92 provides a larger-diameter exit pore from the selectivity filter. Thus, it can be concluded that Phe92 acts as a hydro­phobic gate, regulating the flow of ions through the selectivity filter

Quantum deformations of associative algebras and integrable systems

Quantum deformations of the structure constants for a class of associative noncommutative algebras are studied. It is shown that these deformations are governed by the quantum central systems which has a geometrical meaning of vanishing Riemann curvature tensor for Christoffel symbols identified with the structure constants. A subclass of isoassociative quantum deformations is described by the oriented associativity equation and, in particular, by the WDVV equation. It is demonstrated that a wider class of weakly (non)associative quantum deformations is connected with the integrable soliton equations too. In particular, such deformations for the three-dimensional and infinite-dimensional algebras are described by the Boussinesq equation and KP hierarchy, respectively.Comment: Numeration of the formulas is correcte

The Labour Government, the Treasury and the £6 pay policy of July 1975

The 1974-79 Labour Government was elected in a climate of opinion that was fiercely opposed to government intervention in the wage determination process, and was committed to the principles of free collective bargaining in its manifestoes. However, by December 1974 the Treasury was advocating a formal incomes policy, and by July 1975 the government had introduced a £6 flat rate pay norm. With reference to archival sources, the paper demonstrates that TUC and Labour Party opposition to incomes policy was reconciled with the Treasury's advocacy by limiting the Bank of England‟s intervention in the foreign exchange market when sterling came under pressure. This both helped to achieve the Treasury's objective of improving the competitiveness of British industry, and acted as a catalyst for the introduction of incomes policy because the slide could be attributed to a lack of market confidence in British counter-inflation policy